Generic placeholder image

Current Pharmaceutical Design


ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Mini-Review Article

Experimental and Clinical Evidence of Endothelial Dysfunction in Inflammatory Bowel Disease

Author(s): Mariana Ferreira-Duarte, Joana Beatriz Sousa, Carmen Diniz, Teresa Sousa, Margarida Duarte-Araújo and Manuela Morato*

Volume 26, Issue 30, 2020

Page: [3733 - 3747] Pages: 15

DOI: 10.2174/1381612826666200701212414

Price: $65


The endothelium has a crucial role in proper hemodynamics. Inflammatory bowel disease (IBD) is mainly a chronic inflammatory condition of the gastrointestinal tract. However, considerable evidence points to high cardiovascular risk in patients with IBD. This review positions the basic mechanisms of endothelial dysfunction in the IBD setting (both clinical and experimental). Furthermore, we review the main effects of drugs used to treat IBD in endothelial (dys)function. Moreover, we leave challenging points for enlarging the therapeutic arsenal for IBD with new or repurposed drugs that target endothelial dysfunction besides inflammation.

Keywords: Inflammatory Bowel Disease, endothelium dysfunction, experimental and clinical studies, hemodynamics, cardiovascular, IBD.

Bermejo-Martin JF, Martín-Fernandez M, López-Mestanza C, Duque P, Almansa R. Shared features of endothelial dysfunction between sepsis and its preceding risk factors (Aging and Chronic Disease). J Clin Med 2018; 7(11): 7.
[] [PMID: 30380785]
Radeva MY, Waschke J. Mind the gap: mechanisms regulating the endothelial barrier. Acta Physiol (Oxf) 2018; 222(1): 222.
[] [PMID: 28231640]
Martin L, Koczera P, Zechendorf E, Schuerholz T. the endothelial glycocalyx: new diagnostic and therapeutic approaches in sepsis. BioMed Res Int 2016; 2016: 3758278.
[] [PMID: 27699168]
Kolářová H, Ambrůzová B, Svihálková Šindlerová L, Klinke A, Kubala L. Modulation of endothelial glycocalyx structure under inflammatory conditions. Mediators Inflamm 2014; 2014: 694312.
[] [PMID: 24803742]
McCarron JG, Lee MD, Wilson C. The Endothelium Solves Problems That Endothelial Cells Do Not Know Exist. Trends Pharmacol Sci 2017; 38: 322-38.
Rajendran P, Rengarajan T, Thangavel J, et al. The vascular endothelium and human diseases. Int J Biol Sci 2013; 9(10): 1057-69.
[] [PMID: 24250251]
Rubanyi GM. Endothelium-derived relaxing and contracting factors. J Cell Biochem 1991; 46(1): 27-36.
[] [PMID: 1874796]
Joana Sousa CD. Vascular Sysmpathetic Neurotransmission and endothelial dysfunction. Endothelial dysfunction - old concepts and new challenges. 2017.
Somoza B, González MC, González JM, Abderrahim F, Arribas SM, Fernández-Alfonso MS. Modulatory role of the adventitia on noradrenaline and angiotensin II responses role of endothelium and AT2 receptors. Cardiovasc Res 2005; 65(2): 478-86.
[] [PMID: 15639487]
Sousa JB, Vieira-Rocha MS, Arribas SM, González MC, Fresco P, Diniz C. Endothelial and neuronal nitric oxide activate distinct pathways on sympathetic neurotransmission in rat tail and mesenteric arteries. PLoS One 2015; 10(6): e0129224.
[] [PMID: 26075386]
Sousa JB, Fresco P, Diniz C. Endothelial dysfunction impairs vascular neurotransmission in tail arteries. Neurochem Int 2015; 80: 7-13.
[] [PMID: 25447765]
Moncada S, Palmer RM, Higgs EA. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev 1991; 43(2): 109-42.
[PMID: 1852778]
Török J. Participation of nitric oxide in different models of experimental hypertension. Physiol Res 2008; 57(6): 813-25.
[PMID: 19154086]
Vanhoutte PM. Endothelial dysfunction: the first step toward coronary arteriosclerosis. Circ J 2009; 73(4): 595-601.
[] [PMID: 19225203]
Vanhoutte PM, Shimokawa H, Tang EH, Feletou M. Endothelial dysfunction and vascular disease. Acta Physiol (Oxf) 2009; 196(2): 193-222.
[] [PMID: 19220204]
Westcott EB, Segal SS. Perivascular innervation: a multiplicity of roles in vasomotor control and myoendothelial signaling. Microcirculation 2013; 20(3): 217-38.
[] [PMID: 23289720]
Olmos L, Mombouli JV, Illiano S, Vanhoutte PM. cGMP mediates the desensitization to bradykinin in isolated canine coronary arteries. Am J Physiol 1995; 268(2 Pt 2): H865-70.
[PMID: 7864213]
Fernández-Alfonso MS, González C. Nitric oxide and the reninangiotensin system. Is there a physiological interplay between the systems? J Hypertens 1999; 17(10): 1355-61.
[] [PMID: 10526894]
Facemire CS, Nixon AB, Griffiths R, Hurwitz H, Coffman TM. Vascular endothelial growth factor receptor 2 controls blood pressure by regulating nitric oxide synthase expression. Hypertension 2009; 54(3): 652-8.
[] [PMID: 19652084]
Hou HH, Hammock BD, Su KH, et al. N-terminal domain of soluble epoxide hydrolase negatively regulates the VEGF-mediated activation of endothelial nitric oxide synthase. Cardiovasc Res 2012; 93(1): 120-9.
[] [PMID: 22072631]
Skinner M, Philp K, Lengel D, et al. The contribution of VEGF signalling to fostamatinib-induced blood pressure elevation. Br J Pharmacol 2014; 171(9): 2308-20.
[] [PMID: 24329544]
Félétou M, Vanhoutte PM. Endothelial dysfunction: a multifaceted disorder (The Wiggers Award Lecture). Am J Physiol Heart Circ Physiol 2006; 291(3): H985-H1002.
[] [PMID: 16632549]
van der Vorm LN, Remijn JA, de Laat B, Huskens D. Effects of Plasmin on von Willebrand Factor and Platelets: A Narrative Review. TH Open 2018; 2(2): e218-28.
[] [PMID: 31249945]
Kappers MH, de Beer VJ, Zhou Z, et al. Sunitinib-induced systemic vasoconstriction in swine is endothelin mediated and does not involve nitric oxide or oxidative stress. Hypertension 2012; 59(1): 151-7.
[] [PMID: 22124432]
Lankhorst S, Kappers MH, van Esch JH, Danser AH, van den Meiracker AH. Hypertension during vascular endothelial growth factor inhibition: focus on nitric oxide, endothelin-1, and oxidative stress. Antioxid Redox Signal 2014; 20(1): 135-45.
[] [PMID: 23458507]
Konukoglu D, Uzun H. Endothelial dysfunction and hypertension. Adv Exp Med Biol 2017; 956: 511-40.
[] [PMID: 28035582]
Gryglewski RJ, Uracz W, Chłopicki S, Marcinkiewicz E. Bradykinin as a major endogenous regulator of endothelial function. Pediatr Pathol Mol Med 2002; 21(3): 279-90.
[] [PMID: 12056503]
Vanhoutte PM, Mombouli JV. Vascular endothelium: vasoactive mediators. Prog Cardiovasc Dis 1996; 39(3): 229-38.
[] [PMID: 8970575]
Tejero J, Shiva S, Gladwin MT. sources of vascular nitric oxide and reactive oxygen species and their regulation. Physiol Rev 2019; 99(1): 311-79.
[] [PMID: 30379623]
Rojas E, Rodríguez-Molina D, Bolli P, et al. The role of adiponectin in endothelial dysfunction and hypertension. Curr Hypertens Rep 2014; 16(8): 463.
[] [PMID: 24924994]
Vásquez-Vivar J. Tetrahydrobiopterin, superoxide, and vascular dysfunction. Free Radic Biol Med 2009; 47(8): 1108-19.
[] [PMID: 19628033]
Kim YW, Byzova TV. Oxidative stress in angiogenesis and vascular disease. Blood 2014; 123(5): 625-31.
[] [PMID: 24300855]
Brownlee M. The pathobiology of diabetic complications: a unifying mechanism. Diabetes 2005; 54(6): 1615-25.
[] [PMID: 15919781]
Nightingale T, Cutler D. The secretion of von Willebrand factor from endothelial cells; an increasingly complicated story. J Thromb Haemost 2013; 11(Suppl. 1): 192-201.
[] [PMID: 23809123]
Sibal L, Agarwal SC, Home PD, Boger RH. The role of asymmetric dimethylarginine (adma) in endothelial dysfunction and cardiovascular disease. Curr Cardiol Rev 2010; 6(2): 82-90.
[] [PMID: 21532773]
Liao JK. Linking endothelial dysfunction with endothelial cell activation. J Clin Invest 2013; 123(2): 540-1.
[] [PMID: 23485580]
Lee W, Ku SK, Kim SW, Bae JS. Endocan elicits severe vascular inflammatory responses in vitro and in vivo. J Cell Physiol 2014; 229(5): 620-30.
[] [PMID: 24446198]
Béchard D, Scherpereel A, Hammad H, et al. Human endothelial-cell specific molecule-1 binds directly to the integrin CD11a/CD18 (LFA-1) and blocks binding to intercellular adhesion molecule-1. J Immunol 2001; 167(6): 3099-106.
[] [PMID: 11544294]
Chen CA, Wang TY, Varadharaj S, et al. S-glutathionylation uncouples eNOS and regulates its cellular and vascular function. Nature 2010; 468(7327): 1115-8.
[] [PMID: 21179168]
Daiber A, Steven S, Weber A, et al. Targeting vascular (endothelial) dysfunction. Br J Pharmacol 2017; 174(12): 1591-619.
[] [PMID: 27187006]
Luz PLD, Libby P, Chagas ACP, Laurindo FRM. Endothelium and cardiovascular diseases vascular biology and clinical syndromes. Elsevier 2018.
Owczarek D, Cibor D, Mach T. Asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), arginine, and 8- iso-prostaglandin F2alpha (8-iso-PGF2alpha) level in patients with inflammatory bowel diseases. Inflamm Bowel Dis 2010; 16(1): 52-7.
[] [PMID: 19575355]
R.- CM, Sousa T, Gomes P. Role of oxidative stress in the pathophysiology of arterial hypertension and heart failure.DN Chakraborti S, Ganguly N, Dikshit M (Ed). Oxidative Stress in Heart Diseases . Springer, Singapore 2019; pp. 509-37.
Al-Soudi A, Kaaij MH, Tas SW. Endothelial cells: From innocent bystanders to active participants in immune responses. Autoimmun Rev 2017; 16(9): 951-62.
[] [PMID: 28698091]
RR, Yuan SY. Signaling mechanisms in the regulation of endothelial permeability.regulation of endothelial barrier function.Sciences MCL. Ed.. San Rafael, CA 2010.
G.D. Kvietysvi P. Mediators and mechanisms of the in-creased blood flow, vascular permeability, and blood vessel proliferation in inflamed tissue. MR McManus LM (Ed). Pathobiology of Human Disease 2014; 244-57.
Winn RK, Harlan JM. The role of endothelial cell apoptosis in inflammatory and immune diseases. J Thromb Haemost 2005; 3(8): 1815-24.
[] [PMID: 16102048]
Sturtzel C. Endothelial cells. Adv Exp Med Biol 2017; 1003: 71-91.
[] [PMID: 28667554]
Szekanecz Z, Koch AE. Mechanisms of disease: angiogenesis in inflammatory diseases. Nat Clin Pract Rheumatol 2007; 3(11): 635-43.
[] [PMID: 17968334]
Cromer WE, Mathis JM, Granger DN, Chaitanya GV, Alexander JS. Role of the endothelium in inflammatory bowel diseases. World J Gastroenterol 2011; 17(5): 578-93.
[] [PMID: 21350707]
Watson T, Goon PK, Lip GY. Endothelial progenitor cells, endothelial dysfunction, inflammation, and oxidative stress in hypertension. Antioxid Redox Signal 2008; 10(6): 1079-88.
[] [PMID: 18315493]
Kalinowski L, Malinski T. Endothelial NADH/NADPH-dependent enzymatic sources of superoxide production: relationship to endothelial dysfunction. Acta Biochim Pol 2004; 51(2): 459-69.
[] [PMID: 15218542]
Lin CP, Lin FY, Huang PH, et al. Endothelial progenitor cell dysfunction in cardiovascular diseases: role of reactive oxygen species and inflammation. BioMed Res Int 2013; 2013: 845037
[] [PMID: 23484163]
Werner N, Kosiol S, Schiegl T, et al. Circulating endothelial progenitor cells and cardiovascular outcomes. N Engl J Med 2005; 353(10): 999-1007.
[] [PMID: 16148285]
Hill JM, Zalos G, Halcox JP, et al. Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. N Engl J Med 2003; 348(7): 593-600.
[] [PMID: 12584367]
Steyers CM III, Miller FJ Jr. Endothelial dysfunction in chronic inflammatory diseases. Int J Mol Sci 2014; 15(7): 11324-49.
[] [PMID: 24968272]
Verhamme P, Hoylaerts MF. The pivotal role of the endothelium in haemostasis and thrombosis. Acta Clin Belg 2006; 61(5): 213-9.
[] [PMID: 17240734]
Ng SC, Shi HY, Hamidi N, et al. Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies. Lancet 2018; 390(10114): 2769-78.
[] [PMID: 29050646]
Strohl M, Gonczi L, Kurt Z, Bessissow T, Lakatos PL. Quality of care in inflammatory bowel diseases: What is the best way to better outcomes? World J Gastroenterol 2018; 24(22): 2363-72.
[] [PMID: 29904243]
Ramos A, Calvet X, Sicilia B, et al. IBD-related work disability in the community: Prevalence, severity and predictive factors. A cross-sectional study. United European Gastroenterol J 2015; 3(4): 335-42.
[] [PMID: 26279841]
Kaser A, Zeissig S, Blumberg RS. Inflammatory bowel disease. Annu Rev Immunol 2010; 28: 573-621.
[] [PMID: 20192811]
Martini E, Krug SM, Siegmund B, Neurath MF, Becker C. mend your fences: the epithelial barrier and its relationship with mucosal immunity in inflammatory bowel disease. Cell Mol Gastroenterol Hepatol 2017; 4(1): 33-46.
[] [PMID: 28560287]
Geremia A, Biancheri P, Allan P, Corazza GR, Di Sabatino A. Innate and adaptive immunity in inflammatory bowel disease. Autoimmun Rev 2014; 13(1): 3-10.
[] [PMID: 23774107]
Maloy KJ, Powrie F. Intestinal homeostasis and its breakdown in inflammatory bowel disease. Nature 2011; 474(7351): 298-306.
[] [PMID: 21677746]
Hatoum OA, Binion DG. The vasculature and inflammatory bowel disease: contribution to pathogenesis and clinical pathology. Inflamm Bowel Dis 2005; 11(3): 304-13.
[] [PMID: 15735437]
Nevulis MG, Baker C, Lebovics E, Frishman WH. Overview of link between inflammatory bowel disease and cardiovascular disease. Cardiol Rev 2018; 26: 287-93.
Sun HH, Tian F. Inflammatory bowel disease and cardiovascular disease incidence and mortality: A meta-analysis. Eur J Prev Cardiol 2018; 25(15): 1623-31.
[] [PMID: 30074405]
Keller JJ, Wang J, Hwang YL, et al. Increased risk of stroke among patients with Crohn’s disease: a population-based matched cohort study. Int J Colorectal Dis 2015; 30(5): 645-53.
[] [PMID: 25608496]
Danese S. Inflammation and the mucosal microcirculation in inflammatory bowel disease: the ebb and flow. Curr Opin Gastroenterol 2007; 23(4): 384-9.
[] [PMID: 17545773]
Ma MY, Xu XH, Luo B, et al. Immunohistochemical study on myocardial acute ischemia reperfusion injury in rats with anti-FOS protein antibody. Fa Yi Xue Za Zhi 1999; 15: 193-195, 254.
He Z, Si Y, Jiang T, et al. Phosphotidylserine exposure and neutrophil extracellular traps enhance procoagulant activity in patients with inflammatory bowel disease. Thromb Haemost 2016; 115(4): 738-51.
[] [PMID: 26660948]
Binion DG, West GA, Ina K, Ziats NP, Emancipator SN, Fiocchi C. Enhanced leukocyte binding by intestinal microvascular endothelial cells in inflammatory bowel disease. Gastroenterology 1997; 112(6): 1895-907.
[] [PMID: 9178682]
Cibor D, Domagala-Rodacka R, Rodacki T, Jurczyszyn A, Mach T, Owczarek D. Endothelial dysfunction in inflammatory bowel diseases: Pathogenesis, assessment and implications. World J Gastroenterol 2016; 22(3): 1067-77.
[] [PMID: 26811647]
Roifman I, Sun YC, Fedwick JP, et al. Evidence of endothelial dysfunction in patients with inflammatory bowel disease. Clin Gastroenterol Hepatol 2009; 7(2): 175-82.
[] [PMID: 19121648]
Hatoum OA, Binion DG, Otterson MF, Gutterman DD. Acquired microvascular dysfunction in inflammatory bowel disease: Loss of nitric oxide-mediated vasodilation. Gastroenterology 2003; 125(1): 58-69.
[] [PMID: 12851871]
Kocaman O, Sahin T, Aygun C, Senturk O, Hulagu S. Endothelial dysfunction in patients with ulcerative colitis. Inflamm Bowel Dis 2006; 12(3): 166-71.
[] [PMID: 16534416]
Fumery M, Xiaocang C, Dauchet L, Gower-Rousseau C, Peyrin-Biroulet L, Colombel JF. Thromboembolic events and cardiovascular mortality in inflammatory bowel diseases: a meta-analysis of observational studies. J Crohn’s Colitis 2014; 8(6): 469-79.
[] [PMID: 24183231]
Zanoli L, Inserra G, Castellino P. Increased cardiovascular risk in subjects with a low prevalence of classic cardiovascular risk factors: The inflammatory bowel disease paradox. Trends Cardiovasc Med 2015; 25(8): 705-6.
[] [PMID: 25952369]
Papa A, Danese S, Urgesi R, et al. Early atherosclerosis in patients with inflammatory bowel disease. Eur Rev Med Pharmacol Sci 2006; 10(1): 7-11.
[PMID: 16494104]
Ozturk K, Guler AK, Cakir M, et al. pulse wave velocity, intima media thickness, and flow-mediated dilatation in patients with normotensive normogly-cemic inflammatory bowel disease. Inflamm Bowel Dis 2015; 21: 1314-20.
Aloi M, Tromba L, Di Nardo G, et al. Premature subclinical atherosclerosis in pediatric inflammato-ry bowel disease. J Pediatr 2012; 161: 589-94.
Aloi M, Tromba L, Rizzo V, et al. Aortic Intima-media thickness as an early marker of atherosclerosis in children with inflammatory bowel disease. J Pediatr Gastroenterol Nutr 2015; 61(1): 41-6.
[] [PMID: 26039941]
Lakatta EG, Levy D. Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises: Part I: aging arteries: a “set up” for vascular disease. Circulation 2003; 107(1): 139-46.
[] [PMID: 12515756]
Dart AM, Kingwell BA. Pulse pressure--a review of mechanisms and clinical relevance. J Am Coll Cardiol 2001; 37(4): 975-84.
[] [PMID: 11263624]
Palombo C, Kozakova M. Arterial stiffness, atherosclerosis and cardiovascular risk: Pathophysiologic mechanisms and emerging clinical indications. Vascul Pharmacol 2016; 77: 1-7.
[] [PMID: 26643779]
Hansen L, Taylor WR. Is increased arterial stiffness a cause or consequence of atherosclerosis? Atherosclerosis 2016; 249: 226-7.
[] [PMID: 27133480]
Zanoli L, Rastelli S, Granata A, et al. Arterial stiffness in inflammatory bowel disease: a systematic review and meta-analysis. J Hypertens 2016; 34(5): 822-9.
[] [PMID: 26882040]
Magro F, Soares JB, Fernandes D. Venous thrombosis and prothrombotic factors in inflammatory bowel disease. World J Gastroenterol 2014; 20(17): 4857-72.
[] [PMID: 24803797]
Prijić R, Premužić V, Brinar M, Krznarić Ž, Jelaković B, Čuković-Čavka S. Increased arterial stiffness - similar findings in patients with inflammatory bowel disease without prior hypertension or diabetes and in patients with well-controlled hypertension. Blood Press 2018; 27(4): 240-6.
[] [PMID: 29790793]
Gimbrone MA Jr, García-Cardeña G. endothelial cell dysfunction and the pathobiology of atherosclerosis. Circ Res 2016; 118(4): 620-36.
[] [PMID: 26892962]
Hansson GK. Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med 2005; 352(16): 1685-95.
[] [PMID: 15843671]
Mäki-Petäjä KM, Wilkinson IB. Anti-inflammatory drugs and statins for arterial stiffness reduction. Curr Pharm Des 2009; 15(3): 290-303.
[] [PMID: 19149619]
Fan F, Galvin A, Fang L, et al. Comparison of inflammation, arterial stiffness and traditional cardiovascular risk factors between rheumatoid arthritis and inflammatory bowel disease. J Inflamm (Lond) 2014; 11(1): 29.
[] [PMID: 25337037]
D’Alessio S, Tacconi C, Fiocchi C, Danese S. Advances in therapeutic interventions targeting the vascular and lymphatic endothelium in inflammatory bowel disease. Curr Opin Gastroenterol 2013; 29(6): 608-13.
[] [PMID: 24100721]
Hatoum OA, Miura H, Binion DG. The vascular contribution in the pathogenesis of inflammatory bowel disease. Am J Physiol Heart Circ Physiol 2003; 285(5): H1791-6.
[] [PMID: 14561675]
Charo IF, Ransohoff RM. The many roles of chemokines and chemokine receptors in inflammation. N Engl J Med 2006; 354(6): 610-21.
[] [PMID: 16467548]
Danese S. Role of the vascular and lymphatic endothelium in the pathogenesis of inflammatory bowel disease: ‘brothers in arms’. Gut 2011; 60(7): 998-1008.
[] [PMID: 21212253]
Deban L, Correale C, Vetrano S, Malesci A, Danese S. Multiple pathogenic roles of microvasculature in inflammatory bowel disease: a Jack of all trades. Am J Pathol 2008; 172(6): 1457-66.
[] [PMID: 18458096]
Gravina AG, Dallio M, Masarone M, et al. Vascular endothelial dysfunction in inflammatory bowel diseases: pharmacological and nonpharmacological targets. Oxid Med Cell Longev 2018; 2018: 2568569
[] [PMID: 29849875]
Kawachi S, Jennings S, Panes J, et al. Cytokine and endothelial cell adhesion molecule expression in interleukin-10-deficient mice. Am J Physiol Gastrointest Liver Physiol 2000; 278(5): G734-43.
[] [PMID: 10801266]
Sans M, Fuster D, Vázquez A, et al. 123Iodine-labelled anti-VCAM-1 antibody scintigraphy in the assessment of experimental colitis. Eur J Gastroenterol Hepatol 2001; 13(1): 31-8.
[] [PMID: 11204806]
Soriano A, Salas A, Salas A, et al. VCAM-1, but not ICAM-1 or MAdCAM-1, immunoblockade ameliorates DSS-induced colitis in mice. Lab Invest 2000; 80(10): 1541-51.
[] [PMID: 11045571]
Therrien A, Chapuy L, Bsat M, et al. Recruitment of activated neutrophils correlates with disease severity in adult Crohn’s disease. Clin Exp Immunol 2019; 195(2): 251-64.
[] [PMID: 30347439]
Briskin M, Shyjan A, Cochran N, et al. Human mucosal addressin cell adhesion molecule-1 is preferentially expressed in intestinal tract and associated lymphoid tissue. Am J Pathol 1997; 151: 97-110.
Burgio VL, Fais S, Boirivant M, Perrone A, Pallone F. Peripheral monocyte and naive T-cell recruitment and activation in Crohn’s disease. Gastroenterology 1995; 109(4): 1029-38.
[] [PMID: 7557067]
Park SC, Jeen YT. Anti-integrin therapy for inflammatory bowel disease. World J Gastroenterol 2018; 24(17): 1868-80.
[] [PMID: 29740202]
Nelson SM, Nguyen TM, McDonald JW, MacDonald JK. Natalizumab for induction of remission in Crohn’s disease. Cochrane Database Syst Rev 2018; 8: CD006097
[] [PMID: 30068022]
Picardo S, Panaccione R. Anti-MADCAM therapy for ulcerative colitis. Expert Opin Biol Ther 2019; 20(4): 437-42.
[PMID: 31709847]
Sun H, Kuk W, Rivera-Nieves J, Lopez-Ramirez MA, Eckmann L, Ginsberg MH. β7 integrin inhibition can increase intestinal inflammation by impairing homing of CD25hiFoxP3+ regulatory t cells. Cell Mol Gastroenterol Hepatol 2020; 9(3): 369-85.
[] [PMID: 31707128]
Mizushima T, Sasaki M, Ando T, et al. Blockage of angiotensin II type 1 receptor regulates TNF-alpha-induced MAdCAM-1 expression via inhibition of NF-kappaB translocation to the nucleus and ameliorates colitis. Am J Physiol Gastrointest Liver Physiol 2010; 298(2): G255-66.
[] [PMID: 19940029]
Horowitz S, Binion DG, Nelson VM, et al. Increased arginase activity and endothelial dysfunction in human inflammatory bowel disease. Am J Physiol Gastrointest Liver Physiol 2007; 292(5): G1323-36.
[] [PMID: 17218473]
Chang CI, Liao JC, Kuo L. Arginase modulates nitric oxide production in activated macrophages. Am J Physiol 1998; 274(1): H342-8.
[PMID: 9458885]
Rafiee P, Johnson CP, Li MS, et al. Cyclosporine A enhances leukocyte binding by human intestinal microvascular endothelial cells through inhibition of p38 MAPK and iNOS. Paradoxical proinflammatory effect on the microvascular endothelium. J Biol Chem 2002; 277(38): 35605-15.
[] [PMID: 12110686]
Binion DG, Fu S, Ramanujam KS, et al. iNOS expression in human intestinal microvascular endothelial cells inhibits leukocyte adhesion. Am J Physiol 1998; 275(3): G592-603.
[PMID: 9724273]
Binion DG, Rafiee P, Ramanujam KS, et al. Deficient iNOS in inflammatory bowel disease intestinal microvascular endothelial cells results in increased leukocyte adhesion. Free Radic Biol Med 2000; 29(9): 881-8.
[] [PMID: 11063913]
Singer II II, Kawka DW, Scott S, et al. Expression of inducible nitric oxide synthase and nitrotyrosine in colonic epithelium in inflammatory bowel disease. Gastroenterology 1996; 111(4): 871-85.
[] [PMID: 8831582]
Kimura H, Hokari R, Miura S, et al. Increased expression of an inducible isoform of nitric oxide synthase and the formation of peroxynitrite in colonic mucosa of patients with active ulcerative colitis. Gut 1998; 42(2): 180-7.
[] [PMID: 9536941]
Förstermann U. Janus-faced role of endothelial NO synthase in vascular disease: uncoupling of oxygen reduction from NO synthesis and its pharmacological reversal. Biol Chem 2006; 387(12): 1521-33.
[] [PMID: 17132097]
V. Z, Altorjay I, Serfozo Z, Bacskai I, et al. An-ti-TNF-alpha antibody (infliximab) therapy supports the re-covery of eNOS and VEGFR2 protein expression in endothelial cells. Internation J Immunopathol Pharmacol 2011; 24: 323-35.
Sasaki M, Bharwani S, Jordan P, et al. Increased disease activity in eNOS-deficient mice in experimental colitis. Free Radic Biol Med 2003; 35(12): 1679-87.
[] [PMID: 14680690]
Oshima T, Jordan P, Grisham MB, et al. TNF-alpha induced endothelial MAdCAM-1 expression is regulated by exogenous, not endogenous nitric oxide. BMC Gastroenterol 2001; 1: 5.
[] [PMID: 11481030]
Koutroubakis IE, Tsiolakidou G, Karmiris K, Kouroumalis EA. Role of angiogenesis in inflammatory bowel disease. Inflamm Bowel Dis 2006; 12(6): 515-23.
[] [PMID: 16775497]
Eder P, Korybalska K, Linke K, Witowski J. Angiogenesis-related proteins--their role in the pathogenesis and treatment of inflammatory bowel disease. Curr Protein Pept Sci 2015; 16(3): 249-58.
[] [PMID: 25707471]
Danese S, Sans M, de la Motte C, et al. Angiogenesis as a novel component of inflammatory bowel disease pathogenesis. Gastroenterology 2006; 130(7): 2060-73.
[] [PMID: 16762629]
Danese S, Sans M, Spencer DM, et al. Angiogenesis blockade as a new therapeutic approach to experimental colitis. Gut 2007; 56(6): 855-62.
[] [PMID: 17170016]
Knod JL, Crawford K, Dusing M, Collins MH, Chernoguz A, Frischer JS. Angiogenesis and vascular endothelial growth factor-a expression associated with inflammation in pediatric Crohn’s disease. J Gastrointest Surg 2016; 20(3): 624-30.
[] [PMID: 26530519]
Quillin SP, Siegel MJ. Gastrointestinal inflammation in children: color Doppler ultrasonography. J Ultrasound Med 1994; 13(10): 751-6.
[] [PMID: 7823336]
Spalinger J, Patriquin H, Miron MC, et al. Doppler US in patients with crohn disease: vessel density in the diseased bowel reflects disease activity. Radiology 2000; 217(3): 787-91.
[] [PMID: 11110944]
Saito S, Tsuno NH, Sunami E, et al. Expression of platelet-derived endothelial cell growth factor in inflammatory bowel disease. J Gastroenterol 2003; 38(3): 229-37.
[] [PMID: 12673445]
Tian Y, Zheng Y, Teng G, Li J, Wang H. Imbalanced mucosal microcirculation in the remission stage of ulcerative colitis using probe-based confocal laser endomicroscopy. BMC Gastroenterol 2019; 19(1): 114.
[] [PMID: 31262270]
Magro F, Araujo F, Pereira P, Meireles E, Diniz-Ribeiro M, Velosom FT. Soluble selectins, sICAM, sVCAM, and angiogenic proteins in different activity groups of patients with inflammatory bowel disease. Dig Dis Sci 2004; 49(7-8): 1265-74.
[] [PMID: 15387356]
Kapsoritakis A, Sfiridaki A, Maltezos E, et al. Vascular endothelial growth factor in inflammatory bowel disease. Int J Colorectal Dis 2003; 18(5): 418-22.
[] [PMID: 12761641]
deZoeten EF, Battista KD, Colson SB, et al. Markers of hypoxia correlate with histologic and endoscopic severity of colitis in inflammatory bowel disease. Hypoxia (Auckl) 2020; 8: 1-12.
[] [PMID: 32104717]
Frysz-Naglak D, Fryc B, Klimacka-Nawrot E, et al. Expression, localization and systemic concentration of vascular endothelial growth factor (VEGF) and its receptors in patients with ulcerative colitis. Int Immunopharmacol 2011; 11(2): 220-5.
[] [PMID: 21115119]
Kanazawa S, Tsunoda T, Onuma E, Majima T, Kagiyama M, Kikuchi K. VEGF, basic-FGF, and TGF-beta in Crohn’s disease and ulcerative colitis: a novel mechanism of chronic intestinal inflammation. Am J Gastroenterol 2001; 96(3): 822-8.
[] [PMID: 11280558]
Griga T, Tromm A, Spranger J, May B. Increased serum levels of vascular endothelial growth factor in patients with inflammatory bowel disease. Scand J Gastroenterol 1998; 33(5): 504-8.
[] [PMID: 9648990]
Aksoy EK, Çetinkaya H, Savaş B, Ensari A, Torgutalp M, Efe C. Vascular endothelial growth factor, endostatin levels and clinical features among patients with ulcerative colitis and irritable bowel syndrome and among healthy controls: a cross-sectional analytical study. Sao Paulo Med J 2018; 136(6): 543-50.
[] [PMID: 30892485]
Griga T, Voigt E, Gretzer B, Brasch F, May B. Increased production of vascular endothelial growth factor by intestinal mucosa of patients with inflammatory bowel disease. Hepatogastroenterology 1999; 46(26): 920-3.
[PMID: 10370639]
Beddy D, Watson RW, Fitzpatrick JM, O’Connell PR. Increased vascular endothelial growth factor production in fibroblasts isolated from strictures in patients with Crohn’s disease. Br J Surg 2004; 91(1): 72-7.
[] [PMID: 14716797]
D’Alessio S, Correale C, Tacconi C, et al. VEGF-C-dependent stimulation of lymphatic function ameliorates experimental inflammatory bowel disease. J Clin Invest 2014; 124(9): 3863-78.
[] [PMID: 25105363]
Kadono T, Kikuchi K, Kubo M, Fujimoto M, Tamaki K. Serum concentrations of basic fibroblast growth factor in collagen diseases. J Am Acad Dermatol 1996; 35(3 Pt 1): 392-7.
[] [PMID: 8784275]
Bousvaros A, Zurakowski D, Fishman SJ, et al. Serum basic fibroblast growth factor in pediatric Crohn’s disease. Implications for wound healing. Dig Dis Sci 1997; 42(2): 378-86.
[] [PMID: 9052523]
Matsuno M, Shiota G, Umeki K, Kawasaki H, Kojo H, Miura K. Induction of plasma hepatocyte growth factor in acute colitis of mice. Inflamm Res 1997; 46(5): 166-7.
[] [PMID: 9197986]
Ortega-Cava CF, Ishihara S, Kawashima K, et al. Hepatocyte growth factor expression in dextran sodium sulfate-induced colitis in rats. Dig Dis Sci 2002; 47(10): 2275-85.
[] [PMID: 12395901]
Itoh H, Naganuma S, Takeda N, et al. Regeneration of injured intestinal mucosa is impaired in hepatocyte growth factor activator-deficient mice. Gastroenterology 2004; 127(5): 1423-35.
[] [PMID: 15521012]
Tahara Y, Ido A, Yamamoto S, et al. Hepatocyte growth factor facilitates colonic mucosal repair in experimental ulcerative colitis in rats. J Pharmacol Exp Ther 2003; 307(1): 146-51.
[] [PMID: 12954797]
Ohda Y, Hori K, Tomita T, et al. Effects of hepatocyte growth factor on rat inflammatory bowel disease models. Dig Dis Sci 2005; 50(5): 914-21.
[] [PMID: 15906768]
Numata M, Ido A, Moriuchi A, et al. Hepatocyte growth factor facilitates the repair of large colonic ulcers in 2,4,6-trinitrobenzene sulfonic acid-induced colitis in rats. Inflamm Bowel Dis 2005; 11(6): 551-8.
[] [PMID: 15905702]
Oh K, Iimuro Y, Takeuchi M, et al. Ameliorating effect of hepatocyte growth factor on inflammatory bowel disease in a murine model. Am J Physiol Gastrointest Liver Physiol 2005; 288(4): G729-35.
[] [PMID: 15550554]
Srivastava M, Zurakowski D, Cheifetz P, Leichtner A, Bousvaros A. Elevated serum hepatocyte growth factor in children and young adults with inflammatory bowel disease. J Pediatr Gastroenterol Nutr 2001; 33(5): 548-53.
[] [PMID: 11740227]
Matsuno M, Shiota G, Umeki K, Kawasaki H, Kojo H, Miura K. Clinical evaluation of hepatocyte growth factor in patients with gastrointestinal and pancreatic diseases with special reference to inflammatory bowel disease. Res Commun Mol Pathol Pharmacol 1997; 97(1): 25-37.
[PMID: 9507565]
Sturm A, Schulte C, Schatton R, et al. Transforming growth factor-beta and hepatocyte growth factor plasma levels in patients with inflammatory bowel disease. Eur J Gastroenterol Hepatol 2000; 12(4): 445-50.
[] [PMID: 10783999]
Eliceiri BP, Cheresh DA. Role of alpha v integrins during angiogenesis. Cancer J 2000; 6(Suppl. 3): S245-9.
[PMID: 10874494]
Punekar S, Zak S, Kalter VG, et al. Thrombospondin 1 and its mimetic peptide ABT-510 decrease angiogenesis and inflammation in a murine model of inflammatory bowel disease. Pathobiology 2008; 75(1): 9-21.
[] [PMID: 18334835]
Zak S, Treven J, Nash N, Gutierrez LS. Lack of thrombospondin-1 increases angiogenesis in a model of chronic inflammatory bowel disease. Int J Colorectal Dis 2008; 23(3): 297-304.
[] [PMID: 18043928]
Voudoukis E, Karmiris K, Koutroubakis IE. Multipotent role of platelets in inflammatory bowel diseases: a clinical approach. World J Gastroenterol 2014; 20(12): 3180-90.
[] [PMID: 24696603]
Webberley MJ, Hart MT, Melikian V. Thromboembolism in inflammatory bowel disease: role of platelets. Gut 1993; 34(2): 247-51.
[] [PMID: 8432482]
Ashton JJ, Borca F, Mossotto E, Phan HTT, Ennis S, Beattie RM. Analysis and hierarchical clustering of blood results before diagnosis in pediatric inflammatory bowel disease. Inflamm Bowel Dis 2020; 26: 469-75.
Takaki Y, Mizuochi T, Eda K, Ishihara J, Yamashita Y. Laboratory values in Japanese children with newly diagnosed inflammatory bowel disease. Pediatr Int (Roma) 2019; 61(7): 720-5.
[] [PMID: 31102555]
Li T, Wang C, Liu Y, et al. Neutrophil extracellular traps induce intestinal damage and thrombotic tendency in inflammatory bowel disease. J Crohn’s Colitis 2020; 14(2): 240-53.
[] [PMID: 31325355]
Schmid W, Vogelsang H, Papay P, et al. Increased responsiveness to thrombin through protease-activated receptors (PAR)-1 and -4 in active Crohn’s disease. J Crohn’s Colitis 2014; 8(6): 495-503.
[] [PMID: 24291018]
Larsen TB, Nielsen JN, Fredholm L, et al. Platelets and anticoagulant capacity in patients with inflammatory bowel disease. Pathophysiol Haemost Thromb 2002; 32(2): 92-6.
[] [PMID: 12214155]
Andoh A, Yoshida T, Yagi Y, et al. Increased aggregation response of platelets in patients with inflammatory bowel disease. J Gastroenterol 2006; 41(1): 47-54.
[] [PMID: 16501857]
Senchenkova EY, Komoto S, Russell J, et al. Interleukin-6 mediates the platelet abnormalities and thrombogenesis associated with experimental colitis. Am J Pathol 2013; 183(1): 173-81.
[] [PMID: 23673000]
Yan SL, Russell J, Granger DN. Platelet activation and platelet-leukocyte aggregation elicited in experimental colitis are mediated by interleukin-6. Inflamm Bowel Dis 2014; 20(2): 353-62.
[] [PMID: 24390064]
Polińska B, Matowicka-Karna J, Kemona H. Assessment of the influence of the inflammatory process on the activation of blood platelets and morphological parameters in patients with ulcerative colitis (colitis ulcerosa). Folia Histochem Cytobiol 2011; 49(1): 119-24.
[] [PMID: 21526498]
Heits F, Stahl M, Ludwig D, Stange EF, Jelkmann W. Elevated serum thrombopoietin and interleukin-6 concentrations in thrombocytosis associated with inflammatory bowel disease. J Interferon Cytokine Res 1999; 19(7): 757-60.
[] [PMID: 10454346]
Gawrońska B, Matowicka-Karna J, Kralisz M, Kemona H. Markers of inflammation and influence of nitric oxide on platelet activation in the course of ulcerative colitis. Oncotarget 2017; 8(40): 68108-14.
[] [PMID: 28978100]
Petrey AC, de la Motte CA. Hyaluronan, a crucial regulator of inflammation. Front Immunol 2014; 5: 101.
[] [PMID: 24653726]
Albeiroti S, Ayasoufi K, Hill DR, Shen B, de la Motte CA. Platelet hyaluronidase-2: an enzyme that translocates to the surface upon activation to function in extracellular matrix degradation. Blood 2015; 125(9): 1460-9.
[] [PMID: 25411425]
Petrey AC, Obery DR, Kessler SP, Zawerton A, Flamion B, de la Motte CA. Platelet hyaluronidase-2 regulates the early stages of inflammatory disease in colitis. Blood 2019; 134(9): 765-75.
[] [PMID: 31262781]
van Bodegraven AA, Schoorl M, Baak JP, Linskens RK, Bartels PC, Tuynman HA. Hemostatic imbalance in active and quiescent ulcerative colitis. Am J Gastroenterol 2001; 96(2): 487-93.
[] [PMID: 11232695]
Kjeldsen J, Lassen JF, Brandslund I, Schaffalitzky de Muckadell OB. Markers of coagulation and fibrinolysis as measures of disease activity in inflammatory bowel disease. Scand J Gastroenterol 1998; 33(6): 637-43.
[] [PMID: 9669637]
Weber P, Husemann S, Vielhaber H, Zimmer KP, Nowak-Göttl U. Coagulation and fibrinolysis in children, adolescents, and young adults with inflammatory bowel disease. J Pediatr Gastroenterol Nutr 1999; 28(4): 418-22.
[] [PMID: 10204507]
Vrij AA, Rijken J, van Wersch JW, Stockbrügger RW. Coagulation and fibrinolysis in inflammatory bowel disease and in giant cell arteritis. Pathophysiol Haemost Thromb 2003; 33(2): 75-83.
[] [PMID: 14624048]
Knot E, Ten Cate JW, Leeksma OC, Tytgat GN, Vreeken J. No evidence for a prethrombotic state in stable chronic inflammatory bowel disease. J Clin Pathol 1983; 36(12): 1387-90.
[] [PMID: 6655071]
Stadnicki A. Involvement of coagulation and hemostasis in inflammatory bowel diseases. Curr Vasc Pharmacol 2012; 10(5): 659-69.
[] [PMID: 22272910]
Yilmaz S, Bayan K, Tüzün Y, Batun S, Altintaş A. A comprehensive analysis of 12 thrombophilic mutations and related parameters in patients with inflammatory bowel disease: data from Turkey. J Thromb Thrombolysis 2006; 22(3): 205-12.
[] [PMID: 17111197]
Lagrange J, Lacolley P, Wahl D, Peyrin-Biroulet L, Regnault V. Shedding light on hemostasis in patients with inflammatory bowel diseases. Clin. Gastroenterol Hepatol. 2020; S1542-3565(20): 30056-2.
[] [PMID: 31972287]
Saibeni S, Saladino V, Chantarangkul V, et al. Increased thrombin generation in inflammatory bowel diseases. Thromb Res 2010; 125(3): 278-82.
[] [PMID: 19914688]
Smith CJ, Haire WD, Kaufman SS, Mack DR. Determination of prothrombin activation fragments in young patients with inflammatory bowel disease. Am J Gastroenterol 1996; 91(6): 1221-5.
[PMID: 8651175]
Chamouard P, Grunebaum L, Wiesel ML, et al. Prothrombin fragment 1 + 2 and thrombin-antithrombin III complex as markers of activation of blood coagulation in inflammatory bowel diseases. Eur J Gastroenterol Hepatol 1995; 7(12): 1183-8.
[] [PMID: 8789309]
Alkim H, Ayaz S, Alkim C, Ulker A, Sahin B. Continuous active state of coagulation system in patients with nonthrombotic inflammatory bowel disease. Clin Appl Thromb Hemost 2011; 17(6): 600-4.
[] [PMID: 21593018]
Cibor D, Szczeklik K, Mach T, Owczarek D. Levels of tissue factor pathway inhibitor in patients with inflammatory bowel disease. Pol Arch Intern Med 2019; 129(4): 253-8.
[] [PMID: 31038478]
Kohoutova D, Pecka M, Cihak M, Cyrany J, Maly J, Bures J. Prevalence of hypercoagulable disorders in inflammatory bowel disease. Scand J Gastroenterol 2014; 49(3): 287-94.
[] [PMID: 24328909]
Bernhard H, Deutschmann A, Leschnik B, et al. Thrombin generation in pediatric patients with Crohn’s disease. Inflamm Bowel Dis 2011; 17(11): 2333-9.
[] [PMID: 21287673]
He HL, Zhang JB, Li Q. Clinical significance of expression of tissue factor and tissue factor pathway inhibitor in ulcerative colitis. World J Gastroenterol 2014; 20(23): 7461.
[] [PMID: 24966616]
Reichman-Warmusz E, Kurek J, Gabriel A, et al. Tissue hemostasis and chronic inflammation in colon biopsies of patients with inflammatory bowel disease. Pathol Res Pract 2012; 208(9): 553-6.
[] [PMID: 22842215]
Meucci G, Pareti F, Vecchi M, Saibeni S, Bressi C, de Franchis R. Serum von Willebrand factor levels in patients with inflammatory bowel disease are related to systemic inflammation. Scand J Gastroenterol 1999; 34(3): 287-90.
[] [PMID: 10232874]
Souto JC, Martínez E, Roca M, et al. Prothrombotic state and signs of endothelial lesion in plasma of patients with inflammatory bowel disease. Dig Dis Sci 1995; 40(9): 1883-9.
[] [PMID: 7555437]
Gris JC, Schved JF, Raffanel C, et al. Impaired fibrinolytic capacity in patients with inflammatory bowel disease. Thromb Haemost 1990; 63(3): 472-5.
[] [PMID: 2119529]
Saibeni S, Ciscato C, Vecchi M, et al. Antibodies to tissue-type plasminogen activator (t-PA) in patients with inflammatory bowel disease: high prevalence, interactions with functional domains of t-PA and possible implications in thrombosis. J Thromb Haemost 2006; 4(7): 1510-6.
[] [PMID: 16839347]
Koutroubakis IE, Sfiridaki A, Tsiolakidou G, Coucoutsi C, Theodoropoulou A, Kouroumalis EA. Plasma thrombin-activatable fibrinolysis inhibitor and plasminogen activator inhibitor-1 levels in inflammatory bowel disease. Eur J Gastroenterol Hepatol 2008; 20(9): 912-6.
[] [PMID: 18794606]
Owczarek D, Cibor D, Sałapa K, Głowacki MK, Mach T, Undas A. Reduced plasma fibrin clot permeability and susceptibility to lysis in patients with inflammatory bowel disease: a novel prothrombotic mechanism. Inflamm Bowel Dis 2013; 19(12): 2616-24.
[] [PMID: 24108112]
Wakefield AJ, Sawyerr AM, Dhillon AP, et al. Pathogenesis of Crohn’s disease: multifocal gastrointestinal infarction. Lancet 1989; 2(8671): 1057-62.
[] [PMID: 2572794]
Stouthard JM, Levi M, Hack CE, et al. Interleukin-6 stimulates coagulation, not fibrinolysis, in humans. Thromb Haemost 1996; 76(5): 738-42.
[] [PMID: 8950783]
Yoshida H, Russell J, Senchenkova EY, Almeida Paula LD, Granger DN. Interleukin-1beta mediates the extra-intestinal thrombosis associated with experimental colitis. Am J Pathol 2010; 177(6): 2774-81.
[] [PMID: 20971730]
Yoshida H, Yilmaz CE, Granger DN. Role of tumor necrosis factor-α in the extraintestinal thrombosis associated with colonic inflammation. Inflamm Bowel Dis 2011; 17(11): 2217-23.
[] [PMID: 21987296]
Song JW, Song KS, Choi JR, Kim SY, Rhee JH. Plasma level of IL-6 and its relationship to procoagulant and fibrinolytic markers in acute ischemic stroke. Yonsei Med J 2006; 47(2): 201-6.
[] [PMID: 16642549]
Hozumi H, Russell J, Vital S, Granger DN. IL-6 mediates the intestinal microvascular thrombosis associated with experimental colitis. Inflamm Bowel Dis 2016; 22(3): 560-8.
[] [PMID: 26818424]
Hvas CL, Bendix M, Dige A, Dahlerup JF, Agnholt J. Current, experimental, and future treatments in inflammatory bowel disease: a clinical review. Immunopharmacol Immunotoxicol 2018; 40(6): 446-60.
[] [PMID: 29745777]
Wu P, Jia F, Zhang B, Zhang P. Risk of cardiovascular disease in inflammatory bowel disease. Exp Ther Med 2017; 13(2): 395-400.
[] [PMID: 28352306]
Harbord M, Annese V, Vavricka SR, et al. European Crohn’s and Colitis Organisation. The first european evidence-based consensus on extra-intestinal manifestations in inflammatory bowel disease. J Crohn’s Colitis 2016; 10(3): 239-54.
[] [PMID: 26614685]
Moura RM, Hartmann RM, Licks F, et al. Antioxidant effect of mesalazine in the experimental colitis model induced by acetic acid. J Coloproctol (Rio J) 2016; 36: 139-48.
Rungoe C, Basit S, Ranthe MF, Wohlfahrt J, Langholz E, Jess T. Risk of ischaemic heart disease in patients with inflammatory bowel disease: a nationwide Danish cohort study. Gut 2013; 62(5): 689-94.
[] [PMID: 22961677]
Marinković G, Kroon J, Hoogenboezem M, et al. Inhibition of GTPase Rac1 in endothelium by 6-mercaptopurine results in immunosuppression in nonimmune cells: new target for an old drug. J Immunol 2014; 192(9): 4370-8.
[] [PMID: 24670805]
Marinkovic G, Hibender S, Hoogenboezem M, et al. Immunosuppressive drug azathioprine reduces aneurysm progression through inhibition of Rac1 and c-Jun-terminal-N-kinase in endothelial cells. Arterioscler Thromb Vasc Biol 2013; 33(10): 2380-8.
[] [PMID: 23950142]
dos Santos LC, Costa AV, Lopes LG, et al. Combination of azathioprine and aminosalicylate treatment prevent risk of cardiovascular disease in women with ul-cerative colitis by reducing inflammation. Med Sci Monit 2015; 21: 2305-15.
Prati C, Demougeot C, Guillot X, Godfrin-Valnet M, Wendling D. Endothelial dysfunction in joint disease. Joint Bone Spine 2014; 81(5): 386-91.
[] [PMID: 24565889]
Thornton CC, Al-Rashed F, Calay D, et al. Methotrexate-mediated activation of an AMPK-CREB-dependent pathway: a novel mechanism for vascular protection in chronic systemic inflammation. Ann Rheum Dis 2016; 75(2): 439-48.
[] [PMID: 25575725]
Bombeli T, Müller M, Straub PW, Haeberli A. Cyclosporine-induced detachment of vascular endothelial cells initiates the intrinsic coagulation system in plasma and whole blood. J Lab Clin Med 1996; 127(6): 621-34.
[] [PMID: 8648267]
Scaldaferri F, Vetrano S, Sans M, et al. VEGF-A links angiogenesis and inflammation in inflammatory bowel disease pathogenesis. Gastroenterology 2009; 136: 585-95.
Danese S, Sans M, Scaldaferri F, et al. TNF-alpha blockade down-regulates the CD40/CD40L pathway in the mucosal microcirculation: a novel anti-inflammatory mechanism of infliximab in Crohn’s disease. J Immunol 2006; 176(4): 2617-24.
[] [PMID: 16456024]
Danese S, Panés J. Development of drugs to target interactions between leukocytes and endothelial cells and treatment algorithms for in-flammatory bowel diseases. Gastroenterology 2014; 147: 981-9.
Löwenberg M, D’Haens G. Next-Generation Therapeutics for IBD. Curr Gastroenterol Rep 2015; 17(6): 21.
[] [PMID: 26031830]
Argollo M, Fiorino G, Hindryckx P, Peyrin-Biroulet L, Danese S. Novel therapeutic targets for inflammatory bowel disease. J Autoimmun 2017; 85: 103-16.
[] [PMID: 28711286]
Grenier L, Hu P. Computational drug repurposing for inflammatory bowel disease using genetic information. Comput Struct Biotechnol J 2019; 17: 127-35.
[] [PMID: 30728920]
Collij V, Festen EA, Alberts R, Weersma RK. Drug repositioning in inflammatory bowel disease based on genetic information. Inflamm Bowel Dis 2016; 22: 2562-70.
Mokry LE, Zhou S, Guo C, et al. Interleukin-18 as a drug repositioning opportunity for inflammatory bowel disease: A Mendelian randomization study. Sci Rep 2019; 9(1): 9386.
[] [PMID: 31253830]
Elhage R, Ljunggren H-G, Hansson GK. Proatherogenic role of interleukin-18: effects on inflammation and action on vascular cells: AUTHORS’ RETROSPECTIVE. Cardiovasc Res 2012; 96: 176-80.

Rights & Permissions Print Export Cite as
© 2023 Bentham Science Publishers | Privacy Policy