Generic placeholder image

Current Medicinal Chemistry


ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Review Article

Targeting the Endothelial Ca2+ Toolkit to Rescue Endothelial Dysfunction in Obesity Associated-Hypertension

Author(s): Francesco Moccia*, Sharon Negri, Pawan Faris and Roberto Berra-Romani

Volume 27 , Issue 2 , 2020

Page: [240 - 257] Pages: 18

DOI: 10.2174/0929867326666190905142135

Price: $65


Background: Obesity is a major cardiovascular risk factor which dramatically impairs endothelium- dependent vasodilation and leads to hypertension and vascular damage. The impairment of the vasomotor response to extracellular autacoids, e.g., acetylcholine, mainly depends on the reduced Nitric Oxide (NO) bioavailability, which hampers vasorelaxation in large conduit arteries. In addition, obesity may affect Endothelium-Dependent Hyperpolarization (EDH), which drives vasorelaxation in small resistance arteries and arterioles. Of note, endothelial Ca2+ signals drive NO release and trigger EDH.

Methods: A structured search of bibliographic databases was carried out to retrieve the most influential, recent articles on the impairment of vasorelaxation in animal models of obesity, including obese Zucker rats, and on the remodeling of the endothelial Ca2+ toolkit under conditions that mimic obesity. Furthermore, we searched for articles discussing how dietary manipulation could be exploited to rescue Ca2+-dependent vasodilation.

Results: We found evidence that the endothelial Ca2+ could be severely affected by obese vessels. This rearrangement could contribute to endothelial damage and is likely to be involved in the disruption of vasorelaxant mechanisms. However, several Ca2+-permeable channels, including Vanilloid Transient Receptor Potential (TRPV) 1, 3 and 4 could be stimulated by several food components to stimulate vasorelaxation in obese individuals.

Conclusion: The endothelial Ca2+ toolkit could be targeted to reduce vascular damage and rescue endothelium- dependent vasodilation in obese vessels. This hypothesis remains, however, to be probed on truly obese endothelial cells.

Keywords: Vasorelaxation, endothelium-dependent hyperpolarization (EDH), vascular damage, obese vessels, obesity, cardiovascular risk.

Aird, W.C. Endothelium in health and disease. Pharmacol. Rep., 2008, 60(1), 139-143.
[PMID: 18276995]
Goveia, J.; Stapor, P.; Carmeliet, P. Principles of targeting endothelial cell metabolism to treat angiogenesis and endothelial cell dysfunction in disease. EMBO Mol. Med., 2014, 6(9), 1105-1120.
[] [PMID: 25063693]
Moccia, F.; Guerra, G. Ca(2+) Signalling in endothelial progenitor cells: friend or foe? J. Cell. Physiol., 2016, 231(2), 314-327.
[] [PMID: 26247172]
Khazaei, M.; Moien-Afshari, F.; Laher, I. Vascular endothelial function in health and diseases. Pathophysiology, 2008, 15(1), 49-67.
[] [PMID: 18434105]
Altaany, Z.; Moccia, F.; Munaron, L.; Mancardi, D.; Wang, R. Hydrogen sulfide and endothelial dysfunction: relationship with nitric oxide. Curr. Med. Chem., 2014, 21(32), 3646-3661.
[] [PMID: 25005182]
Mancardi, D.; Pla, A.F.; Moccia, F.; Tanzi, F.; Munaron, L. Old and new gasotransmitters in the cardiovascular system: focus on the role of nitric oxide and hydrogen sulfide in endothelial cells and cardiomyocytes. Curr. Pharm. Biotechnol., 2011, 12(9), 1406-1415.
[] [PMID: 21235456]
Khaddaj Mallat, R.; Mathew John, C.; Kendrick, D.J.; Braun, A.P. The vascular endothelium: A regulator of arterial tone and interface for the immune system. Crit. Rev. Clin. Lab. Sci., 2017, 54(7-8), 458-470.
[] [PMID: 29084470]
Behringer, E.J. Calcium and electrical signaling in arterial endothelial tubes: New insights into cellular physiology and cardiovascular function. Microcirculation, 2017, 24(3)
[] [PMID: 27801542]
Garland, C.J.; Dora, K.A. EDH: endothelium-dependent hyperpolarization and microvascular signalling. Acta Physiol. (Oxf.), 2017, 219(1), 152-161.
[] [PMID: 26752699]
Moccia, F.; Berra-Romani, R.; Tanzi, F. Update on vascular endothelial Ca(2+) signalling: A tale of ion channels, pumps and transporters. World J. Biol. Chem., 2012, 3(7), 127-158.
[] [PMID: 22905291]
Adams, D.J.; Barakeh, J.; Laskey, R.; Van Breemen, C. Ion channels and regulation of intracellular calcium in vascular endothelial cells. FASEB J., 1989, 3(12), 2389-2400.
[] [PMID: 2477294]
Vanhoutte, P.M.; Tang, E.H. Endothelium-dependent contractions: when a good guy turns bad! J. Physiol., 2008, 586(22), 5295-5304.
[] [PMID: 18818246]
Perrier, E.; Fournet-Bourguignon, M.P.; Royere, E.; Molez, S.; Reure, H.; Lesage, L.; Gosgnach, W.; Frapart, Y.; Boucher, J.L.; Villeneuve, N.; Vilaine, J.P. Effect of uncoupling endothelial nitric oxide synthase on calcium homeostasis in aged porcine endothelial cells. Cardiovasc. Res., 2009, 82(1), 133-142.
[] [PMID: 19176602]
Prendergast, C.; Quayle, J.; Burdyga, T.; Wray, S. Atherosclerosis affects calcium signalling in endothelial cells from apolipoprotein E knockout mice before plaque formation. Cell Calcium, 2014, 55(3), 146-154.
[] [PMID: 24630173]
Gandhirajan, R.K.; Meng, S.; Chandramoorthy, H.C.; Mallilankaraman, K.; Mancarella, S.; Gao, H.; Razmpour, R.; Yang, X.F.; Houser, S.R.; Chen, J.; Koch, W.J.; Wang, H.; Soboloff, J.; Gill, D.L.; Madesh, M. Blockade of NOX2 and STIM1 signaling limits lipopolysaccharide-induced vascular inflammation. J. Clin. Invest., 2013, 123(2), 887-902.
[] [PMID: 23348743]
Fasanaro, P.; Magenta, A.; Zaccagnini, G.; Cicchillitti, L.; Fucile, S.; Eusebi, F.; Biglioli, P.; Capogrossi, M.C.; Martelli, F. Cyclin D1 degradation enhances endothelial cell survival upon oxidative stress. FASEB J., 2006, 20(8), 1242-1244.
[] [PMID: 16603604]
Bishara, N.B.; Ding, H. Glucose enhances expression of TRPC1 and calcium entry in endothelial cells. Am. J. Physiol. Heart Circ. Physiol., 2010, 298(1), H171-H178.
[] [PMID: 19855058]
Daskoulidou, N.; Zeng, B.; Berglund, L.M.; Jiang, H.; Chen, G.L.; Kotova, O.; Bhandari, S.; Ayoola, J.; Griffin, S.; Atkin, S.L.; Gomez, M.F.; Xu, S.Z. High glucose enhances store-operated calcium entry by upregulating ORAI/STIM via calcineurin-NFAT signalling. J. Mol. Med. (Berl.), 2015, 93(5), 511-521.
[] [PMID: 25471481]
Arruda, A.P.; Hotamisligil, G.S. Calcium homeostasis and organelle function in the pathogenesis of obesity and diabetes. Cell Metab., 2015, 22(3), 381-397.
[] [PMID: 26190652]
Carvajal, K.; Balderas-Villalobos, J.; Bello-Sanchez, M.D.; Phillips-Farfán, B.; Molina-Muñoz, T.; Aldana-Quintero, H.; Gómez-Viquez, N.L. Ca(2+) mishandling and cardiac dysfunction in obesity and insulin resistance: role of oxidative stress. Cell Calcium, 2014, 56(5), 408-415.
[] [PMID: 25168907]
Guerrero-Hernandez, A.; Verkhratsky, A. Calcium signalling in diabetes. Cell Calcium, 2014, 56(5), 297-301.
[] [PMID: 25217232]
Berridge, M.J.; Bootman, M.D.; Roderick, H.L. Calcium signalling: dynamics, homeostasis and remodelling. Nat. Rev. Mol. Cell Biol., 2003, 4(7), 517-529.
[] [PMID: 12838335]
Bootman, M.D.; Berridge, M.J.; Roderick, H.L. Calcium signalling: more messengers, more channels, more complexity. Curr. Biol., 2002, 12(16), R563-R565.
[] [PMID: 12194839]
Clapham, D.E. Calcium signaling. Cell, 2007, 131(6), 1047-1058.
[] [PMID: 18083096]
Moccia, F.; Tanzi, F.; Munaron, L. Endothelial remodelling and intracellular calcium machinery. Curr. Mol. Med., 2014, 14(4), 457-480.
[] [PMID: 24236452]
Zuccolo, E.; Lim, D.; Kheder, D.A.; Perna, A.; Catarsi, P.; Botta, L.; Rosti, V.; Riboni, L.; Sancini, G.; Tanzi, F.; D’Angelo, E.; Guerra, G.; Moccia, F. Acetylcholine induces intracellular Ca2+ oscillations and nitric oxide release in mouse brain endothelial cells. Cell Calcium, 2017, 66, 33-47.
[] [PMID: 28807148]
Radu, B.M.; Osculati, A.M.M.; Suku, E.; Banciu, A.; Tsenov, G.; Merigo, F.; Di Chio, M.; Banciu, D.D.; Tognoli, C.; Kacer, P.; Giorgetti, A.; Radu, M.; Bertini, G.; Fabene, P.F. All muscarinic acetylcholine receptors (M1-M5) are expressed in murine brain microvascular endothelium. Sci. Rep., 2017, 7(1), 5083.
[] [PMID: 28698560]
Burnstock, G. Purinergic signaling in the cardiovascular system. Circ. Res., 2017, 120(1), 207-228.
[] [PMID: 28057794]
Moccia, F.; Lodola, F.; Dragoni, S.; Bonetti, E.; Bottino, C.; Guerra, G.; Laforenza, U.; Rosti, V.; Tanzi, F. Ca2+ signalling in endothelial progenitor cells: a novel means to improve cell-based therapy and impair tumour vascularisation. Curr. Vasc. Pharmacol., 2014, 12(1), 87-105.
[] [PMID: 22724469]
Abdullaev, I.F.; Bisaillon, J.M.; Potier, M.; Gonzalez, J.C.; Motiani, R.K.; Trebak, M. Stim1 and Orai1 mediate CRAC currents and store-operated calcium entry important for endothelial cell proliferation. Circ. Res., 2008, 103(11), 1289-1299.
[] [PMID: 18845811]
Li, J.; Cubbon, R.M.; Wilson, L.A.; Amer, M.S.; McKeown, L.; Hou, B.; Majeed, Y.; Tumova, S.; Seymour, V.A.L.; Taylor, H.; Stacey, M.; O’Regan, D.; Foster, R.; Porter, K.E.; Kearney, M.T.; Beech, D.J. Orai1 and CRAC channel dependence of VEGF-activated Ca2+ entry and endothelial tube formation. Circ. Res., 2011, 108(10), 1190-1198.
[] [PMID: 21441136]
Sundivakkam, P.C.; Freichel, M.; Singh, V.; Yuan, J.P.; Vogel, S.M.; Flockerzi, V.; Malik, A.B.; Tiruppathi, C. The Ca(2+) sensor stromal interaction molecule 1 (STIM1) is necessary and sufficient for the store-operated Ca(2+) entry function of transient receptor potential canonical (TRPC) 1 and 4 channels in endothelial cells. Mol. Pharmacol., 2012, 81(4), 510-526.
[] [PMID: 22210847]
Freichel, M.; Suh, S.H.; Pfeifer, A.; Schweig, U.; Trost, C.; Weissgerber, P.; Biel, M.; Philipp, S.; Freise, D.; Droogmans, G.; Hofmann, F.; Flockerzi, V.; Nilius, B. Lack of an endothelial store-operated Ca2+ current impairs agonist-dependent vasorelaxation in TRP4-/- mice. Nat. Cell Biol., 2001, 3(2), 121-127.
[] [PMID: 11175743]
Sundivakkam, P.C.; Kwiatek, A.M.; Sharma, T.T.; Minshall, R.D.; Malik, A.B.; Tiruppathi, C. Caveolin-1 scaffold domain interacts with TRPC1 and IP3R3 to regulate Ca2+ store release-induced Ca2+ entry in endothelial cells. Am. J. Physiol. Cell Physiol., 2009, 296(3), C403-C413.
[] [PMID: 19052258]
Moccia, F.; Dragoni, S.; Lodola, F.; Bonetti, E.; Bottino, C.; Guerra, G.; Laforenza, U.; Rosti, V.; Tanzi, F. Store-dependent Ca(2+) entry in endothelial progenitor cells as a perspective tool to enhance cell-based therapy and adverse tumour vascularization. Curr. Med. Chem., 2012, 19(34), 5802-5818.
[] [PMID: 22963562]
Dragoni, S.; Laforenza, U.; Bonetti, E.; Lodola, F.; Bottino, C.; Guerra, G.; Borghesi, A.; Stronati, M.; Rosti, V.; Tanzi, F.; Moccia, F. Canonical transient receptor potential 3 channel triggers vascular endothelial growth factor-induced intracellular Ca2+ oscillations in endothelial progenitor cells isolated from umbilical cord blood. Stem Cells Dev., 2013, 22(19), 2561-2580.
[] [PMID: 23682725]
Moccia, F.; Lucariello, A.; Guerra, G. TRPC3-mediated Ca(2+) signals as a promising strategy to boost therapeutic angiogenesis in failing hearts: The role of autologous endothelial colony forming cells. J. Cell. Physiol., 2018, 233(5), 3901-3917.
[] [PMID: 28816358]
Hamdollah Zadeh, M.A.; Glass, C.A.; Magnussen, A.; Hancox, J.C.; Bates, D.O. VEGF-mediated elevated intracellular calcium and angiogenesis in human microvascular endothelial cells in vitro are inhibited by dominant negative TRPC6. Microcirculation, 2008, 15(7), 605-614.
[] [PMID: 18800249]
Gees, M.; Colsoul, B.; Nilius, B. The role of transient receptor potential cation channels in Ca2+ signaling. Cold Spring Harb. Perspect. Biol., 2010, 2(10), a003962
[] [PMID: 20861159]
Earley, S.; Brayden, J.E. Transient receptor potential channels in the vasculature. Physiol. Rev., 2015, 95(2), 645-690.
[] [PMID: 25834234]
Thakore, P.; Earley, S. Transient receptor potential channels and endothelial cell calcium signaling. Compr. Physiol., 2019, 9(3), 1249-1277.
[] [PMID: 31187891]
Ottolini, M.; Hong, K.; Sonkusare, S.K. Calcium signals that determine vascular resistance. Wiley Interdiscip. Rev. Syst. Biol. Med., 2019, 11(5), e1448
[] [PMID: 30884210]
Zuccolo, E.; Dragoni, S.; Poletto, V.; Catarsi, P.; Guido, D.; Rappa, A.; Reforgiato, M.; Lodola, F.; Lim, D.; Rosti, V.; Guerra, G.; Moccia, F. Arachidonic acid-evoked Ca2+ signals promote nitric oxide release and proliferation in human endothelial colony forming cells. Vascul. Pharmacol., 2016, 87, 159-171.
[] [PMID: 27634591]
Zheng, X.; Zinkevich, N.S.; Gebremedhin, D.; Gauthier, K.M.; Nishijima, Y.; Fang, J.; Wilcox, D.A.; Campbell, W.B.; Gutterman, D.D.; Zhang, D.X. Arachidonic acid-induced dilation in human coronary arterioles: convergence of signaling mechanisms on endothelial TRPV4-mediated Ca2+ entry. J. Am. Heart Assoc., 2013, 2(3), e000080
[] [PMID: 23619744]
Thodeti, C.K.; Matthews, B.; Ravi, A.; Mammoto, A.; Ghosh, K.; Bracha, A.L.; Ingber, D.E. TRPV4 channels mediate cyclic strain-induced endothelial cell reorientation through integrin-to-integrin signaling. Circ. Res., 2009, 104(9), 1123-1130.
[] [PMID: 19359599]
Troidl, C.; Nef, H.; Voss, S.; Schilp, A.; Kostin, S.; Troidl, K.; Szardien, S.; Rolf, A.; Schmitz-Rixen, T.; Schaper, W.; Hamm, C.W.; Elsässer, A.; Möllmann, H. Calcium-dependent signalling is essential during collateral growth in the pig hind limb-ischemia model. J. Mol. Cell. Cardiol., 2010, 49(1), 142-151.
[] [PMID: 20363225]
Watanabe, H.; Vriens, J.; Suh, S.H.; Benham, C.D.; Droogmans, G.; Nilius, B. Heat-evoked activation of TRPV4 channels in a HEK293 cell expression system and in native mouse aorta endothelial cells. J. Biol. Chem., 2002, 277(49), 47044-47051.
[] [PMID: 12354759]
Earley, S. Endothelium-dependent cerebral artery dilation mediated by transient receptor potential and Ca2+-activated K+ channels. J. Cardiovasc. Pharmacol., 2011, 57(2), 148-153.
[] [PMID: 20729757]
Berra-Romani, R.; Avelino-Cruz, J.E.; Raqeeb, A.; Della Corte, A.; Cinelli, M.; Montagnani, S.; Guerra, G.; Moccia, F.; Tanzi, F. Ca2+-dependent nitric oxide release in the injured endothelium of excised rat aorta: a promising mechanism applying in vascular prosthetic devices in aging patients. BMC Surg., 2013, 13(Suppl. 2), S40.
[] [PMID: 24266895]
Kimura, C.; Oike, M.; Ohnaka, K.; Nose, Y.; Ito, Y. Constitutive nitric oxide production in bovine aortic and brain microvascular endothelial cells: a comparative study. J. Physiol., 2004, 554(Pt 3), 721-730.
[] [PMID: 14617679]
Dedkova, E.N.; Blatter, L.A. Nitric oxide inhibits capacitative Ca2+ entry and enhances endoplasmic reticulum Ca2+ uptake in bovine vascular endothelial cells. J. Physiol., 2002, 539(Pt 1), 77-91.
[] [PMID: 11850503]
Zuccolo, E.; Laforenza, U.; Negri, S.; Botta, L.; Berra-Romani, R.; Faris, P.; Scarpellino, G.; Forcaia, G.; Pellavio, G.; Sancini, G.; Moccia, F. Muscarinic M5 receptors trigger acetylcholine-induced Ca2+ signals and nitric oxide release in human brain microvascular endothelial cells. J. Cell. Physiol., 2019, 234(4), 4540-4562.
[] [PMID: 30191989]
Lantoine, F.; Iouzalen, L.; Devynck, M.A.; Millanvoye-Van Brussel, E.; David-Dufilho, M. Nitric oxide production in human endothelial cells stimulated by histamine requires Ca2+ influx. Biochem. J., 1998, 330(Pt 2), 695-699.
[] [PMID: 9480877]
Zuccolo, E.; Kheder, D.A.; Lim, D.; Perna, A.; Nezza, F.D.; Botta, L.; Scarpellino, G.; Negri, S.; Martinotti, S.; Soda, T.; Forcaia, G.; Riboni, L.; Ranzato, E.; Sancini, G.; Ambrosone, L.; D’Angelo, E.; Guerra, G.; Moccia, F. Glutamate triggers intracellular Ca2+ oscillations and nitric oxide release by inducing NAADP- and InsP3 -dependent Ca2+ release in mouse brain endothelial cells. J. Cell. Physiol., 2019, 234(4), 3538-3554.
[] [PMID: 30451297]
Fernandez-Rodriguez, S.; Edwards, D.H.; Newton, B.; Griffith, T.M. Attenuated store-operated Ca2+ entry underpins the dual inhibition of nitric oxide and EDHF-type relaxations by iodinated contrast media. Cardiovasc. Res., 2009, 84(3), 470-478.
[] [PMID: 19592569]
Yeon, S.I.; Kim, J.Y.; Yeon, D.S.; Abramowitz, J.; Birnbaumer, L.; Muallem, S.; Lee, Y.H. Transient receptor potential canonical type 3 channels control the vascular contractility of mouse mesenteric arteries. PLoS One, 2014, 9(10), e110413
[] [PMID: 25310225]
Zhang, D.X.; Mendoza, S.A.; Bubolz, A.H.; Mizuno, A.; Ge, Z.D.; Li, R.; Warltier, D.C.; Suzuki, M.; Gutterman, D.D. Transient receptor potential vanilloid type 4-deficient mice exhibit impaired endothelium-dependent relaxation induced by acetylcholine in vitro and in vivo. Hypertension, 2009, 53(3), 532-538.
[] [PMID: 19188524]
Zhao, Y.; Vanhoutte, P.M.; Leung, S.W. Vascular nitric oxide: Beyond eNOS. J. Pharmacol. Sci., 2015, 129(2), 83-94.
[] [PMID: 26499181]
de Wit, C.; Wölfle, S.E. EDHF and gap junctions: important regulators of vascular tone within the microcirculation. Curr. Pharm. Biotechnol., 2007, 8(1), 11-25.
[] [PMID: 17311549]
Shu, X.; Keller, T.C., IV; Begandt, D.; Butcher, J.T.; Biwer, L.; Keller, A.S.; Columbus, L.; Isakson, B.E. Endothelial nitric oxide synthase in the microcirculation. Cell. Mol. Life Sci., 2015, 72(23), 4561-4575.
[] [PMID: 26390975]
Segal, S.S. Integration and modulation of intercellular signaling underlying blood flow control. J. Vasc. Res., 2015, 52(2), 136-157.
[] [PMID: 26368324]
Ledoux, J.; Taylor, M.S.; Bonev, A.D.; Hannah, R.M.; Solodushko, V.; Shui, B.; Tallini, Y.; Kotlikoff, M.I.; Nelson, M.T. Functional architecture of inositol 1,4,5-trisphosphate signaling in restricted spaces of myoendothelial projections. Proc. Natl. Acad. Sci. USA, 2008, 105(28), 9627-9632.
[] [PMID: 18621682]
Dora, K.A.; Gallagher, N.T.; McNeish, A.; Garland, C.J. Modulation of endothelial cell KCa3.1 channels during endothelium-derived hyperpolarizing factor signaling in mesenteric resistance arteries. Circ. Res., 2008, 102(10), 1247-1255.
[] [PMID: 18403729]
Sonkusare, S.K.; Bonev, A.D.; Ledoux, J.; Liedtke, W.; Kotlikoff, M.I.; Heppner, T.J.; Hill-Eubanks, D.C.; Nelson, M.T. Elementary Ca2+ signals through endothelial TRPV4 channels regulate vascular function. Science, 2012, 336(6081), 597-601.
[] [PMID: 22556255]
Bagher, P.; Beleznai, T.; Kansui, Y.; Mitchell, R.; Garland, C.J.; Dora, K.A. Low intravascular pressure activates endothelial cell TRPV4 channels, local Ca2+ events, and IKCa channels, reducing arteriolar tone. Proc. Natl. Acad. Sci. USA, 2012, 109(44), 18174-18179.
[] [PMID: 23071308]
Earley, S.; Gonzales, A.L.; Crnich, R. Endothelium-dependent cerebral artery dilation mediated by TRPA1 and Ca2+-Activated K+ channels. Circ. Res., 2009, 104(8), 987-994.
[] [PMID: 19299646]
Sullivan, M.N.; Francis, M.; Pitts, N.L.; Taylor, M.S.; Earley, S. Optical recording reveals novel properties of GSK1016790A-induced vanilloid transient receptor potential channel TRPV4 activity in primary human endothelial cells. Mol. Pharmacol., 2012, 82(3), 464-472.
[] [PMID: 22689561]
Sullivan, M.N.; Gonzales, A.L.; Pires, P.W.; Bruhl, A.; Leo, M.D.; Li, W.; Oulidi, A.; Boop, F.A.; Feng, Y.; Jaggar, J.H.; Welsh, D.G.; Earley, S. Localized TRPA1 channel Ca2+ signals stimulated by reactive oxygen species promote cerebral artery dilation. Sci. Signal., 2015, 8(358), ra2.
[] [PMID: 25564678]
Stankevicius, E.; Dalsgaard, T.; Kroigaard, C.; Beck, L.; Boedtkjer, E.; Misfeldt, M.W.; Nielsen, G.; Schjorring, O.; Hughes, A.; Simonsen, U. Opening of small and intermediate calcium-activated potassium channels induces relaxation mainly mediated by nitric-oxide release in large arteries and endothelium-derived hyperpolarizing factor in small arteries from rat. J. Pharmacol. Exp. Ther., 2011, 339(3), 842-850.
[] [PMID: 21880870]
Stankevicius, E.; Lopez-Valverde, V.; Rivera, L.; Hughes, A.D.; Mulvany, M.J.; Simonsen, U. Combination of Ca2+ -activated K+ channel blockers inhibits acetylcholine-evoked nitric oxide release in rat superior mesenteric artery. Br. J. Pharmacol., 2006, 149(5), 560-572.
[] [PMID: 16967048]
Sheng, J.Z.; Ella, S.; Davis, M.J.; Hill, M.A.; Braun, A.P. Openers of SKCa and IKCa channels enhance agonist-evoked endothelial nitric oxide synthesis and arteriolar vasodilation. FASEB J., 2009, 23(4), 1138-1145.
[] [PMID: 19074509]
Nilius, B.; Droogmans, G. Ion channels and their functional role in vascular endothelium. Physiol. Rev., 2001, 81(4), 1415-1459.
[] [PMID: 11581493]
Breier, G.; Chavakis, T.; Hirsch, E. Angiogenesis in metabolic-vascular disease. Thromb. Haemost., 2017, 117(7), 1289-1295.
[] [PMID: 28594427]
Haslam, D.W.; James, W.P. Obesity. Lancet, 2005, 366(9492), 1197-1209.
[] [PMID: 16198769]
Prieto, D.; Contreras, C.; Sánchez, A. Endothelial dysfunction, obesity and insulin resistance. Curr. Vasc. Pharmacol., 2014, 12(3), 412-426.
[] [PMID: 24846231]
Feener, E.P.; King, G.L. Vascular dysfunction in diabetes mellitus. Lancet, 1997, 350(Suppl. 1), SI9-SI13.
[] [PMID: 9250277]
Engin, A. Endothelial dysfunction in obesity. Adv. Exp. Med. Biol., 2017, 960, 345-379.
[] [PMID: 28585207]
Weil, B.R.; Westby, C.M.; Van Guilder, G.P.; Greiner, J.J.; Stauffer, B.L.; DeSouza, C.A. Enhanced endothelin-1 system activity with overweight and obesity. Am. J. Physiol. Heart Circ. Physiol., 2011, 301(3), H689-H695.
[] [PMID: 21666117]
Westby, C.M.; Weil, B.R.; Greiner, J.J.; Stauffer, B.L.; DeSouza, C.A. Endothelin-1 vasoconstriction and the age-related decline in endothelium-dependent vasodilatation in men. Clin. Sci. (Lond.), 2011, 120(11), 485-491.
[] [PMID: 21143196]
Stapleton, P.A.; James, M.E.; Goodwill, A.G.; Frisbee, J.C. Obesity and vascular dysfunction. Pathophysiology, 2008, 15(2), 79-89.
[] [PMID: 18571908]
Steinberg, H.O.; Chaker, H.; Leaming, R.; Johnson, A.; Brechtel, G.; Baron, A.D. Obesity/insulin resistance is associated with endothelial dysfunction. Implications for the syndrome of insulin resistance. J. Clin. Invest., 1996, 97(11), 2601-2610.
[] [PMID: 8647954]
Sciacqua, A.; Candigliota, M.; Ceravolo, R.; Scozzafava, A.; Sinopoli, F.; Corsonello, A.; Sesti, G.; Perticone, F. Weight loss in combination with physical activity improves endothelial dysfunction in human obesity. Diabetes Care, 2003, 26(6), 1673-1678.
[] [PMID: 12766092]
Van Guilder, G.P.; Hoetzer, G.L.; Dengel, D.R.; Stauffer, B.L.; DeSouza, C.A. Impaired endothelium-dependent vasodilation in normotensive and normoglycemic obese adult humans. J. Cardiovasc. Pharmacol., 2006, 47(2), 310-313.
[] [PMID: 16495771]
Van Guilder, G.P.; Stauffer, B.L.; Greiner, J.J.; Desouza, C.A. Impaired endothelium-dependent vasodilation in overweight and obese adult humans is not limited to muscarinic receptor agonists. Am. J. Physiol. Heart Circ. Physiol., 2008, 294(4), H1685-H1692.
[] [PMID: 18281379]
De Filippis, E.; Cusi, K.; Ocampo, G.; Berria, R.; Buck, S.; Consoli, A.; Mandarino, L.J. Exercise-induced improvement in vasodilatory function accompanies increased insulin sensitivity in obesity and type 2 diabetes mellitus. J. Clin. Endocrinol. Metab., 2006, 91(12), 4903-4910.
[] [PMID: 17018657]
Woo, K.S.; Chook, P.; Yu, C.W.; Sung, R.Y.; Qiao, M.; Leung, S.S.; Lam, C.W.; Metreweli, C.; Celermajer, D.S. Effects of diet and exercise on obesity-related vascular dysfunction in children. Circulation, 2004, 109(16), 1981-1986.
[] [PMID: 15066949]
Kurtz, T.W.; Morris, R.C.; Pershadsingh, H.A. The Zucker fatty rat as a genetic model of obesity and hypertension. Hypertension, 1989, 13(6 Pt 2), 896-901.
[] [PMID: 2786848]
Schach, C.; Resch, M.; Schmid, P.M.; Riegger, G.A.; Endemann, D.H. Type 2 diabetes: increased expression and contribution of IKCa channels to vasodilation in small mesenteric arteries of ZDF rats. Am. J. Physiol. Heart Circ. Physiol., 2014, 307(8), H1093-H1102.
[] [PMID: 25128173]
Yin, D.D.; Wang, Q.C.; Zhou, X.; Li, Y. Endothelial dysfunction in renal arcuate arteries of obese Zucker rats: The roles of nitric oxide, endothelium-derived hyperpolarizing factors, and calcium-activated K+ channels. PLoS One, 2017, 12(8), e0183124
[] [PMID: 28817716]
Climent, B.; Moreno, L.; Martínez, P.; Contreras, C.; Sánchez, A.; Pérez-Vizcaíno, F.; García-Sacristán, A.; Rivera, L.; Prieto, D. Upregulation of SK3 and IK1 channels contributes to the enhanced endothelial calcium signaling and the preserved coronary relaxation in obese Zucker rats. PLoS One, 2014, 9(10), e109432
[] [PMID: 25302606]
Santiago, E.; Climent, B.; Muñoz, M.; García-Sacristán, A.; Rivera, L.; Prieto, D. Hydrogen peroxide activates store-operated Ca(2+) entry in coronary arteries. Br. J. Pharmacol., 2015, 172(22), 5318-5332.
[] [PMID: 26478127]
Haddock, R.E.; Grayson, T.H.; Morris, M.J.; Howitt, L.; Chadha, P.S.; Sandow, S.L. Diet-induced obesity impairs endothelium-derived hyperpolarization via altered potassium channel signaling mechanisms. PLoS One, 2011, 6(1), e16423
[] [PMID: 21283658]
Katakam, P.V.; Wappler, E.A.; Katz, P.S.; Rutkai, I.; Institoris, A.; Domoki, F.; Gáspár, T.; Grovenburg, S.M.; Snipes, J.A.; Busija, D.W. Depolarization of mitochondria in endothelial cells promotes cerebral artery vasodilation by activation of nitric oxide synthase. Arterioscler. Thromb. Vasc. Biol., 2013, 33(4), 752-759.
[] [PMID: 23329133]
Frisbee, J.C.; Maier, K.G.; Stepp, D.W. Oxidant stress-induced increase in myogenic activation of skeletal muscle resistance arteries in obese Zucker rats. Am. J. Physiol. Heart Circ. Physiol., 2002, 283(6), H2160-H2168.
[] [PMID: 12388303]
Erdei, N.; Tóth, A.; Pásztor, E.T.; Papp, Z.; Edes, I.; Koller, A.; Bagi, Z. High-fat diet-induced reduction in nitric oxide-dependent arteriolar dilation in rats: role of xanthine oxidase-derived superoxide anion. Am. J. Physiol. Heart Circ. Physiol., 2006, 291(5), H2107-H2115.
[] [PMID: 16798827]
Ellis, A.; Cheng, Z.J.; Li, Y.; Jiang, Y.F.; Yang, J.; Pannirselvam, M.; Ding, H.; Hollenberg, M.D.; Triggle, C.R. Effects of a Western diet versus high glucose on endothelium-dependent relaxation in murine micro- and macro-vasculature. Eur. J. Pharmacol., 2008, 601(1-3), 111-117.
[] [PMID: 18996368]
Chadha, P.S.; Haddock, R.E.; Howitt, L.; Morris, M.J.; Murphy, T.V.; Grayson, T.H.; Sandow, S.L. Obesity up-regulates intermediate conductance calcium-activated potassium channels and myoendothelial gap junctions to maintain endothelial vasodilator function. J. Pharmacol. Exp. Ther., 2010, 335(2), 284-293.
[] [PMID: 20671071]
Howitt, L.; Morris, M.J.; Sandow, S.L.; Murphy, T.V. Effect of diet-induced obesity on BK(Ca) function in contraction and dilation of rat isolated middle cerebral artery. Vascul. Pharmacol., 2014, 61(1), 10-15.
[] [PMID: 24576493]
McSherry, I.N.; Sandow, S.L.; Campbell, W.B.; Falck, J.R.; Hill, M.A.; Dora, K.A. A role for heterocellular coupling and EETs in dilation of rat cremaster arteries. Microcirculation, 2006, 13(2), 119-130.
[] [PMID: 16459325]
Earley, S.; Heppner, T.J.; Nelson, M.T.; Brayden, J.E. TRPV4 forms a novel Ca2+ signaling complex with ryanodine receptors and BKCa channels. Circ. Res., 2005, 97(12), 1270-1279.
[] [PMID: 16269659]
Jebelovszki, E.; Kiraly, C.; Erdei, N.; Feher, A.; Pasztor, E.T.; Rutkai, I.; Forster, T.; Edes, I.; Koller, A.; Bagi, Z. High-fat diet-induced obesity leads to increased NO sensitivity of rat coronary arterioles: role of soluble guanylate cyclase activation. Am. J. Physiol. Heart Circ. Physiol., 2008, 294(6), H2558-H2564.
[] [PMID: 18408126]
Feher, A.; Rutkai, I.; Beleznai, T.; Ungvari, Z.; Csiszar, A.; Edes, I.; Bagi, Z. Caveolin-1 limits the contribution of BK(Ca) channel to EDHF-mediated arteriolar dilation: implications in diet-induced obesity. Cardiovasc. Res., 2010, 87(4), 732-739.
[] [PMID: 20299334]
Alioua, A.; Lu, R.; Kumar, Y.; Eghbali, M.; Kundu, P.; Toro, L.; Stefani, E. Slo1 caveolin-binding motif, a mechanism of caveolin-1-Slo1 interaction regulating Slo1 surface expression. J. Biol. Chem., 2008, 283(8), 4808-4817.
[] [PMID: 18079116]
Wang, X.L.; Ye, D.; Peterson, T.E.; Cao, S.; Shah, V.H.; Katusic, Z.S.; Sieck, G.C.; Lee, H.C. Caveolae targeting and regulation of large conductance Ca(2+)-activated K+ channels in vascular endothelial cells. J. Biol. Chem., 2005, 280(12), 11656-11664.
[] [PMID: 15665381]
Laakso, M.; Edelman, S.V.; Brechtel, G.; Baron, A.D. Decreased effect of insulin to stimulate skeletal muscle blood flow in obese man. A novel mechanism for insulin resistance. J. Clin. Invest., 1990, 85(6), 1844-1852.
[] [PMID: 2189893]
de Jongh, R.T.; Serné, E.H.; IJzerman, R.G.; de Vries, G.; Stehouwer, C.D. Impaired microvascular function in obesity: implications for obesity-associated microangiopathy, hypertension, and insulin resistance. Circulation, 2004, 109(21), 2529-2535.
[] [PMID: 15136505]
Estrada, I.A.; Donthamsetty, R.; Debski, P.; Zhou, M.H.; Zhang, S.L.; Yuan, J.X.; Han, W.; Makino, A. STIM1 restores coronary endothelial function in type 1 diabetic mice. Circ. Res., 2012, 111(9), 1166-1175.
[] [PMID: 22896585]
Sheng, J.Z.; Wang, D.; Braun, A.P. DAF-FM (4-amino-5-methylamino-2′,7′-difluorofluorescein) diacetate detects impairment of agonist-stimulated nitric oxide synthesis by elevated glucose in human vascular endothelial cells: reversal by vitamin C and L-sepiapterin. J. Pharmacol. Exp. Ther., 2005, 315(2), 931-940.
[] [PMID: 16093274]
Grayson, T.H.; Chadha, P.S.; Bertrand, P.P.; Chen, H.; Morris, M.J.; Senadheera, S.; Murphy, T.V.; Sandow, S.L. Increased caveolae density and caveolin-1 expression accompany impaired NO-mediated vasorelaxation in diet-induced obesity. Histochem. Cell Biol., 2013, 139(2), 309-321.
[] [PMID: 23007290]
Isshiki, M.; Anderson, R.G. Function of caveolae in Ca2+ entry and Ca2+-dependent signal transduction. Traffic, 2003, 4(11), 717-723.
[] [PMID: 14617355]
Xu, Y.; Buikema, H.; van Gilst, W.H.; Henning, R.H. Caveolae and endothelial dysfunction: filling the caves in cardiovascular disease. Eur. J. Pharmacol., 2008, 585(2-3), 256-260.
[] [PMID: 18423600]
Isshiki, M.; Anderson, R.G. Calcium signal transduction from caveolae. Cell Calcium, 1999, 26(5), 201-208.
[] [PMID: 10643558]
Isshiki, M.; Ando, J.; Yamamoto, K.; Fujita, T.; Ying, Y.; Anderson, R.G. Sites of Ca(2+) wave initiation move with caveolae to the trailing edge of migrating cells. J. Cell Sci., 2002, 115(Pt 3), 475-484.
[PMID: 11861755]
Isshiki, M.; Ying, Y.S.; Fujita, T.; Anderson, R.G. A molecular sensor detects signal transduction from caveolae in living cells. J. Biol. Chem., 2002, 277(45), 43389-43398.
[] [PMID: 12177060]
Brazer, S.C.; Singh, B.B.; Liu, X.; Swaim, W.; Ambudkar, I.S. Caveolin-1 contributes to assembly of store-operated Ca2+ influx channels by regulating plasma membrane localization of TRPC1. J. Biol. Chem., 2003, 278(29), 27208-27215.
[] [PMID: 12732636]
Murata, T.; Lin, M.I.; Huang, Y.; Yu, J.; Bauer, P.M.; Giordano, F.J.; Sessa, W.C. Reexpression of caveolin-1 in endothelium rescues the vascular, cardiac, and pulmonary defects in global caveolin-1 knockout mice. J. Exp. Med., 2007, 204(10), 2373-2382.
[] [PMID: 17893196]
Murata, T.; Lin, M.I.; Stan, R.V.; Bauer, P.M.; Yu, J.; Sessa, W.C. Genetic evidence supporting caveolae microdomain regulation of calcium entry in endothelial cells. J. Biol. Chem., 2007, 282(22), 16631-16643.
[] [PMID: 17416589]
Bohórquez-Hernández, A.; Gratton, E.; Pacheco, J.; Asanov, A.; Vaca, L. Cholesterol modulates the cellular localization of Orai1 channels and its disposition among membrane domains. Biochim. Biophys. Acta Mol. Cell Biol. Lipids, 2017, 1862(12), 1481-1490.
[] [PMID: 28919480]
Darblade, B.; Caillaud, D.; Poirot, M.; Fouque, M.; Thiers, J.C.; Rami, J.; Bayard, F.; Arnal, J.F. Alteration of plasmalemmal caveolae mimics endothelial dysfunction observed in atheromatous rabbit aorta. Cardiovasc. Res., 2001, 50(3), 566-576.
[] [PMID: 11376632]
Bréchard, S.; Tschirhart, E.J. Regulation of superoxide production in neutrophils: role of calcium influx. J. Leukoc. Biol., 2008, 84(5), 1223-1237.
[] [PMID: 18519744]
Wang, Y.W.; Zhang, J.H.; Yu, Y.; Yu, J.; Huang, L. Inhibition of store-operated calcium entry protects endothelial progenitor cells from H2O2-Induced apoptosis. Biomol. Ther. (Seoul), 2016, 24(4), 371-379.
[] [PMID: 27169819]
Berra Romani, R.; Mani-Zaca, B.; Vargaz-Guadarrama, V.A.; Moccia, F.; Tanzi, F.; Trujillo-Hernandez, A. Obesity impairs vascular reactivity and Ca2+ homeostasis in in situ endothelial cells from rat aorta. Acta Physiol. (Oxf.), 2017, 221, 128.
Biwer, L.A.; Taddeo, E.P.; Kenwood, B.M.; Hoehn, K.L.; Straub, A.C.; Isakson, B.E. Two functionally distinct pools of eNOS in endothelium are facilitated by myoendothelial junction lipid composition. Biochim. Biophys. Acta, 2016, 1861(7), 671-679.
[] [PMID: 27106139]
Janoschek, R.; Bae-Gartz, I.; Vohlen, C.; Alcázar, M.A.; Dinger, K.; Appel, S.; Dötsch, J.; Hucklenbruch-Rother, E. Dietary intervention in obese dams protects male offspring from WAT induction of TRPV4, adiposity, and hyperinsulinemia. Obesity (Silver Spring), 2016, 24(6), 1266-1273.
[] [PMID: 27106804]
Sun, W.; Li, C.; Zhang, Y.; Jiang, C.; Zhai, M.; Zhou, Q.; Xiao, L.; Deng, Q. Gene expression changes of thermo-sensitive transient receptor potential channels in obese mice. Cell Biol. Int., 2017, 41(8), 908-913.
[] [PMID: 28464448]
Ma, X.; Du, J.; Zhang, P.; Deng, J.; Liu, J.; Lam, F.F.; Li, R.A.; Huang, Y.; Jin, J.; Yao, X. Functional role of TRPV4-KCa2.3 signaling in vascular endothelial cells in normal and streptozotocin-induced diabetic rats. Hypertension, 2013, 62(1), 134-139.
[] [PMID: 23648706]
Monaghan, K.; McNaughten, J.; McGahon, M.K.; Kelly, C.; Kyle, D.; Yong, P.H.; McGeown, J.G.; Curtis, T.M. Hyperglycemia and diabetes downregulate the functional expression of TRPV4 channels in retinal microvascular endothelium. PLoS One, 2015, 10(6), e0128359
[] [PMID: 26047504]
Mathew John, C.; Khaddaj Mallat, R.; George, G.; Kim, T.; Mishra, R.C.; Braun, A.P. Pharmacologic targeting of endothelial Ca2+-activated K+ channels: A strategy to improve cardiovascular function. Channels (Austin), 2018, 12(1), 126-136.
[] [PMID: 29577810]
Khaddaj-Mallat, R.; Mathew John, C.; Braun, A.P. SKA-31, an activator of endothelial Ca2+-activated K+ channels evokes robust vasodilation in rat mesenteric arteries. Eur. J. Pharmacol., 2018, 831, 60-67.
[] [PMID: 29753043]
Goto, K.; Ohtsubo, T.; Kitazono, T. Endothelium-dependent hyperpolarization (EDH) in hypertension: the role of endothelial ion channels. Int. J. Mol. Sci., 2018, 19(1), E315
[] [PMID: 29361737]
Albarwani, S.; Al-Siyabi, S.; Al-Husseini, I.; Al-Ismail, A.; Al-Lawati, I.; Al-Bahrani, I.; Tanira, M.O. Lisinopril alters contribution of nitric oxide and K(Ca) channels to vasodilatation in small mesenteric arteries of spontaneously hypertensive rats. Physiol. Res., 2015, 64(1), 39-49.
[PMID: 25194131]
Moccia, F.; Ruffinatti, F.A.; Zuccolo, E. Intracellular Ca2+ signals to reconstruct a broken heart: still a theoretical approach? Curr. Drug Targets, 2015, 16(8), 793-815.
[] [PMID: 25523899]
Moccia, F.; Dragoni, S.; Cinelli, M.; Montagnani, S.; Amato, B.; Rosti, V.; Guerra, G.; Tanzi, F. How to utilize Ca2+ signals to rejuvenate the repairative phenotype of senescent endothelial progenitor cells in elderly patients affected by cardiovascular diseases: a useful therapeutic support of surgical approach? BMC Surg., 2013, 13(Suppl. 2), S46.
[] [PMID: 24267290]
Moccia, F.; Poletto, V. May the remodeling of the Ca2+ toolkit in endothelial progenitor cells derived from cancer patients suggest alternative targets for anti-angiogenic treatment? Biochim. Biophys. Acta, 2015, 1853(9), 1958-1973.
[] [PMID: 25447551]
Moccia, F. Remodelling of the Ca2+ toolkit in tumor endothelium as a crucial responsible for the resistance to anticancer therapies. Curr. Signal Transd, 2017, 12(1), 3-18.
Prakriya, M.; Lewis, R.S. Store-operated calcium channels. Physiol. Rev., 2015, 95(4), 1383-1436.
[] [PMID: 26400989]
Moccia, F.; Zuccolo, E.; Poletto, V.; Turin, I.; Guerra, G.; Pedrazzoli, P.; Rosti, V.; Porta, C.; Montagna, D. Targeting stim and orai proteins as an alternative approach in anticancer therapy. Curr. Med. Chem., 2016, 23(30), 3450-3480.
[] [PMID: 27281129]
Moccia, F.; Dragoni, S.; Poletto, V.; Rosti, V.; Tanzi, F.; Ganini, C.; Porta, C. Orai1 and transient receptor potential channels as novel molecular targets to impair tumor neovascularization in renal cell carcinoma and other malignancies. Anticancer. Agents Med. Chem., 2014, 14(2), 296-312.
[] [PMID: 23869775]
Dragoni, S.; Reforgiato, M.; Zuccolo, E.; Poletto, V.; Lodola, F.; Ruffinatti, F.A.; Bonetti, E.; Guerra, G.; Barosi, G.; Rosti, V.; Moccia, F. Dysregulation of VEGF-induced proangiogenic Ca2+ oscillations in primary myelofibrosis-derived endothelial colony-forming cells. Exp. Hematol., 2015, 43(12), 1019-1030.e3.
[] [PMID: 26432919]
Beech, D.J.; Xu, S.Z.; McHugh, D.; Flemming, R. TRPC1 store-operated cationic channel subunit. Cell Calcium, 2003, 33(5-6), 433-440.
[] [PMID: 12765688]
Rubaiy, H.N.; Ludlow, M.J.; Bon, R.S.; Beech, D.J. Pico145 - powerful new tool for TRPC1/4/5 channels. Channels (Austin), 2017, 11(5), 362-364.
[] [PMID: 28399685]
Moccia, F.; Zuccolo, E.; Soda, T.; Tanzi, F.; Guerra, G.; Mapelli, L.; Lodola, F.; D’Angelo, E. Stim and Orai proteins in neuronal Ca(2+) signaling and excitability. Front. Cell. Neurosci., 2015, 9, 153.
[] [PMID: 25964739]
Rahman, S.; Rahman, T. Unveiling some FDA-approved drugs as inhibitors of the store-operated Ca2+ entry pathway. Sci. Rep., 2017, 7(1), 12881.
[] [PMID: 29038464]
Ching, L.C.; Kou, Y.R.; Shyue, S.K.; Su, K.H.; Wei, J.; Cheng, L.C.; Yu, Y.B.; Pan, C.C.; Lee, T.S. Molecular mechanisms of activation of endothelial nitric oxide synthase mediated by transient receptor potential vanilloid type 1. Cardiovasc. Res., 2011, 91(3), 492-501.
[] [PMID: 21493704]
Bratz, I.N.; Dick, G.M.; Tune, J.D.; Edwards, J.M.; Neeb, Z.P.; Dincer, U.D.; Sturek, M. Impaired capsaicin-induced relaxation of coronary arteries in a porcine model of the metabolic syndrome. Am. J. Physiol. Heart Circ. Physiol., 2008, 294(6), H2489-H2496.
[] [PMID: 18390821]
Guarini, G.; Ohanyan, V.A.; Kmetz, J.G.; DelloStritto, D.J.; Thoppil, R.J.; Thodeti, C.K.; Meszaros, J.G.; Damron, D.S.; Bratz, I.N. Disruption of TRPV1-mediated coupling of coronary blood flow to cardiac metabolism in diabetic mice: role of nitric oxide and BK channels. Am. J. Physiol. Heart Circ. Physiol., 2012, 303(2), H216-H223.
[] [PMID: 22610171]
Sun, J.; Pu, Y.; Wang, P.; Chen, S.; Zhao, Y.; Liu, C.; Shang, Q.; Zhu, Z.; Liu, D. TRPV1-mediated UCP2 upregulation ameliorates hyperglycemia-induced endothelial dysfunction. Cardiovasc. Diabetol., 2013, 12, 69.
[] [PMID: 23607427]
Blanc, J.; Alves-Guerra, M.C.; Esposito, B.; Rousset, S.; Gourdy, P.; Ricquier, D.; Tedgui, A.; Miroux, B.; Mallat, Z. Protective role of uncoupling protein 2 in atherosclerosis. Circulation, 2003, 107(3), 388-390.
[] [PMID: 12551860]
McCarty, M.F.; DiNicolantonio, J.J.; O’Keefe, J.H. Capsaicin may have important potential for promoting vascular and metabolic health. Open Heart, 2015, 2(1), e000262
[] [PMID: 26113985]
Xiong, S.; Wang, P.; Ma, L.; Gao, P.; Gong, L.; Li, L.; Li, Q.; Sun, F.; Zhou, X.; He, H.; Chen, J.; Yan, Z.; Liu, D.; Zhu, Z. Ameliorating endothelial mitochondrial dysfunction restores coronary function via transient receptor potential vanilloid 1-mediated protein kinase a/uncoupling protein 2 pathway. Hypertension, 2016, 67(2), 451-460.
[] [PMID: 26667415]
He, D.; Pan, Q.; Chen, Z.; Sun, C.; Zhang, P.; Mao, A.; Zhu, Y.; Li, H.; Lu, C.; Xie, M.; Zhou, Y.; Shen, D.; Tang, C.; Yang, Z.; Jin, J.; Yao, X.; Nilius, B.; Ma, X. Treatment of hypertension by increasing impaired endothelial TRPV4-KCa2.3 interaction. EMBO Mol. Med., 2017, 9(11), 1491-1503.
[] [PMID: 28899928]
Mendoza, S.A.; Fang, J.; Gutterman, D.D.; Wilcox, D.A.; Bubolz, A.H.; Li, R.; Suzuki, M.; Zhang, D.X. TRPV4-mediated endothelial Ca2+ influx and vasodilation in response to shear stress. Am. J. Physiol. Heart Circ. Physiol., 2010, 298(2), H466-H476.
[] [PMID: 19966050]
Ma, X.; He, D.; Ru, X.; Chen, Y.; Cai, Y.; Bruce, I.C.; Xia, Q.; Yao, X.; Jin, J. Apigenin, a plant-derived flavone, activates transient receptor potential vanilloid 4 cation channel. Br. J. Pharmacol., 2012, 166(1), 349-358.
[] [PMID: 22049911]
Peixoto-Neves, D.; Wang, Q.; Leal-Cardoso, J.H.; Rossoni, L.V.; Jaggar, J.H. Eugenol dilates mesenteric arteries and reduces systemic BP by activating endothelial cell TRPV4 channels. Br. J. Pharmacol., 2015, 172(14), 3484-3494.
[] [PMID: 25832173]
White, J.P.; Cibelli, M.; Urban, L.; Nilius, B.; McGeown, J.G.; Nagy, I. TRPV4: molecular conductor of a diverse orchestra. Physiol. Rev., 2016, 96(3), 911-973.
[] [PMID: 27252279]
Pires, P.W.; Sullivan, M.N.; Pritchard, H.A.; Robinson, J.J.; Earley, S. Unitary TRPV3 channel Ca2+ influx events elicit endothelium-dependent dilation of cerebral parenchymal arterioles. Am. J. Physiol. Heart Circ. Physiol., 2015, 309(12), H2031-H2041.
[] [PMID: 26453324]
Senadheera, S.; Kim, Y.; Grayson, T.H.; Toemoe, S.; Kochukov, M.Y.; Abramowitz, J.; Housley, G.D.; Bertrand, R.L.; Chadha, P.S.; Bertrand, P.P.; Murphy, T.V.; Tare, M.; Birnbaumer, L.; Marrelli, S.P.; Sandow, S.L. Transient receptor potential canonical type 3 channels facilitate endothelium-derived hyperpolarization-mediated resistance artery vasodilator activity. Cardiovasc. Res., 2012, 95(4), 439-447.
[] [PMID: 22721989]
Lillo, M.A.; Gaete, P.S.; Puebla, M.; Ardiles, N.M.; Poblete, I.; Becerra, A.; Simon, F.; Figueroa, X.F. Critical contribution of Na(+)-Ca(2+) exchanger to the Ca(2+)-mediated vasodilation activated in endothelial cells of resistance arteries. FASEB J., 2018, 32(4), 2137-2147.
[] [PMID: 29217667]

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy