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Current Medicinal Chemistry


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

Review Article

The Role of the Endothelium in Premature Atherosclerosis: Molecular Mechanisms

Author(s): Michael Spartalis*, Eleftherios Spartalis, Antonios Athanasiou, ">Stavroula A. Paschou, ">Christos Kontogiannis, ">Georgios Georgiopoulos, Dimitrios C. Iliopoulos and Vassilis Voudris

Volume 27 , Issue 7 , 2020

Page: [1041 - 1051] Pages: 11

DOI: 10.2174/0929867326666190911141951

Price: $65


Atherosclerotic disease is still one of the leading causes of mortality. Atherosclerosis is a complex progressive and systematic artery disease that involves the intima of the large and middle artery vessels. The inflammation has a key role in the pathophysiological process of the disease and the infiltration of the intima from monocytes, macrophages and T-lymphocytes combined with endothelial dysfunction and accumulated oxidized low-density lipoprotein (LDL) are the main findings of atherogenesis. The development of atherosclerosis involves multiple genetic and environmental factors. Although a large number of genes, genetic polymorphisms, and susceptible loci have been identified in chromosomal regions associated with atherosclerosis, it is the epigenetic process that regulates the chromosomal organization and genetic expression that plays a critical role in the pathogenesis of atherosclerosis. Despite the positive progress made in understanding the pathogenesis of atherosclerosis, the knowledge about the disease remains scarce.

Keywords: Endothelium, endothelial dysfunction, molecular, cardiovascular disease, atherosclerosis, systematic artery disease.

Ross, R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature, 1993, 362(6423), 801-809.
[] [PMID: 8479518]
Kodama, T.; Freeman, M.; Rohrer, L.; Zabrecky, J.; Matsudaira, P.; Krieger, M. Type I macrophage scavenger receptor contains alpha-helical and collagen-like coiled coils. Nature, 1990, 343(6258), 531-535.
[] [PMID: 2300204]
Rohrer, L.; Freeman, M.; Kodama, T.; Penman, M.; Krieger, M. Coiled-coil fibrous domains mediate ligand binding by macrophage scavenger receptor type II. Nature, 1990, 343(6258), 570-572.
[] [PMID: 2300208]
Gough, P.J.; Greaves, D.R.; Gordon, S. A naturally occurring isoform of the human macrophage scavenger receptor (SR-A) gene generated by alternative splicing blocks modified LDL uptake. J. Lipid Res., 1998, 39(3), 531-543.
[PMID: 9548586]
Ylä-Herttuala, S.; Rosenfeld, M.E.; Parthasarathy, S.; Sigal, E.; Särkioja, T.; Witztum, J.L.; Steinberg, D. Gene expression in macrophage-rich human atherosclerotic lesions. 15-lipoxygenase and acetyl low density lipoprotein receptor messenger RNA colocalize with oxidation specific lipid-protein adducts. J. Clin. Invest., 1991, 87(4), 1146-1152.
[] [PMID: 2010531]
Greaves, D.R.; Gough, P.J.; Gordon, S. Recent progress in defining the role of scavenger receptors in lipid transport, atherosclerosis and host defence. Curr. Opin. Lipidol., 1998, 9(5), 425-432.
[] [PMID: 9812196]
Hiltunen, T.P.; Luoma, J.S.; Nikkari, T.; Ylä-Herttuala, S. Expression of LDL receptor, VLDL receptor, LDL receptor-related protein, and scavenger receptor in rabbit atherosclerotic lesions: marked induction of scavenger receptor and VLDL receptor expression during lesion development. Circulation, 1998, 97(11), 1079-1086.
[] [PMID: 9531255]
Naito, M.; Suzuki, H.; Mori, T.; Matsumoto, A.; Kodama, T.; Takahashi, K. Coexpression of type I and type II human macrophage scavenger receptors in macrophages of various organs and foam cells in atherosclerotic lesions. Am. J. Pathol., 1992, 141(3), 591-599.
[PMID: 1519666]
Suzuki, H.; Kurihara, Y.; Takeya, M.; Kamada, N.; Kataoka, M.; Jishage, K.; Ueda, O.; Sakaguchi, H.; Higashi, T.; Suzuki, T.; Takashima, Y.; Kawabe, Y.; Cynshi, O.; Wada, Y.; Honda, M.; Kurihara, H.; Aburatani, H.; Doi, T.; Matsumoto, A.; Azuma, S.; Noda, T.; Toyoda, Y.; Itakura, H.; Yazaki, Y.; Kodama, T. A role for macrophage scavenger receptors in atherosclerosis and susceptibility to infection. Nature, 1997, 386(6622), 292-296.
[] [PMID: 9069289]
Vlassara, H.; Brownlee, M.; Cerami, A. High-affinity-receptor-mediated uptake and degradation of glucose-modified proteins: a potential mechanism for the removal of senescent macromolecules. Proc. Natl. Acad. Sci. USA, 1985, 82(17), 5588-5592.
[] [PMID: 2994035]
Takata, K.; Horiuchi, S.; Araki, N.; Shiga, M.; Saitoh, M.; Morino, Y. Endocytic uptake of nonenzymatically glycosylated proteins is mediated by a scavenger receptor for aldehyde-modified proteins. J. Biol. Chem., 1988, 263(29), 14819-14825.
[PMID: 2844787]
el Khoury, J.; Thomas, C.A.; Loike, J.D.; Hickman, S.E.; Cao, L.; Silverstein, S.C. Macrophages adhere to glucose-modified basement membrane collagen IV via their scavenger receptors. J. Biol. Chem., 1994, 269(14), 10197-10200.
[PMID: 8144597]
Fraser, I.; Hughes, D.; Gordon, S. Divalent cation-independent macrophage adhesion inhibited by monoclonal antibody to murine scavenger receptor. Nature, 1993, 364(6435), 343-346.
[] [PMID: 8332192]
Platt, N.; da Silva, R.P.; Gordon, S. Class A scavenger receptors and the phagocytosis of apoptotic cells. Immunol. Lett., 1999, 65(1-2), 15-19.
[] [PMID: 10065621]
Terpstra, V.; Kondratenko, N.; Steinberg, D. Macrophages lacking scavenger receptor A show a decrease in binding and uptake of acetylated low-density lipoprotein and of apoptotic thymocytes, but not of oxidatively damaged red blood cells. Proc. Natl. Acad. Sci. USA, 1997, 94(15), 8127-8131.
[] [PMID: 9223326]
Yokota, T.; Ehlin-Henriksson, B.; Hansson, G.K. Scavenger receptors mediate adhesion of activated B lymphocytes. Exp. Cell Res., 1998, 239(1), 16-22.
[] [PMID: 9511720]
Dunne, D.W.; Resnick, D.; Greenberg, J.; Krieger, M.; Joiner, K.A. The type I macrophage scavenger receptor binds to gram-positive bacteria and recognizes lipoteichoic acid. Proc. Natl. Acad. Sci. USA, 1994, 91(5), 1863-1867.
[] [PMID: 8127896]
Hampton, R.Y.; Golenbock, D.T.; Penman, M.; Krieger, M.; Raetz, C.R. Recognition and plasma clearance of endotoxin by scavenger receptors. Nature, 1991, 352(6333), 342-344.
[] [PMID: 1852209]
Haworth, R.; Platt, N.; Keshav, S.; Hughes, D.; Darley, E.; Suzuki, H.; Kurihara, Y.; Kodama, T.; Gordon, S. The macrophage scavenger receptor type A is expressed by activated macrophages and protects the host against lethal endotoxic shock. J. Exp. Med., 1997, 186(9), 1431-1439.
[] [PMID: 9348300]
Lougheed, M.; Lum, C.M.; Ling, W.; Suzuki, H.; Kodama, T.; Steinbrecher, U. High affinity saturable uptake of oxidized low density lipoprotein by macrophages from mice lacking the scavenger receptor class A type I/II. J. Biol. Chem., 1997, 272(20), 12938-12944.
[] [PMID: 9148899]
Nicholson, A.C. Expression of CD36 in macrophages and atherosclerosis: the role of lipid regulation of PPARgamma signaling. Trends Cardiovasc. Med., 2004, 14(1), 8-12.
[] [PMID: 14720468]
Auer, J.; Weber, T.; Berent, R.; Lassnig, E.; Lamm, G.; Eber, B. Genetic polymorphisms in cytokine and adhesion molecule genes in coronary artery disease. Am. J. Pharmacogenomics, 2003, 3(5), 317-328.
[] [PMID: 14575520]
Ito, T.; Ikeda, U. Inflammatory cytokines and cardiovascular disease. Curr. Drug Targets Inflamm. Allergy, 2003, 2(3), 257-265.
[] [PMID: 14561160]
Makris, S.; Venetsanou, K.; Spartalis, E.; Kontogiannis, C.; Georgiopoulos, G.; Spartalis, M.; Tsilimigras, D.I.; Moris, D.; Kakisis, I.; Karaolanis, G.; Patelis, N.; Zymvragoudakis, V.; Papasilekas, T.I.; Themistoklis, K.M.; Lazaris, A. Changes in serum leptin levels as well as sICAM-1 and sVCAM-1 soluble adhesion molecules during carotid endarterectomy. Eur. Rev. Med. Pharmacol. Sci., 2019, 23(5), 2257-2262.
[PMID: 30915774]
Novelli, G.; Borgiani, P.; Giardina, E.; Mango, R.; Contino, G.; Romeo, F.; Mehta, J.L. Role of genetics in prevention of coronary atherosclerosis. Curr. Opin. Cardiol., 2003, 18(5), 368-371.
[] [PMID: 12960469]
Rasmussen, H.S.; Rasmussen, C.S.; Macko, J. VEGF gene therapy for coronary artery disease and peripheral vascular disease. Cardiovasc. Radiat. Med., 2002, 3(2), 114-117.
[] [PMID: 12699842]
Humphries, S.E.; Morgan, L. Genetic risk factors for stroke and carotid atherosclerosis: insights into pathophysiology from candidate gene approaches. Lancet Neurol., 2004, 3(4), 227-235.
[] [PMID: 15039035 ]
Hamilton, C.A.; Miller, W.H.; Al-Benna, S.; Brosnan, M.J.; Drummond, R.D.; McBride, M.W.; Dominiczak, A.F. Strategies to reduce oxidative stress in cardiovascular disease. Clin. Sci. (Lond.), 2004, 106(3), 219-234.
[] [PMID: 14733610]
Moris, D.; Spartalis, M.; Tzatzaki, E.; Spartalis, E.; Karachaliou, G.S.; Triantafyllis, A.S.; Karaolanis, G.I.; Tsilimigras, D.I.; Theocharis, S. The role of reactive oxygen species in myocardial redox signaling and regulation. Ann. Transl. Med., 2017, 5(16), 324.
[] [PMID: 28861421]
Moris, D.; Spartalis, M.; Spartalis, E.; Karachaliou, G.S.; Karaolanis, G.I.; Tsourouflis, G.; Tsilimigras, D.I.; Tzatzaki, E.; Theocharis, S. The role of reactive oxygen species in the pathophysiology of cardiovascular diseases and the clinical significance of myocardial redox. Ann. Transl. Med., 2017, 5(16), 326.
[] [PMID: 28861423]
Tham, D.M.; Wang, Y.X.; Rutledge, J.C. Modulation of vascular inflammation by PPARs. Drug News Perspect., 2003, 16(2), 109-116.
[] [PMID: 12792672]
Martinet, W.; Kockx, M.M. Apoptosis in atheroclerosis: implications for plaque destabilization. Verh. K. Acad. Geneeskd. Belg., 2004, 66(1), 61-79.
[PMID: 15074082]
Khurana, R.; Simons, M. Insights from angiogenesis trials using fibroblast growth factor for advanced arteriosclerotic disease. Trends Cardiovasc. Med., 2003, 13(3), 116-122.
[] [PMID: 12691676]
Major, C.D.; Santulli, R.J.; Derian, C.K.; Andrade-Gordon, P. Extracellular mediators in atherosclerosis and thrombosis: lessons from thrombin receptor knockout mice. Arterioscler. Thromb. Vasc. Biol., 2003, 23(6), 931-939.
[] [PMID: 12676802]
Janssens, S.P. Applied gene therapy in preclinical models of vascular injury. Curr. Atheroscler. Rep., 2003, 5(3), 186-190.
[] [PMID: 12667430]
Baker, A.H. Development and use of gene transfer for treatment of cardiovascular disease. J. Card. Surg., 2002, 17(6), 543-548.
[] [PMID: 12643466]

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