The relationship between the endothelium and the vessel wall
Cardiovascular Center, Cardiology, University Hospital, Zurich, Switzerland
* Correspondence: Thomas E. Lüscher, MD, Head of Cardiology, Cardiovascular Center, Cardiology, University Hospital, CH-8091 Zurich, Switzerland.
Abstract
The endothelium is located at a strategic position within the vessel wall, being directly exposed to mechanical forces exerted by the blood, and to hormones and noxious substances. The endothelium (an autocrine, paracrine and endocrine organ) is a key player in regulation of vascular tone, thrombogenesis, inflammation and vessel growth. A crucial mediator of proper function of the endothelium is nitric oxide and its bioavailability. Cardiovascular risk factors such as dyslipidaemia, hypertension, diabetes and smoking result in a decreased nitric oxide bioavailability and enhance production of endothelial vasoconstrictors, such as endothelin-1 and oxygen free radicals. Endothelial dysfunction is the key step in atherogenesis and has been shown to predict clinical outcome. Hence, novel treatments that are aimed at improving endothelial function, such as statins and blockers of the renin-angiotensin system, are of particular clinical importance.
Key Words: Endothelial function endothelin endothelium nitric oxide vessel wall
References
- Furchgott RE, Zawadzki JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. 1980;288:373376[CrossRef][Medline]
- Napoli C, D'Armiento FP, Mancini FP, et al. Fatty streak formation occurs in human fetal aortas and is greatly enhanced by maternal hypercholesterolemia. Intimal accumulation of low density lipoprotein and its oxidation precede monocyte recruitment into early atherosclerotic lesions. J Clin Invest. 1997;100:26802690[Web of Science][Medline]
- Stary HC, Chandler AB, Glagov S, et al. A definition of initial, fatty streak, and intermediate lesions of atherosclerosis. A report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association. Circulation. 1994;89:24622478
[Abstract/Free Full Text] - Ross R. Atherosclerosis: an inflammatory disease. N Engl J Med. 1999;340:115126
[Free Full Text] - Tanner FC, Meier P, Greutert H, Champion C, Nabel EG, Lüscher TF. Nitric oxide modulates expression of cell cycle regulatory proteins: a cytostatic strategy for inhibition of human vascular smooth muscle cell proliferation. Circulation. 2000;101:19821989
[Abstract/Free Full Text] - Lüscher TF, Vanhoutte PM. The Endothelium: Modulator of Cardiovascular Function. Boca Ramon: CRC Press; 1990.
- Yanagisawa M, Kurihara H, Kimura S, et al. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature. 1988;332:411415[CrossRef][Medline]
- Zeiher AM, Drexler H, Saurbier B, Just H. Endothelium-mediated coronary blood flow modulation in humans. Effects of age, atherosclerosis, hypercholesterolemia, and hypertension. J Clin Invest. 1993;92:652662
- Johnstone MT, Creager SJ, Scales KM, Cusco JA, Lee BK, Creager MA. Impaired endothelium-dependent vasodilation in patients with insulin-dependent diabetes mellitus. Circulation. 1993;88:25102516
[Abstract/Free Full Text] - Zeiher AM, Schachinger V, Minners J. Long-term cigarette smoking impairs endothelium-dependent coronary arterial vasodilator function. Circulation. 1995;92:10941100
[Abstract/Free Full Text] - Chowienczyk PJ, Watts GF, Cockcroft JR, Ritter JM. Impaired endothelium-dependent vasodilation of forearm resistance vessels in hypercholesterolaemia. Lancet. 1992;340:14301432[CrossRef][Web of Science][Medline]
- Creager MA, Cooke JP, Mendelsohn ME, et al. Impaired vasodilation of forearm resistance vessels in hypercholesterolemic humans. J Clin Invest. 1990;86:228234
- Taddei S, Virdis A, Mattei P, et al. Aging and endothelial function in normotensive subjects and patients with essential hypertension. Circulation. 1995;91:19811987
[Abstract/Free Full Text] - Taddei S, Virdis A, Ghiadoni L, et al. Menopause is associated with endothelial dysfunction in women. Hypertension. 1996;28:576582
[Abstract/Free Full Text] - Linder L, Kiowski W, Buhler FR, Lüscher TF. Indirect evidence for release of endothelium-derived relaxing factor in human forearm circulation in vivo. Blunted response in essential hypertension. Circulation. 1990;81:17621767
[Abstract/Free Full Text] - Taddei S, Virdis A, Mattei P, Salvetti A. Vasodilation to acetylcholine in primary and secondary forms of human hypertension. Hypertension. 1993;21:929933
[Abstract/Free Full Text] - Rubanyi GM, Romero JC, Vanhoutte PM. Flow-induced release of endothelium-derived relaxing factor. Am J Physiol. 1986;250:H1145H1149
- Anderson EA, Mark AL. Flow-mediated and reflex changes in large peripheral artery tone in humans. Circulation. 1989;79:93100
[Abstract/Free Full Text] - Palmer RM, Ferrige AG, Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature. 1987;327:524526[CrossRef][Medline]
- Stamler JS, Singel DJ, Loscalzo J. Biochemistry of nitric oxide and its redox-activated forms. Science. 1992;258:18981902
[Abstract/Free Full Text] - Oemar BS, Tschudi MR, Godoy N, Brovkovich V, Malinski T, Lüscher TE. Reduced endothelial nitric oxide synthase expression and production in human atherosclerosis. Circulation. 1998;97:24942498
[Abstract/Free Full Text] - Suwaidi JA, Hamasaki S, Higano ST, Nishimura RA, Holmes DR Jr, Lerman A. Long-term follow-up of patients with mild coronary artery disease and endothelial dysfunction. Circulation. 2000;101:948954
[Abstract/Free Full Text] - Perticone F, Ceravolo R, Pujia A, et al. Prognostic significance of endothelial dysfunction in hypertensive patients. Circulation. 2001;104:191196
[Abstract/Free Full Text] - Stroes ES, Koomans HA, de Bruin TW, Rabelink TJ. Vascular function in the forearm of hypercholesterolaemic patients off and on lipid-lowering medication. Lancet. 1995;346:467471[CrossRef][Web of Science][Medline]
- O'Driscoll G, Green D, Taylor RR. Simvastatin, an HMG-coenzyme A reductase inhibitor, improves endothelial function within 1 month. Circulation. 1997;95:11261131
[Abstract/Free Full Text] - Stroes E, Kasteleia J, Cosentino F, et al. Tetrahydrobiopterin restores endothelial function in hypercholesterolemia. J Clin Invest. 1997;99:4146[Web of Science][Medline]
- Mancini GB, Henry GC, Macaya C, et al. Angiotensin-converting enzyme inhibition with quinapril improves endothelial vasomotor dysfunction in patients with coronary artery disease. The TREND (Trial on Reversing Endothelial Dysfunction) Study. Circulation. 1996;94:258265
[Abstract/Free Full Text] - Lüscher TF, Boulanger CM, Dohi Y, Yang ZH. Endothelium-derived contracting factors. Hypertension. 1992;19:117130
[Abstract/Free Full Text] - Boulanger C, Lüscher TF. Release of endothelin from the porcine aorta. Inhibition by endothelium-derived nitric oxide. J Clin Invest. 1990;85:587590
- Hu RM, Levin ER, Pedram A, Frank HJ. Atrial natriuretic peptide inhibits the production and secretion of endothelin from cultured endothelial cells. Mediation through the C receptor. J Biol Chem. 1992;267:1738417389
[Abstract/Free Full Text] - Sakurai T, Yanagisawa M, Takuwa Y, et al. Cloning of a cDNA encoding a non-isopeptide-selective subtype of the endothelin receptor. Nature. 1990;348:732735[CrossRef][Medline]
- Arai H, Hori S, Aramori I, Ohkubo H, Nakanishi S. Cloning and expression of a cDNA encoding an endothelin receptor. Nature. 1990;348:730732[CrossRef][Medline]
- Kiowski W, Lüscher TF, Linder L, Buhler FR. Endothelin-1-induced vasoconstriction in humans. Reversal by calcium channel blockade but not by nitrovasodilators or endothelium-derived relaxing factor. Circulation. 1991;83:469475
[Abstract/Free Full Text] - Davenport AP, Kuc RE, Maguire JJ, Harland SP. ETA receptors predominate in the human vasculature and mediate constriction. J Cardiovasc Pharmacol. 1995;26(suppl 3):S265S267
- Verhaar MC, Strachan FE, Newby DE, et al. Endothelin-A receptor antagonist-mediated vasodilatation is attenuated by inhibition of nitric oxide synthesis and by endothelin-B receptor blockade. Circulation. 1998;97:752756
[Abstract/Free Full Text] - Cody RJ, Haas GJ, Binkley PF, Capers Q, Kelley R. Plasma endothelin correlates with the extent of pulmonary hypertension in patients with chronic congestive heart failure. Circulation. 1992;85:504509
[Abstract/Free Full Text] - Wei CM, Lerman A, Rodeheffer RJ, et al. Endothelin in human congestive heart failure. Circulation. 1994;89:15801586
[Abstract/Free Full Text] - Pacher R, Stanek B, Hulsmann M, et al. Prognostic impact of big endothelin-1 plasma concentrations compared with invasive hemodynamic evaluation in severe heart failure. J Am Coll Cardiol. 1996;27:633641[Abstract]
- Teerlink JR, Loffler BM, Hess P, Maire JP, Clozel M, Clozel JP. Role of endothelin in the maintenance of blood pressure in conscious rats with chronic heart failure. Acute effects of the endothelin receptor antagonist Ro 47-0203 (bosentan). Circulation. 1994;90:25102518
[Abstract/Free Full Text] - Pousset F, Isnard R, Lechat P, et al. Prognostic value of plasma endothelin-1 in patients with chronic heart failure. Eur Heart J. 1997;18:254258
[Abstract/Free Full Text] - Hulsmann M, Stanek B, Frey B, et al. Value of cardiopulmonary exercise testing and big endothelin plasma levels to predict short-term prognosis of patients with chronic heart failure. J Am Coll Cardiol. 1998;32:16951700
[Abstract/Free Full Text] - Zolk O, Quattek J, Sitzler G, et al. Expression of endothelin-1, endothelin-converting enzyme, and endothelin receptors in chronic heart failure. Circulation. 1999;99:21182123
[Abstract/Free Full Text] - Spieker LE, Noll G, Ruschitzka FT, Lüscher TF. Endothelin receptor antagonists in congestive heart failure: a new therapeutic principle for the future? J Am Coll Cardiol. 2001;37:14931505
[Abstract/Free Full Text]
This article has been cited by other articles:
![]() |
C.-H. Cheng, T. Kikuchi, Y.-H. Chen, N. G. A.-A.-A. Sabbagha, Y.-C. Lee, H.-J. Pan, C. Chang, and Y.-T. Chen Mutations in the SLC2A10 gene cause arterial abnormalities in mice Cardiovasc Res, February 1, 2009; 81(2): 381 - 388. [Abstract] [Full Text] [PDF] |
||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
