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Open AccessJournal ArticleDOI

Hyperhomocysteinemia and Endothelial Dysfunction.

Zhongjian Cheng, +2 more
- 01 May 2009 - 
- Vol. 5, Iss: 2, pp 158-165
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TLDR
Six mechanisms have been suggested explaining HHcy-induced endothelial dysfunction and the goal of this review is to elaborate these mechanisms and to discuss biological and molecular events related to HHCy-induced ED.
Abstract
Hyperhomocysteinemia (HHcy) is a significant and independent risk factor for cardiovascular diseases. Endothelial dysfunction (ED) is the earliest indicator of atherosclerosis and vascular diseases. We and others have shown that HHcy induced ED in human and in animal models of HHcy induced by either high-methionine load or genetic deficiency. Six mechanisms have been suggested explaining HHcy-induced ED. These include 1) nitric oxide inhibition, 2) prostanoids regulation, 3) endothelium-derived hyperpolarizing factors suppression, 4) angiotensin II receptor-1 activation, 5) endothelin-1 induction, and 6) oxidative stress. The goal of this review is to elaborate these mechanisms and to discuss biological and molecular events related to HHcy-induced ED.

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Citations
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Homocysteine-Induced Endothelial Dysfunction

TL;DR: This review discussed and in particular emphasis the potential cellular pathways and the biological processes involved that lead to homocysteine-induced endothelial dysfunction, in particular in the impaired endothelial dependent dilatation aspect.
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Circulating biologic markers of endothelial dysfunction in cerebral small vessel disease: A review.

TL;DR: This review examines the main molecular factors involved in both endothelial function and dysfunction, and the evidence linking endothelial dysfunction with cerebral SVD, and gives an overview of clinical studies that have investigated the possible association between endothelial circulating biomarkers and SVD-related brain changes.
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Vascular endothelial dysfunction and pharmacological treatment.

TL;DR: Experimental and clinical studies have demonstrated that a variety of currently used or investigational drugs, such as angiotensin-converting enzyme inhibitors, ang Elliotensin AT1 receptors blockers, angiotENSin-(1-7), antioxidants, beta-blockers, calcium channel blockers, endothelial NO synthase enhancers, phosphodiesterase 5 inhibitors, sphingosine-1-phosphate and statins, exert endothelial protective effects.
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Immunosuppressive/anti-inflammatory cytokines directly and indirectly inhibit endothelial dysfunction--a novel mechanism for maintaining vascular function.

TL;DR: It is suggested that anti-inflammatory/immunosuppressive cytokines serve as novel therapeutic targets for inhibiting endothelial dysfunction, vascular inflammation and cardio- and cerebro-vascular diseases.
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Copper and homocysteine in cardiovascular diseases

TL;DR: A comprehensive understanding of Cu speciation and a development of selective modulation of Cu coordination to Cu-binding molecules to avoid Cu-Hcy complex formation would effectively improve the condition of cardiovascular disease.
References
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Journal ArticleDOI

The pathogenesis of coronary artery disease. A possible role for methionine metabolism.

TL;DR: A reduced ability to metabolise homocysteine in some patients with premature coronary artery disease when this pathway is stressed is suggested.
Journal ArticleDOI

Vascular dysfunction in monkeys with diet-induced hyperhomocyst(e)inemia.

TL;DR: It is concluded that diet-induced moderate hyperhomocyst(e)inemia is associated with altered vascular function and relaxation to acetylcholine and, to a lesser extent, nitroprusside was impaired ex vivo in carotid arteries from monkeys fed modified diet.
Journal ArticleDOI

Folic Acid Improves Endothelial Function in Coronary Artery Disease via Mechanisms Largely Independent of Homocysteine Lowering

TL;DR: Folic acid improves endothelial function in CAD acutely by a mechanism largely independent of homocysteine, according to a randomized, placebo-controlled study undertaken in 33 patients.
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