Coronary microvascular and cardiac dysfunction due to homocysteine pathometabolism; a complex therapeutic design.

Coronary microvascular and cardiac dysfunction due to homocysteine pathometabolism; a complex therapeutic design. Curr Pharm Des. 2018 Jun 25;: Authors: Koller A, Szenasi A, Dornyei G, Kovacs N, Lelbach A, Kovacs I Abstract In various metabolic diseases both the coronary circulation and cardiac metabolism are altered. Here we summarize the effects of a condition called hyperhomocysteinemia (HHcy) - which can develop due to genetic or environmental causes - on the function of coronary microvessels and heart. This metabolic disease is underappreciated, yet even mild or moderate elevation of plasma concentrations of homocystein (Hcy, plasma Hcy >16 M), a sulfur-containing amino acid produced via methionine metabolism) leads to coronary and peripheral artery and even venous vessel diseases, leading to vasomotor dysfunction and increased thrombosis, consequently increased morbidity and mortality. Yet the underlying mechanisms are not yet revealed. Recent studies indicated that there are common pathomechanisms, which may affect all cellular function involved. Two main mechanisms are the dysfunction of nitric oxide (NO) pathway resulting reduced dilator responses of arteries and arterioles with methionine diet-induced hyperhomocysteinemia, and the simultaneously increased thromboxane A2 (TXA2) activity both in vessels and platelets. These changes are likely due to an increased production of reactive oxidative species (oxidative stress...
Source: Current Pharmaceutical Design - Category: Drugs & Pharmacology Authors: Tags: Curr Pharm Des Source Type: research