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Microvascular Research biology and pathology - part 7

Tăng cholesterol máu là một yếu tố nguy cơ được thành lập cho sự phát triển của bệnh tim mạch. Các tổn thương xơ vữa động mạch là kết quả từ một độ cao duy trì nồng độ cholesterol trong máu có liên quan đến sự tích tụ của các tế bào viêm và tiểu cầu tạo điều kiện thuận lợi cho việc tích tụ các chất béo | Chapter 103 Microvascular Responses to Hypercholesterolemia Karen Y. Stokes and D. Neil Granger Louisiana Stale University Health Sciences Center Shreveport Louisiana Introduction Hypercholesterolemia is an established risk factor for the development of cardiovascular diseases. The atherosclerotic lesions that result from a sustained elevation in blood cholesterol concentration are associated with an accumulation of inflammatory cells and platelets that facilitate the deposition of lipids in the walls of lesion-prone arteries. However long before these changes occur in large arteries inflammatory and prothrombogenic responses are observed in arterioles and venules throughout the vascular system Figure 1 . These responses are manifested as endothelial dysfunction and the binding of leukocytes and platelets to the vessel wall. Although several mechanisms have been proposed to explain the phenotypic changes that occur in the microvasculature during hypercholesterolemia oxidative stress and a diminished bioavailability of nitric oxide NO have gained much attention in recent years. This chapter describes the responses of the microcirculation to hypercholesterolemia and addresses the mechanism that underlies this systemic inflammatory condition. Hypercholesterolemia and Arterioles Under normal physiological conditions basal NO production by endothelial cells maintains vascular tone and inhibits inflammation. However during hypercholesterolemia several events occur that negatively influence the vasodilatory role of NO in arterioles. Although the concentration of L-arginine the substrate for NO synthase NOS is not reduced during hypercholesterolemia the interaction between L-arginine and endothelial NOS may be blocked by the endogenous inhibitor asymmetric dimethylarginine ADMA the levels of which are increased during hypercholesterolemia. The elevated ADMA levels likely result from the diminished activity of dimethylarginine dimethylaminohydrolase DDAH which normally .