Atherogenic Lipids, Vascular Dysfunction, and Clinical Signs of Ischemic Heart Disease

作者：Andrew Peter Selwyn, Scott Kinlay, Peter Libby, Peter Ganz · 发表于：Circulation · 年份：1997 · DOI：10.1161/01.cir.95.1.5 · 被引用次数：100 · 研究领域：Lipoproteins and Cardiovascular Health、Cardiovascular Disease and Adiposity、Diabetes, Cardiovascular Risks, and Lipoproteins

LDL is oxidized in vascular endothelial cells to a highly injurious product that results in characteristic cell dysfunction(s) in large arteries and resistance vessels. The characteristic dysfunctions (ie, loss of dilation, constriction, thrombosis, and inflammation) operate before and throughout the development of atherosclerosis and particularly during plaque rupture. Although oxidized LDL appears to induce these cell/vessel wall dysfunctions in a time- and concentration-dependent manner, Tamai and colleagues have shown that this interaction can be dynamic in that a reduction in lipids restores endothelium-dependent vasomotor function almost immediately. The same intervention (ie, lipid lowering) also appears to stabilize atheroma in the long term, improves endothelium-dependent vasomotion over months, and results in a reduction in clinical signs of risk in coronary heart disease (ie, ischemia and the need for revascularization). The above leads us to some important but unanswered questions. Can we rely on clinical measures of arterial vasomotor dysfunction to represent the other important cell dysfunctions (eg, inflammation, abnormal growth) while monitoring the response to therapeutic interventions? How can we effectively inhibit oxidation of LDL in the arterial wall, and is this useful in reversing the many cell dysfunctions and clinical sequelae of coronary atherosclerosis? What is the time course for restoration of endothelial dysfunction in the atherosclerotic epicard...