Update on the pathophysiology of aortic stenosis

作者：Rajamannan Nalini M^*

来源：European Heart Journal - Supplements, 2008, 10(E): E4-E10.

DOI：10.1093/eurheartj/sun013

• aortic valve stenosis
• pathophysiology
• atherosclerosis
• calcification
• endothelial dysfunction

The objective of this review is to explain the basis for the current appreciation of the role of active atherosclerotic and bone-forming processes in the pathophysiology of calcific aortic stenosis (AS). Relevant epidemiological, histopathological, and experimental studies are reviewed. Calcific AS and atherosclerosis share similar risk factors, including elevated LDL cholesterol levels, hypertension, mate gender, smoking, and diabetes mellitus. Both atherosclerosis and calcific AS often occur in individuals with familial hypercholesterolaemia, and elderly patients with AS are also at an increased risk of myocardial infarction and death from cardiovascular causes. Lipoprotein deposition is prominent in both conditions. Aortic valve mineralisation occurs as the result of mechanisms similar to those active in bone formation, including upregulation of the Lrp5 pathway and the presence of an osteoblast phenotype in calcified valves. An active atherosclerosis-type pathophysiology involving oxidative stress, inflammation, and endothelial dysfunction in aortic valves has been induced by hypercholesterolaemia, and inhibited by administering HMG-CoA reductase inhibitors (statins), in animal models. Evidence of endothelial dysfunction with neovascularisation and an increase in endothelial macrophages and metalloproteinases has been found in surgically excised human valves with calcific AS. The initiating factors and pathophysiology of calcific AS are broadly similar to those of atherosclerosis of coronary and other arteries. The sclerosis and calcification of aortic valves may therefore be addressed with pharmacological therapies that are effective in stowing or reversing atherosclerosis.

• 出版日期2008-7
• 单位西北大学