Ira Tabas , Kevin Jon Williams and Jan Borén and Therapeutic Implications Subendothelial Lipoprotein Retention as the Initiating Process in Atherosclerosis : Update
Ira Tabas , Kevin Jon Williams and Jan Borén and Therapeutic Implications Subendothelial Lipoprotein Retention as the Initiating Process in Atherosclerosis : Update
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发表时间：
2007
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通讯作者：
I. Tabas;K. Williams;J. Borén
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作者：
I. Tabas;K. Williams;J. Borén
动脉粥样硬化形成的关键启动过程是载脂蛋白b -含脂蛋白的内皮下滞留。对这些保留的脂蛋白的局部生物反应，包括慢性和适应性不良的巨噬细胞和t细胞主导的炎症反应，促进了随后的病变发展。迄今为止，最有效的治疗动脉粥样硬化性血栓性心血管疾病的方法是低密度降脂蛋白药物，其原理是减少循环载脂蛋白B脂蛋白降低它们进入并保留在内皮下层的可能性。该领域正在进行的改进包括更积极地降低血浆中的低密度脂蛋白和其他致动脉粥样硬化脂蛋白，以及在高危个体的早期开始低密度脂蛋白降低治疗。潜在的未来治疗方法包括尝试阻断载脂蛋白B脂蛋白与介导滞留的特定内皮下基质分子的相互作用，并干扰动脉壁内促进滞留的辅助分子，如脂蛋白脂肪酶、分泌鞘磷脂酶和分泌磷脂酶A2。虽然不是本综述的主要焦点，但针对残留脂蛋白的致动脉粥样硬化反应和促进去除残留脂蛋白的致动脉粥样硬化成分的治疗策略也很有希望。某些终生保持低血浆载脂蛋白B脂蛋白水平的人群患冠状动脉疾病的风险降低了90%，这一发现给我们带来了希望，我们对这一主要杀手的发病机制的进一步了解可能导致其根除。(循环。2007;116:1832 - 1844)。
The key initiating process in atherogenesis is the subendothelial retention of apolipoprotein B–containing lipoproteins. Local biological responses to these retained lipoproteins, including a chronic and maladaptive macrophageand T-cell–dominated inflammatory response, promote subsequent lesion development. The most effective therapy against atherothrombotic cardiovascular disease to date—low density lipoprotein–lowering drugs—is based on the principle that decreasing circulating apolipoprotein B lipoproteins decreases the probability that they will enter and be retained in the subendothelium. Ongoing improvements in this area include more aggressive lowering of low-density lipoprotein and other atherogenic lipoproteins in the plasma and initiation of low-density lipoprotein–lowering therapy at an earlier age in at-risk individuals. Potential future therapeutic approaches include attempts to block the interaction of apolipoprotein B lipoproteins with the specific subendothelial matrix molecules that mediate retention and to interfere with accessory molecules within the arterial wall that promote retention such as lipoprotein lipase, secretory sphingomyelinase, and secretory phospholipase A2. Although not the primary focus of this review, therapeutic strategies that target the proatherogenic responses to retained lipoproteins and that promote the removal of atherogenic components of retained lipoproteins also hold promise. The finding that certain human populations of individuals who maintain lifelong low plasma levels of apolipoprotein B lipoproteins have an 90% decreased risk of coronary artery disease gives hope that our further understanding of the pathogenesis of this leading killer could lead to its eradication. (Circulation. 2007;116:1832-1844.)