Primary Prevention of Atherosclerosis A Clinical Challenge for the Reversal of Epigenetic Mechanisms?
Primary Prevention of Atherosclerosis A Clinical Challenge for the Reversal of Epigenetic Mechanisms?
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DOI：
10.1161/circulationaha.111.085787
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发表时间：
2012-05-15
期刊：
影响因子：
37.8
通讯作者：
Mancini, Francesco P.
中科院分区：
文献类型：
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作者：
Napoli, Claudio;Crudele, Valeria;Mancini, Francesco P.
尽管血清低密度脂蛋白胆固醇（LDL-C）水平升高是该疾病发病的主要原因，但正如大量极好的流行病学、临床和实验研究所确定的，重要的新因素已进入致动脉粥样硬化过程的竞技场。除了历史上的氧化假说，即氧化LDL通过逃避稳态机制，强烈加速斑块形成，最近的证据表明血管炎症和细胞凋亡是动脉粥样硬化进展的关键因素。1-3该疾病还与免疫细胞的内膜下浸润和由心血管危险因素诱导的内皮功能障碍有关。目前，内皮功能障碍被认为是血管损伤的第一阶段和动脉粥样硬化形成的早期事件之一。1-3遗传和环境来源的病因和致病因素共同作用，促进局部和全身效应，导致动脉粥样硬化疾病的发作、进展和最终结局。动脉粥样硬化、心肌梗死、中风和外周动脉疾病的临床后遗症取决于受累的血管区域，而受累的血管区域又取决于复杂的基因-环境相互作用，尽管临床症状突然出现，但动脉粥样硬化的演变非常缓慢，这为早期诊断提供了机会。事实上，该领域的一个突破是认识到，虽然动脉粥样硬化产生严重的疾病，最常见的影响中年人到老年人，动脉粥样硬化形成在生命的早期就开始了，甚至在胎儿阶段。4，5任何疾病的一级预防如果开始得越早越有效。因此，识别高危个体并及时启动一级预防至关重要，特别是对于动脉粥样硬化，其甚至在出生前就可以开始缓慢但无情地损害动脉壁。表观遗传机制最近被认为是可能的模式-
Although elevated levels of serum low-density lipoprotein cholesterol (LDL-C) are the major cause of onset of the disease, as established by a large number of superb epidemiological, clinical, and experimental studies, important novel factors have entered the arena of the atherogenic process. Besides the historical oxidative hypothesis that states that oxidized LDL, by escaping the homeostatic mechanism, strongly accelerates plaque formation, more recent evidence has given credit to vascular inflammation and apoptosis as crucial players in the progression of atherosclerosis. 1–3 The disease has also been linked to the subintimal infiltration of immune cells and endothelial dysfunction induced by cardiovascular risk factors. Currently, endothelial dysfunction is considered one of the first stages of vascular damage and an early event in atherogenesis. 1–3 Etiologic and pathogenetic factors, of both genetic and environmental origin, act together to promote local and systemic effects that lead to the onset, progression, and final outcome of the atherosclerotic disease. The clinical sequelae of atherosclerosis, myocardial infarction, stroke, and peripheral arterial disease depend on the affected vascular district, which in turn depends on complex gene-environment interplay.Despite the sudden occurrence of clinical symptoms, however, the evolution of atherosclerosis is very slow, which provides an opportunity for early diagnosis. In fact, a breakthrough in the field has been to recognize that although atherosclerosis generates severe diseases that most frequently affect middle-aged to old people, atherogenesis begins very early in life, even at the fetal stage. 4, 5 Primary prevention of any disease is more effective if started sooner. Therefore, it is of paramount importance to identify high-risk individuals and to initiate primary prevention in a timely manner, especially for atherosclerosis, which can begin its slow but relentless damage of the arterial wall even before birth. Epigenetic mechanisms have been recognized recently as possible mod-