Non-conventional genetic risk factors for cardiovascular disease.
Non-conventional genetic risk factors for cardiovascular disease.
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心血管疾病的非常规遗传危险因素。
DOI：
10.1159/000152922
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发表时间：
2008
影响因子：
--
通讯作者：
Allayee,Hooman
中科院分区：
文献类型：
--
作者：
Allayee,Hooman
心血管疾病（CVD），广义上定义为包括心肌梗死（MI）、冠状动脉疾病（CAD）、中风和动脉粥样硬化替代标志物（如颈动脉内膜中层厚度（IMT）和冠状动脉钙化（CAC））在内的疾病状态谱，是西方社会的主要死亡原因，在其他欠发达国家也越来越常见。CVD对医疗费用和患者生活质量造成的巨大负担需要开发新的更好的治疗方法，这些方法可以作为替代药物或与现有药物联合使用。动脉粥样硬化是CVD的最常见原因，是一种进行性疾病，其特征在于大动脉中脂质和纤维元素的积聚[1]。这是一个涉及许多因子和介质的复杂过程，并且基于驻留细胞（例如内皮细胞、平滑肌细胞和浸润性单核细胞/巨噬细胞和淋巴细胞）之间的动态信号交换。致动脉粥样硬化过程是由低密度脂蛋白（LDL）颗粒在动脉壁内皮下层的积累引发的，在那里它们被细胞衍生的活性氧氧化（图1，步骤I）。由内皮细胞产生的粘附分子、趋化因子和生长因子导致主要由单核细胞组成的炎性细胞粘附到血管壁并迁移到内皮下空间。在这种微环境中，活化的单核细胞增殖并分化为巨噬细胞，巨噬细胞开始吞噬氧化的LDL颗粒，随后转化为泡沫细胞（图1，步骤II）。伴随着细胞外脂质和内膜
Cardiovascular disease (CVD), defined broadly as the spectrum of disease states including myocardial infarction (MI), coronary artery disease (CAD), stroke, and surrogate markers of atherosclerosis such as carotid intima-media thickness (IMT) and coronary artery calcification (CAC), is the leading cause of death in Western societies and is becoming increasingly common in other less developed countries as well. The tremendous burden that CVD poses on healthcare costs and patients’ quality of life necessitates the development of novel and better treatments that can be used either as alternative medications or in conjunction with already existing drugs. Atherosclerosis, the most common cause of CVD, is a progressive disease characterized by the accumulation of lipids and fibrous elements in large arteries [1]. It is a complex process involving numerous factors and mediators and is based on the dynamic exchange of signals between resident cells, such as endothelial cells, smooth muscle cells, and infiltrating monocyte/macrophages and lymphocytes. The atherogenic process is initiated by the accumulation of low density lipoprotein (LDL) particles in the subendothelial layer of the artery wall, where they are oxidized by cell-derived reactive oxygen species (fig. 1, step I). The resulting production of adhesion molecules, chemokines, and growth factors by endothelial cells causes inflammatory cells, comprised predominantly of monocytes, to adhere to the vessel wall and migrate into the subendothelial space. In this microenvironment, the activated monocytes proliferate and differentiate into macrophages, which begin to engulf the oxidized LDL particles and subsequently transform into foam cells (fig. 1, step II). Accompanied by a progressive increase in extracellular lipids and intimal