Molecular mechanisms and genetic regulation in atherosclerosis.
Molecular mechanisms and genetic regulation in atherosclerosis.
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DOI：
10.1016/j.ijcha.2018.09.006
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发表时间：
2018-12
期刊：
影响因子：
--
通讯作者：
Long S
中科院分区：
文献类型：
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作者：
Jackson AO;Regine MA;Subrata C;Long S
动脉粥样硬化（AS）表现为大至中等尺寸动脉的内膜和中膜中的脂质积聚、细胞外基质蛋白沉积和钙化，从而促进动脉僵硬和弹性降低。AS在全球范围内导致发病率和死亡率增加已被公认。近年来的研究表明，遗传异常在AS的发生发展中起重要作用。已发现特异性基因突变和组蛋白修饰可诱导AS形成。此外，特定的RNA，如microRNA和环状RNA已被确定在AS的进展中发挥关键作用。然而，基因突变、DNA和组蛋白修饰、microRNA和环状RNA诱导AS的机制仍不清楚。本文综述了基因突变、DNA和组蛋白修饰、microRNA和环状RNA等在AS发病中的作用机制。本综述进一步为AS的治疗提供了一个以遗传机制为靶点的治疗策略方向。DNA和组蛋白修饰促进动脉粥样硬化中的转录变化。基因突变引起血脂异常和高血糖，促进动脉粥样硬化。miRNAs和cirRNA参与动脉粥样硬化的发展。基因突变相关的氧化应激和改变炎症和营养因素促进动脉粥样硬化。
Atherosclerosis (AS) manifested by lipid accumulation, extracellular matrix protein deposition, and calcification in the intima and media of the large to medium size arteries promoting arterial stiffness and reduction of elasticity. It has been accepted that AS leads to increased morbidity and mortality worldwide. Recent studies indicated that genetic abnormalities play an important role in the development of AS. Specific genetic mutation and histone modification have been found to induce AS formation. Furthermore, specific RNAs such as microRNAs and circular RNAs have been identified to play a crucial role in the progression of AS. Nevertheless, the mechanisms by which genetic mutation, DNA and histone modification, microRNAs and circular RNA induce AS still remain elusive. This review describes specific mechanisms and pathways through which genetic mutation, DNA and histone modification, microRNAs and circular RNA instigate AS. This review further provides a therapeutic strategic direction for the treatment of AS targeting genetic mechanisms. DNA and histone modifications promote transcriptional changes in atherosclerosis. Gene mutations cause dyslipidemia and hyperglycemia to promote atherosclerosis. miRNAs and cirRNA are involved in the development of atherosclerosis. Gene mutations associated oxidative stress and altered inflammatory and nutritive factors promote atherosclerosis.