Type 2 Diabetes Mellitus and Cardiovascular Disease: Genetic and Epigenetic Links.
Type 2 Diabetes Mellitus and Cardiovascular Disease: Genetic and Epigenetic Links.
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2型糖尿病和心血管疾病：遗传和表观遗传联系。
DOI：
10.3389/fendo.2018.00002
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发表时间：
2018
影响因子：
5.2
通讯作者：
Foti DP
中科院分区：
文献类型：
--
作者：
De Rosa S;Arcidiacono B;Chiefari E;Brunetti A;Indolfi C;Foti DP
2型糖尿病（Type 2 diabetes mellitus，DM）是糖尿病性心肌病和动脉粥样硬化性心血管疾病（atherosclerotic cardiovascular disease，CVD）的常见代谢紊乱，可通过多种机制导致心力衰竭，包括心肌梗死和慢性压力超负荷。主要与高血糖症和慢性持续高胰岛素血症相关的致病机制包括代谢谱、细胞内信号传导途径、能量产生、氧化还原状态、对缺血的易感性增加和细胞外基质重塑的变化。2型糖尿病和心血管疾病之间的密切关系导致了共同的土壤假说，假设这两种情况有共同的遗传和环境因素影响这种关联。然而，尽管在大多数受影响的患者中可以确定CVD和2型DM的共同危险因素，如肥胖，胰岛素抵抗，血脂异常，炎症和血栓形成倾向，但对这些因素如何影响这两种情况知之甚少，因此仍然需要努力更全面地了解这种关系。2型糖尿病和心血管疾病的遗传、表观遗传和环境背景最近已被研究和更新。然而，潜在的发病机制很少在更广泛的共同背景下进行研究，而是在2型DM或CVD的特定背景下分别进行研究。由于2型糖尿病和心血管疾病之间的确切病理生理联系尚未完全了解，许多方面仍然需要阐明，这两种疾病的伴随发展所涉及的遗传，表观遗传和环境影响的综合描述是至关重要的，以揭示2型糖尿病和心血管疾病之间的相互联系。本文综述了2型糖尿病和心血管疾病中重叠的遗传和表观遗传方面的现有知识，包括microRNA和长非编码RNA，其异常调节与这两种疾病有关，无论是病因学上还是其进展的原因。了解这些疾病之间的联系可能有助于推动未来的研究走向一个综合的病理生理学方法，并提供该领域的未来方向。
Type 2 diabetes mellitus (DM) is a common metabolic disorder predisposing to diabetic cardiomyopathy and atherosclerotic cardiovascular disease (CVD), which could lead to heart failure through a variety of mechanisms, including myocardial infarction and chronic pressure overload. Pathogenetic mechanisms, mainly linked to hyperglycemia and chronic sustained hyperinsulinemia, include changes in metabolic profiles, intracellular signaling pathways, energy production, redox status, increased susceptibility to ischemia, and extracellular matrix remodeling. The close relationship between type 2 DM and CVD has led to the common soil hypothesis, postulating that both conditions share common genetic and environmental factors influencing this association. However, although the common risk factors of both CVD and type 2 DM, such as obesity, insulin resistance, dyslipidemia, inflammation, and thrombophilia, can be identified in the majority of affected patients, less is known about how these factors influence both conditions, so that efforts are still needed for a more comprehensive understanding of this relationship. The genetic, epigenetic, and environmental backgrounds of both type 2 DM and CVD have been more recently studied and updated. However, the underlying pathogenetic mechanisms have seldom been investigated within the broader shared background, but rather studied in the specific context of type 2 DM or CVD, separately. As the precise pathophysiological links between type 2 DM and CVD are not entirely understood and many aspects still require elucidation, an integrated description of the genetic, epigenetic, and environmental influences involved in the concomitant development of both diseases is of paramount importance to shed new light on the interlinks between type 2 DM and CVD. This review addresses the current knowledge of overlapping genetic and epigenetic aspects in type 2 DM and CVD, including microRNAs and long non-coding RNAs, whose abnormal regulation has been implicated in both disease conditions, either etiologically or as cause for their progression. Understanding the links between these disorders may help to drive future research toward an integrated pathophysiological approach and to provide future directions in the field.