Molecular mechanisms of diabetic heart disease: Insights from transcriptomic technologies.

Marcella Conning-Rowland, Richard M Cubbon
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Abstract

Over half a billion adults across the world have diabetes mellitus (DM). This has a wide-ranging impact on their health, including more than doubling their risk of major cardiovascular events, in comparison to age-sex matched individuals without DM. Notably, the risk of heart failure is particularly increased, even when coronary artery disease and hypertension are not present. Macro- and micro-vascular complications related to endothelial cell (EC) dysfunction are a systemic feature of DM and can affect the heart. However, it remains unclear to what extent these and other factors underpin myocardial dysfunction and heart failure linked with DM. Use of unbiased 'omics approaches to profile the molecular environment of the heart offers an opportunity to identify novel drivers of cardiac dysfunction in DM. Multiple transcriptomics studies have characterised the whole myocardium or isolated cardiac ECs. We present a systematic summary of relevant studies, which identifies common themes including alterations in both myocardial fatty acid metabolism and inflammation. These findings prompt further research focussed on these processes to validate potentially causal factors for prioritisation into therapeutic development pipelines.

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糖尿病心脏病的分子机制:转录组技术带来的启示
全球有超过 5 亿成年人患有糖尿病(DM)。这对他们的健康产生了广泛的影响,包括与年龄性别匹配的非糖尿病患者相比,他们发生重大心血管事件的风险增加了一倍多。值得注意的是,即使没有冠状动脉疾病和高血压,发生心力衰竭的风险也会特别增加。与内皮细胞(EC)功能障碍有关的大血管和微血管并发症是糖尿病的一个全身性特征,并可影响心脏。然而,目前仍不清楚这些因素和其他因素在多大程度上支撑着与糖尿病相关的心肌功能障碍和心力衰竭。使用无偏见的'omics'方法来描述心脏的分子环境,为确定DM心脏功能障碍的新驱动因素提供了机会。多项转录组学研究描述了整个心肌或分离的心肌细胞的特征。我们对相关研究进行了系统总结,确定了包括心肌脂肪酸代谢和炎症改变在内的共同主题。这些发现促使我们进一步研究这些过程,以验证潜在的致病因素,并将其优先纳入治疗开发管道。
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