Targeting the vasculature in cardiometabolic disease.
Targeting the vasculature in cardiometabolic disease.
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DOI：
10.1172/jci148556
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发表时间：
2022-03-15
期刊：
影响因子：
--
通讯作者：
Sessa WC
中科院分区：
文献类型：
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作者：
Boutagy NE;Singh AK;Sessa WC
肥胖已经达到流行病的比例，是胰岛素抵抗（IR）和2型糖尿病（T2 D）的主要贡献者。重要的是，IR和T2 D显著增加心血管（CV）疾病的风险。虽然有成功的方法来维持血糖控制，但与代谢疾病相关的CV发病率和死亡率仍在增加。因此，迫切需要了解肥胖期间发生的心脏代谢变化背后的细胞和分子过程，以便可以设计最佳的医学疗法来减轻或预防这种疾病的后遗症。血管内皮与循环环境持续接触;因此，肥胖驱动的脂质、葡萄糖和促炎介质升高诱导血管系统所有节段的内皮功能障碍、血管炎症和血管重塑并不奇怪。随着心脏代谢疾病的进展，整个血管网络的病理变化也会发生，这可能会加剧疾病的进展。最近的细胞和分子数据表明，血管系统是几种心脏代谢疾病发展的起始和诱发因素。本文综述了动脉粥样硬化、IR和T2 D以及射血分数正常的心力衰竭的背景下的这些发现。此外，还介绍了治疗靶向血管系统以减轻心脏代谢疾病负担的新策略。
Obesity has reached epidemic proportions and is a major contributor to insulin resistance (IR) and type 2 diabetes (T2D). Importantly, IR and T2D substantially increase the risk of cardiovascular (CV) disease. Although there are successful approaches to maintain glycemic control, there continue to be increased CV morbidity and mortality associated with metabolic disease. Therefore, there is an urgent need to understand the cellular and molecular processes that underlie cardiometabolic changes that occur during obesity so that optimal medical therapies can be designed to attenuate or prevent the sequelae of this disease. The vascular endothelium is in constant contact with the circulating milieu; thus, it is not surprising that obesity-driven elevations in lipids, glucose, and proinflammatory mediators induce endothelial dysfunction, vascular inflammation, and vascular remodeling in all segments of the vasculature. As cardiometabolic disease progresses, so do pathological changes in the entire vascular network, which can feed forward to exacerbate disease progression. Recent cellular and molecular data have implicated the vasculature as an initiating and instigating factor in the development of several cardiometabolic diseases. This Review discusses these findings in the context of atherosclerosis, IR and T2D, and heart failure with preserved ejection fraction. In addition, novel strategies to therapeutically target the vasculature to lessen cardiometabolic disease burden are introduced.