Obesity, metabolic dysfunction, and cardiac fibrosis: pathophysiological pathways, molecular mechanisms, and therapeutic opportunities.
Obesity, metabolic dysfunction, and cardiac fibrosis: pathophysiological pathways, molecular mechanisms, and therapeutic opportunities.
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DOI：
10.1016/j.trsl.2014.05.001
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发表时间：
2014-10
期刊：
影响因子：
--
通讯作者：
Frangogiannis NG
中科院分区：
文献类型：
--
作者：
Cavalera M;Wang J;Frangogiannis NG
心脏纤维化与肥胖和代谢功能障碍密切相关，并可能导致肥胖者心力衰竭、房性心律失常和心脏性猝死的发生率增加。我们的综述讨论了肥胖与心肌纤维化在动物模型和人类患者中联系的证据，重点讨论了可能触发纤维化信号的基本病理生理变化，纤维化的细胞效应因子以及可能调节纤维化反应的分子信号。肥胖与广泛的病理生理改变(如压力和容量超负荷、代谢失调、神经体液激活和全身炎症)有关；它们在介导心脏纤维化中的相对作用尚不清楚。成纤维细胞的激活可能在肥胖相关的纤维化中起主要作用；然而，炎症细胞、心肌细胞和血管细胞也可能参与纤维化信号的传递。几个分子过程参与了肥胖症纤维化反应的调节。肾素-血管紧张素-醛固酮系统的激活、转化生长因子-β的诱导、氧化应激、晚期糖基化终末产物(AGEs)、内皮素-1、Rho-K信号转导、瘦素介导的作用以及基质细胞蛋白(如血栓反应蛋白-1)的上调可能在肥胖和代谢功能障碍模型的纤维化发展中发挥作用。此外，实验证据表明，肥胖和胰岛素抵抗深刻影响心脏损伤后的纤维化和重塑反应。了解肥胖相关纤维化所涉及的途径可能会导致开发新的治疗方法来预防肥胖症患者的心力衰竭和减轻心肌梗死后的心脏重构。
Cardiac fibrosis is strongly associated with obesity and metabolic dysfunction and may contribute to the increased incidence of heart failure, atrial arrhythmias and sudden cardiac death in obese subjects. Our review discusses the evidence linking obesity and myocardial fibrosis in animal models and human patients, focusing on the fundamental pathophysiologic alterations that may trigger fibrogenic signaling, the cellular effectors of fibrosis and the molecular signals that may regulate the fibrotic response. Obesity is associated with a wide range of pathophysiologic alterations (such as pressure and volume overload, metabolic dysregulation, neurohumoral activation and systemic inflammation); their relative role in mediating cardiac fibrosis is poorly defined. Activation of fibroblasts likely plays a major role in obesity-associated fibrosis; however, inflammatory cells, cardiomyocytes and vascular cells may also contribute to fibrogenic signaling. Several molecular processes have been implicated in regulation of the fibrotic response in obesity. Activation of the Renin-Angiotensin-Aldosterone System, induction of Transforming Growth Factor-β, oxidative stress, advanced glycation end-products (AGEs), endothelin-1, Rho-kinase signaling, leptin-mediated actions and upregulation of matricellular proteins (such as thrombospondin-1) may play a role in the development of fibrosis in models of obesity and metabolic dysfunction. Moreover, experimental evidence suggests that obesity and insulin resistance profoundly affect the fibrotic and remodeling response following cardiac injury. Understanding the pathways implicated in obesity-associated fibrosis may lead to development of novel therapies to prevent heart failure and to attenuate post-infarction cardiac remodeling in obese patients.
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影响因子：
5.5
作者：
Abed, Hany S.;Samuel, Chrishan S.;Sanders, Prashanthan
通讯作者：
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影响因子：
20.1
作者：
Dobaczewski M;Bujak M;Li N;Gonzalez-Quesada C;Mendoza LH;Wang XF;Frangogiannis NG
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DOI：
10.3109/08977194.2011.595714
发表时间：
2011-10
期刊：
Growth factors (Chur, Switzerland)
影响因子：
--
作者：
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通讯作者：
Frangogiannis NG
影响因子：
4.8
作者：
Aroor, Annayya R.;Sowers, James R.;DeMarco, Vincent G.
通讯作者：
DeMarco, Vincent G.
DOI：
10.1152/ajpheart.00514.2007
发表时间：
2007-09-01
影响因子：
4.8
作者：
Banerjee, Indroneal;Fuseler, John W.;Baudino, Troy A.
通讯作者：
Baudino, Troy A.