Hydrogen sulfide attenuates high fat diet-induced cardiac dysfunction via the suppression of endoplasmic reticulum stress.
Hydrogen sulfide attenuates high fat diet-induced cardiac dysfunction via the suppression of endoplasmic reticulum stress.
复制标题
硫化氢通过抑制内质网应激，减轻高脂饮食诱导的心脏功能障碍。
DOI：
10.1016/j.niox.2014.12.013
复制
发表时间：
2015-04-30
影响因子：
3.9
通讯作者：
Calvert, John W.
中科院分区：
文献类型：
--
作者：
Barr, Larry A.;Shimizu, Yuuki;Lambert, Jonathan P.;Nicholson, Chad K.;Calvert, John W.
糖尿病性心肌病是与糖尿病和代谢综合征相关的发病率和死亡率的重要因素。然而，导致其发展的潜在分子机制尚未完全阐明。硫化氢（H2S）是一种内源性产生的信号分子，对调节心血管稳态至关重要。最近，旨在提高其水平的治疗策略已被证明在急性心肌缺血再灌注损伤和心力衰竭模型中具有心脏保护作用。H2S在糖尿病性心肌病发病机制中的确切作用尚未确定。因此，本研究的目的是评估高脂肪饮食（HFD）诱导的心肌病小鼠模型中循环和心脏H2S水平。用HFD（60%脂肪）饲料喂养小鼠24周，产生糖尿病性心肌病。HFD喂养降低了循环和心脏H2S，并诱导了2型糖尿病的标志特征。我们还观察到明显的心功能障碍，心脏增大，心脏肥大和纤维化的证据。H2S治疗（SG-1002，一种口服活性H2S供体）恢复了硫化物水平，改善了由HFD喂养引起的一些代谢紊乱，并减轻了HFD引起的心功能障碍。进一步的分析显示，H2S治疗恢复了脂联素水平，抑制了HFD喂养引起的心脏内质网应激。这些结果表明，循环和心脏H2S水平的降低在hfd诱导的心肌病的病理生理中起作用。此外，这些结果表明H2S治疗在治疗糖尿病引起的心血管并发症方面可能具有临床重要性。
Diabetic cardiomyopathy is a significant contributor to the morbidity and mortality associated with diabetes and metabolic syndrome. However, the underlying molecular mechanisms that lead to its development have not been fully elucidated. Hydrogen sulfide (H2S) is an endogenously produced signaling molecule that is critical for the regulation of cardiovascular homeostasis. Recently, therapeutic strategies aimed at increasing its levels have proven cardioprotective in models of acute myocardial ischemia-reperfusion injury and heart failure. The precise role of H2S in the pathogenesis of diabetic cardiomyopathy has not yet been established. Therefore, the goal of the present study was to evaluate circulating and cardiac H2S levels in a murine model of high fat diet (HFD)-induced cardiomyopathy. Diabetic cardiomyopathy was produced by feeding mice HFD (60% fat) chow for 24 weeks. HFD feeding reduced both circulating and cardiac H2S and induced hallmark features of type-2 diabetes. We also observed marked cardiac dysfunction, evidence of cardiac enlargement, cardiac hypertrophy, and fibrosis. H2S therapy (SG-1002, an orally active H2S donor) restored sulfide levels, improved some of the metabolic perturbations stemming from HFD feeding, and attenuated HFD-induced cardiac dysfunction. Additional analysis revealed that H2S therapy restored adiponectin levels and suppressed cardiac ER stress stemming from HFD feeding. These results suggest that diminished circulating and cardiac H2S levels play a role in the pathophysiology of HFD-induced cardiomyopathy. Additionally, these results suggest that H2S therapy may be of clinical importance in the treatment of cardiovascular complications stemming from diabetes.
登录
查看更多内容
影响因子：
16.6
作者：
Back SH;Kaufman RJ
通讯作者：
Kaufman RJ
影响因子：
20.1
作者：
Calvert JW;Jha S;Gundewar S;Elrod JW;Ramachandran A;Pattillo CB;Kevil CG;Lefer DJ
通讯作者：
Lefer DJ
影响因子：
37.8
作者：
Calvert JW;Elston M;Nicholson CK;Gundewar S;Jha S;Elrod JW;Ramachandran A;Lefer DJ
通讯作者：
Lefer DJ
影响因子：
7.7
作者：
Li J;Zhu H;Shen E;Wan L;Arnold JM;Peng T
通讯作者：
Peng T
影响因子：
5.6
作者：
Bousette, Nicolas;Abbasi, Cynthia;Gramolini, Anthony O.
通讯作者：
Gramolini, Anthony O.