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DOI | 10.1038/nature22010 |
Nitrosative stress drives heart failure with preserved ejection fraction | |
Schiattarella, Gabriele G.1,2; Altamirano, Francisco1; Tong, Dan1; French, Kristin M.1; Villalobos, Elisa1; Kim, Soo Young1; Luo, Xiang1; Jiang, Nan1; May, Herman I.1; Wang, Zhao V.1; Hill, Theodore M.1; Mammen, Pradeep P. A.1; Huang, Jian1; Lee, Dong I.3; Hahn, Virginia S.3; Sharma, Kavita3; Kass, David A.3; Lavandero, Sergio1,4,5,6; Gillette, Thomas G.1; Hill, Joseph A.1,7 | |
2019-04-18 | |
发表期刊 | NATURE |
ISSN | 0028-0836 |
EISSN | 1476-4687 |
出版年 | 2019 |
卷号 | 568期号:7752页码:351-+ |
文章类型 | Article |
语种 | 英语 |
国家 | USA; Italy; Chile |
英文摘要 | Heart failure with preserved ejection fraction (HFpEF) is a common syndrome with high morbidity and mortality for which there are no evidence-based therapies. Here we report that concomitant metabolic and hypertensive stress in mice-elicited by a combination of high-fat diet and inhibition of constitutive nitric oxide synthase using N-omega-nitro-larginine methyl ester (L-NAME)-recapitulates the numerous systemic and cardiovascular features of HFpEF in humans. Expression of one of the unfolded protein response effectors, the spliced form of X-box-binding protein 1 (XBP1s), was reduced in the myocardium of our rodent model and in humans with HFpEF. Mechanistically, the decrease in XBP1s resulted from increased activity of inducible nitric oxide synthase (iNOS) and S-nitrosylation of the endonuclease inositol-requiring protein 1 alpha (IRE1 alpha), culminating in defective XBP1 splicing. Pharmacological or genetic suppression of iNOS, or cardiomyocyte-restricted overexpression of XBP1s, each ameliorated the HFpEF phenotype. We report that iNOS-driven dysregulation of the IRE1 alpha-XBP1 pathway is a crucial mechanism of cardiomyocyte dysfunction in HFpEF. |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000464950700047 |
WOS关键词 | NITRIC-OXIDE SYNTHASE ; S-NITROSYLATION ; DYSFUNCTION ; INHIBITION ; MODEL |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/202703 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.Univ Texas Southwestern Med Ctr Dallas, Dept Internal Med, Div Cardiol, Dallas, TX 75390 USA; 2.Univ Naples Federico II, Div Cardiol, Dept Adv Biomed Sci, Naples, Italy; 3.Johns Hopkins Sch Med, Div Cardiol, Dept Med, Baltimore, MD USA; 4.Univ Chile, Fac Chem & Pharmaceut Sci, Adv Ctr Chron Dis ACCDiS, Santiago, Chile; 5.Univ Chile, Fac Med, Santiago, Chile; 6.Univ Chile, Fac Med, Inst Biomed Sci ICBM, Ctr Mol Studies Cell CEMC, Santiago, Chile; 7.Univ Texas Southwestern Med Ctr Dallas, Dept Mol Biol, Dallas, TX 75390 USA |
推荐引用方式 GB/T 7714 | Schiattarella, Gabriele G.,Altamirano, Francisco,Tong, Dan,et al. Nitrosative stress drives heart failure with preserved ejection fraction[J]. NATURE,2019,568(7752):351-+. |
APA | Schiattarella, Gabriele G..,Altamirano, Francisco.,Tong, Dan.,French, Kristin M..,Villalobos, Elisa.,...&Hill, Joseph A..(2019).Nitrosative stress drives heart failure with preserved ejection fraction.NATURE,568(7752),351-+. |
MLA | Schiattarella, Gabriele G.,et al."Nitrosative stress drives heart failure with preserved ejection fraction".NATURE 568.7752(2019):351-+. |
条目包含的文件 | 条目无相关文件。 |
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