Sex differences in heart mitochondria regulate diastolic dysfunction.
Sex differences in heart mitochondria regulate diastolic dysfunction.
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DOI：
10.1038/s41467-022-31544-5
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发表时间：
2022-07-04
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
--
作者：
Heart failure with preserved ejection fraction (HFpEF) exhibits a sex bias, being more common in women than men, and we hypothesize that mitochondrial sex differences might underlie this bias. As part of genetic studies of heart failure in mice, we observe that heart mitochondrial DNA levels and function tend to be reduced in females as compared to males. We also observe that expression of genes encoding mitochondrial proteins are higher in males than females in human cohorts. We test our hypothesis in a panel of genetically diverse inbred strains of mice, termed the Hybrid Mouse Diversity Panel (HMDP). Indeed, we find that mitochondrial gene expression is highly correlated with diastolic function, a key trait in HFpEF. Consistent with this, studies of a “two-hit” mouse model of HFpEF confirm that mitochondrial function differs between sexes and is strongly associated with a number of HFpEF traits. By integrating data from human heart failure and the mouse HMDP cohort, we identify the mitochondrial gene Acsl6 as a genetic determinant of diastolic function. We validate its role in HFpEF using adenoviral over-expression in the heart. We conclude that sex differences in mitochondrial function underlie, in part, the sex bias in diastolic function. In this paper, the authors show that sex differences in mitochondrial DNA levels and function in the heart contribute to sex biases in functions relevant to heart failure, identifying Acsl6 as a mitochondrial sex-biased regulator of diastolic function.
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与性别相关的心力衰竭差异，保留的射血分数。
影响因子：
4.6
作者：
Duca F;Zotter-Tufaro C;Kammerlander AA;Aschauer S;Binder C;Mascherbauer J;Bonderman D
通讯作者：
Bonderman D
影响因子：
5
作者：
Chapski, Douglas J.;Cabaj, Maximilian;Morselli, Marco;Mason, Rosibel J.;Soehalim, Elizabeth;Ren, Shuxun;Pellegrini, Matteo;Wang, Yibin;Vondriska, Thomas M.;Rosa-Garrido, Manuel
通讯作者：
Rosa-Garrido, Manuel
影响因子：
5.2
作者：
John, Cathleen;Grune, Jana;Grune, Tilman
通讯作者：
Grune, Tilman
影响因子：
29
作者：
Parks BW;Sallam T;Mehrabian M;Psychogios N;Hui ST;Norheim F;Castellani LW;Rau CD;Pan C;Phun J;Zhou Z;Yang WP;Neuhaus I;Gargalovic PS;Kirchgessner TG;Graham M;Lee R;Tontonoz P;Gerszten RE;Hevener AL;Lusis AJ
通讯作者：
Lusis AJ
DOI：
10.1161/circheartfailure.112.972828
发表时间：
2013-03
期刊：
Circulation. Heart failure
影响因子：
--
作者：
Ho JE;Lyass A;Lee DS;Vasan RS;Kannel WB;Larson MG;Levy D
通讯作者：
Levy D