Berberine alleviates myocardial diastolic dysfunction by modulating Drp1-mediated mitochondrial fission and Ca2+ homeostasis in a murine model of HFpEF.
10.1007/s11684-023-0983-0
- Author:
Miyesaier ABUDUREYIMU
1
;
Mingjie YANG
2
;
Xiang WANG
1
;
Xuanming LUO
3
;
Junbo GE
4
;
Hu PENG
5
;
Yingmei ZHANG
6
;
Jun REN
7
Author Information
1. Cardiovascular Department, Shanghai Xuhui Central Hospital, Fudan University, Shanghai, 200031, China.
2. Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai, 200032, China.
3. Department of General Surgery, Shanghai Xuhui Central Hospital, Fudan University, Shanghai, 200031, China.
4. Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai, 200032, China. ge.junbo@zs-hospital.sh.cn.
5. Department of Geriatrics, Shanghai Tenth Hospital, Tongji University, Shanghai, 200072, China. penghu@tongji.edu.cn.
6. Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai, 200032, China. zhang.yingmei@zs-hospital.sh.cn.
7. Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai, 200032, China. ren.jun@zs-hospital.sh.cn.
- Publication Type:Journal Article
- Keywords:
Ca2+;
Drp1;
HFpEF;
autophagy;
berberine
- MeSH:
Male;
Mice;
Animals;
Heart Failure/drug therapy*;
Stroke Volume/physiology*;
Ventricular Function, Left/physiology*;
Berberine/therapeutic use*;
Disease Models, Animal;
Mitochondrial Dynamics;
Myocardium;
Homeostasis
- From:
Frontiers of Medicine
2023;17(6):1219-1235
- CountryChina
- Language:English
-
Abstract:
Heart failure with preserved ejection fraction (HFpEF) displays normal or near-normal left ventricular ejection fraction, diastolic dysfunction, cardiac hypertrophy, and poor exercise capacity. Berberine, an isoquinoline alkaloid, possesses cardiovascular benefits. Adult male mice were assigned to chow or high-fat diet with L-NAME ("two-hit" model) for 15 weeks. Diastolic function was assessed using echocardiography and noninvasive Doppler technique. Myocardial morphology, mitochondrial ultrastructure, and cardiomyocyte mechanical properties were evaluated. Proteomics analysis, autophagic flux, and intracellular Ca2+ were also assessed in chow and HFpEF mice. The results show exercise intolerance and cardiac diastolic dysfunction in "two-hit"-induced HFpEF model, in which unfavorable geometric changes such as increased cell size, interstitial fibrosis, and mitochondrial swelling occurred in the myocardium. Diastolic dysfunction was indicated by the elevated E value, mitral E/A ratio, and E/e' ratio, decreased e' value and maximal velocity of re-lengthening (-dL/dt), and prolonged re-lengthening in HFpEF mice. The effects of these processes were alleviated by berberine. Moreover, berberine ameliorated autophagic flux, alleviated Drp1 mitochondrial localization, mitochondrial Ca2+ overload and fragmentation, and promoted intracellular Ca2+ reuptake into sarcoplasmic reticulum by regulating phospholamban and SERCA2a. Finally, berberine alleviated diastolic dysfunction in "two-hit" diet-induced HFpEF model possibly because of the promotion of autophagic flux, inhibition of mitochondrial fragmentation, and cytosolic Ca2+ overload.
