Muscular changes in animal models of heart failure with preserved ejection fraction: what comes closest to the patient?

被引：20

作者：

Goto, Keita ^{[1
]}

Schauer, Antje ^{[1
]}

Augstein, Antje ^{[1
]}

Methawasin, Mei ^{[2
]}

Granzier, Henk ^{[2
]}

Halle, Martin ^{[3
,4
]}

Van Craenenbroeck, Emeline M. ^{[5
]}

Rolim, Natale ^{[6
]}

Gielen, Stephan ^{[7
]}

Pieske, Burkert ^{[8
]}

Winzer, Ephraim B. ^{[1
]}

Linke, Axel ^{[1
,9
,10
]}

Adams, Volker ^{[1
,9
,10
]}

机构：

[1] Tech Univ Dresden, Ctr Heart, Dresden Univ Hosp, Lab Expt & Mol Cardiol,Dept Internal Med & Cardio, Fetscherstr 76, D-01307 Dresden, Germany

[2] Univ Arizona, Dept Cellular & Mol Med, Tucson, AZ USA

[3] Tech Univ Munich, Prevent & Sports Med, Klinikum Rechts Isar, Munich, Germany

[4] DZHK German Ctr Cardiovasc Res, Munich Heart Alliance, Partner Site, Munich, Germany

[5] Antwerp Univ Hosp, GENCOR Dept, Res Grp Cardiovasc Dis, Edegem, Belgium

[6] NTNU, KG Jebsen Ctr Exercise Med, Fac Med, Dept Circulat & Med Imaging, Trondheim, Norway

[7] Klinikum Lippe, Dept Cardiol Angiol & Intens Care, Detmold, Germany

[8] Charite Univ Med Berlin, Campus Virchow Klinikum, Dept Internal Med & Cardiol, Berlin, Germany

[9] Dresden Cardiovasc Res Inst, Dresden, Germany

[10] Core Labs GmbH, Dresden, Germany

来源：

ESC HEART FAILURE | 2021年 / 8卷 / 01期

关键词：

Skeletal muscle; Heart failure with preserved ejection fraction; Animal models; HUMAN SKELETAL-MUSCLE; MYOSIN HEAVY-CHAIN; QUALITY-OF-LIFE; EXERCISE INTOLERANCE; DIASTOLIC FUNCTION; OLDER PATIENTS; MITOCHONDRIAL; EXPRESSION; CAPACITY; RAT;

D O I：

10.1002/ehf2.13142

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Aims Heart failure with preserved ejection fraction (HFpEF) is associated with reduced exercise capacity elicited by skeletal muscle (SM) alterations. Up to now, no clear medical treatment advice for HFpEF is available. Identification of the ideal animal model mimicking the human condition is a critical step in developing and testing treatment strategies. Several HFpEF animals have been described, but the most suitable in terms of comparability with SM alterations in HFpEF patients is unclear. The aim of the present study was to investigate molecular changes in SM of three different animal models and to compare them with alterations of muscle biopsies obtained from human HFpEF patients. Methods and results Skeletal muscle tissue was obtained from HFpEF and control patients and from three different animal models including the respective controls-ZSF1 rat, Dahl salt-sensitive rat, and transverse aortic constriction surgery/deoxycorticosterone mouse. The development of HFpEF was verified by echocardiography. Protein expression and enzyme activity of selected markers were assessed in SM tissue homogenates. Protein expression between SM tissue obtained from HFpEF patients and the ZSF1 rats revealed similarities for protein markers involved in muscle atrophy (MuRF1 expression, protein ubiquitinylation, and LC3) and mitochondrial metabolism (succinate dehydrogenase and malate dehydrogenase activity, porin expression). The other two animal models exhibited far less similarities to the human samples. Conclusions None of the three tested animal models mimics the condition in HFpEF patients completely, but among the animal models tested, the ZSF1 rat (ZSF1-lean vs. ZSF1-obese) shows the highest overlap to the human condition. Therefore, when studying therapeutic interventions to treat HFpEF and especially alterations in the SM, we suggest that the ZSF1 rat is a suitable model.

引用

页码：139 / 150

页数：12

共 52 条

[21] Effects of endurance training on mitochondrial ultrastructure and fiber type distribution in skeletal muscle of patients with stable chronic heart failure [J].