SERCA2a dysfunction in the pathophysiology of heart failure with preserved ejection fraction: a direct role is yet to be established

被引:1
作者
Shooshtarian, Adam Kia [1 ]
O'Gallagher, Kevin [1 ]
Shah, Ajay M. [1 ]
Zhang, Min [1 ]
机构
[1] Kings Coll London, British Heart Fdn Ctr Res Excellence, Sch Cardiovasc & Metab Med & Sci, London, England
关键词
Heart failure; Ejection fraction; SERCA2a; Diastolic dysfunction; Calcium regulation; SARCOPLASMIC-RETICULUM CA2+-ATPASE; VENTRICULAR DIASTOLIC DYSFUNCTION; GENE-TRANSFER; PHOSPHOLAMBAN PHOSPHORYLATION; CARDIOMYOCYTE DYSFUNCTION; DILATED CARDIOMYOPATHY; CARDIAC-PERFORMANCE; CONTRACTILE RESERVE; MYOCARDIAL-FUNCTION; OXIDATIVE STRESS;
D O I
10.1007/s10741-025-10487-1
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
With rising incidence, mortality and limited therapeutic options, heart failure with preserved ejection fraction (HFpEF) remains one of the most important topics in cardiovascular medicine today. Characterised by left ventricular diastolic dysfunction partially due to impaired Ca2+ homeostasis, one ion channel in particular, SarcoEndoplasmic Reticulum Ca2+-ATPase (SERCA2a), may play a significant role in its pathophysiology. A better understanding of the complex mechanisms interplaying to contribute to SERCA2a dysfunction will help develop treatments targeting it and thus address the growing clinical challenge HFpEF poses. This review examines the conflicting evidence present for changes in SERCA2a expression and activity in HFpEF, explores potential underlying mechanisms, and finally evaluates the drug and gene therapy trials targeting SERCA2a in heart failure. Recent positive results from trials involving widely used anti-diabetic agents such as sodium-glucose co-transporter protein 2 inhibitors (SGLT2i) and glucagon-like peptide-1 (GLP-1) agonists offer advancement in HFpEF management. The potential interplay between these agents and SERCA2a regulation presents a novel angle that could open new avenues for modulating diastolic function; however, the mechanistic research in this emerging field is limited. Overall, the direct role of SERCA2a dysfunction in HFpEF remains undetermined, highlighting the need for well-designed pre-clinical studies and robust clinical trials.
引用
收藏
页码:545 / 564
页数:20
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