Publication Name	World Journal of Cardiology
Manuscript ID	116558
Country	China

Category	Cardiac & Cardiovascular Systems
Manuscript Type	Letter to the Editor
Article Title	Ca2+/calmodulin-dependent protein kinase II in heart failure and the role of sodium-glucose-cotransporter 2 inhibitors
Manuscript Source	Unsolicited Manuscript
All Author List	Yi-Fei Zhang, Wu-Xiao Yang and Xue-Wen Li
Funding Agency and Grant Number	Funding Agency Grant Number National Natural Science Foundation of China No. 8217022047
Corresponding Author	Xue-Wen Li, Chief Physician, PhD, Professor, Department of Cardiology, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, No. 99 Longcheng Street, Taiyuan 030032, Shanxi Province, China. xuewenli1010@126.com
Key Words	Sodium-glucose cotransporter 2 inhibitor; Heart failure; Ca2+/calmodulin-dependent protein kinase II; Oxidative stress; Calcium homeostasis
Core Tip	Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have revolutionized the treatment of heart failure, but their direct molecular effects in cardiomyocytes, which express little sodium-glucose cotransporter-2, have not been fully described. This letter summarizes current evidence and presents a conceptual framework in which Ca2+/calmodulin-dependent protein kinase II is a central target. We hypothesize that many of the cardioprotective effects of SGLT2i are mediated by the dampening of Ca2+/calmodulin-dependent protein kinase II activity through synergistic modulation of ionic balance, relief of oxidative stress and inflammatory signaling suppression. Together, these processes may provide a unified explanation for the observed improvements in electrical stability, ventricular performance, and cardiac remodeling associated with SGLT2i treatment.
Citation	Zhang YF, Yang WX, Li XW. Ca2+/calmodulin-dependent protein kinase II in heart failure and the role of sodium-glucose-cotransporter 2 inhibitors. World J Cardiol 2026; In press

Received	2025-11-14 11:40
Peer-Review Started	2025-11-17 00:36
First Decision by Editorial Office Director	2025-11-26 08:19
Return for Revision	2025-11-26 08:19
Revised	2025-12-04 16:34
Publication Fee Transferred
Second Decision by Editor	2026-01-08 02:37
Second Decision by Editor-in-Chief
Final Decision by Editorial Office Director	2026-01-08 11:12
Articles in Press	2026-01-08 11:12
Edit the Manuscript by Language Editor
Typeset the Manuscript

ISSN	1949-8462 (online)
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