{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T10:09:22Z","timestamp":1788775762580,"version":"build-2803163510"},"reference-count":180,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:p>\n                    Cardiovascular diseases rank as the global primary cause of mortality. Heart failure (HF) represents a progressive cardiac syndrome triggered by structural or functional myocardial damage that compromises ventricular systolic output. Intracellular calcium homeostasis underpins cardiomyocyte excitation-contraction coupling. Calcium overload and dysregulated calcium handling act as central pathogenic forces driving HF progression. Sympathetic \u03b2\n                    <jats:sub>1<\/jats:sub>\n                    -adrenergic receptor (\u03b2\n                    <jats:sub>1<\/jats:sub>\n                    -AR) and parasympathetic M\n                    <jats:sub>2<\/jats:sub>\n                    muscarinic acetylcholine receptor (M\n                    <jats:sub>2<\/jats:sub>\n                    -AChR) coordinate dual regulatory signaling to control cardiac calcium turnover, alongside key modulators including L-type calcium channel (LTCC), ryanodine receptor 2 (RyR2), SERCA2a, cardiac troponin C (cTnC), Na\n                    <jats:sup>+<\/jats:sup>\n                    \/Ca\n                    <jats:sup>2+<\/jats:sup>\n                    exchanger 1 (NCX1) and mitochondrial permeability transition pore (MPTP). This review outlines physiological calcium cycling and systematically characterizes HF-related functional defects of calcium regulatory machinery from three layers: calcium release, sarcoplasmic reticulum calcium reuptake and auxiliary calcium mediators. We further discuss the underlying mechanisms of calcium-targeted pharmaceuticals and gene therapeutic approaches, while addressing translational bottlenecks limiting single-target interventions. Restoration of balanced cytosolic calcium cycling holds therapeutic potential to reverse pathological myocardial remodeling in HF.\n                  <\/jats:p>","DOI":"10.3389\/fcvm.2026.1938059","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T05:22:19Z","timestamp":1788412939000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Aberrant myocardial calcium cycling: pathogenic mechanisms and targeted therapeutics for heart failure"],"prefix":"10.3389","volume":"13","author":[{"given":"Chunxiao","family":"Zhao","sequence":"first","affiliation":[{"name":"The Affiliated Hospital of Shandong University of Traditional Chinese Medicine","place":["Jinan, Shandong, China"]},{"name":"Shandong University of Traditional Chinese Medicine","place":["Jinan, Shandong, China"]},{"name":"Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahao","family":"Liu","sequence":"additional","affiliation":[{"name":"Jinan Municipal Government Hospital","place":["Jinan, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juanjuan","family":"Xin","sequence":"additional","affiliation":[{"name":"Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qun","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaochun","family":"Yu","sequence":"additional","affiliation":[{"name":"Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junhong","family":"Gao","sequence":"additional","affiliation":[{"name":"Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1614","DOI":"10.1016\/j.ehj.2004.06.038","article-title":"Quantifying the heart failure epidemic: prevalence, incidence rate, lifetime risk and prognosis of heart failure the rotterdam study","volume":"25","author":"Bleumink","year":"2004","journal-title":"Eur Heart J"},{"key":"B2","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1002\/ejhf.483","article-title":"Epidemiology of heart failure: the prevalence of heart failure and ventricular dysfunction in older adults over time. 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