{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:45:27Z","timestamp":1791927927157,"version":"4.3.4"},"reference-count":29,"publisher":"American Physiological Society","issue":"5","license":[{"start":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T00:00:00Z","timestamp":1754956800000},"content-version":"vor","delay-in-days":223,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01-HL147263"],"award-info":[{"award-number":["R01-HL147263"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01-HL162825"],"award-info":[{"award-number":["R01-HL162825"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["2R01HL121700-06A1"],"award-info":[{"award-number":["2R01HL121700-06A1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R01HL172834-01"],"award-info":[{"award-number":["1R01HL172834-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"VA Merit","award":["IK6BX005753"],"award-info":[{"award-number":["IK6BX005753"]}]},{"name":"VA Merit","award":["I01BX005100"],"award-info":[{"award-number":["I01BX005100"]}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["24TPA1303770"],"award-info":[{"award-number":["24TPA1303770"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["25EIA1422015"],"award-info":[{"award-number":["25EIA1422015"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Abnormalities of Ca2+ signaling in the heart lead to common cardiac remodeling in the pathogenesis of cardiovascular disorders. The activation of calmodulin-dependent protein kinase II (CaMKII) is regulated by elevated intracellular Ca2+ level in cardiomyocytes, driving the progression of myocardial dysfunction. In this study, using models of \u03b22 adrenergic receptor (\u03b22AR) deficiency in cardiomyocytes (\u03b22AR-CKO), we observed an increased phosphorylation of CaMKII and upregulation of gene expression and protein level of the fibrotic marker connective tissue growth factor (CTGF) in the myocytes. In vivo treatment with the CaMKII inhibitor KN93 attenuated the upregulation of CTGF protein expression in \u03b22AR-CKO hearts. Enhanced L-type calcium channel (LTCC) current was observed in \u03b22AR-CKO cardiomyocytes following adrenergic stimulation, indicating a disruption of Ca2+ signaling. Treatment with the LTCC blocker nifedipine attenuated CaMKII activity and the expression of CTGF in \u03b22AR-CKO hearts, confirming the upstream role of abnormal LTCC-Ca2+ signaling. Additionally, 8-month-old \u03b22AR-CKO mice exhibited cardiac fibrosis and diastolic dysfunction. One month of in vivo nifedipine treatment improved both cardiac dysfunction and fibrosis in \u03b22AR-CKO mice. These findings highlight the critical role of cardiomyocyte \u03b22AR in maintaining LTCC-Ca2+ homeostasis. Loss of \u03b22AR amplifies the Ca2+-CaMKII axis, promoting fibrosis and cardiomyopathy in aging hearts.<\/jats:p>","DOI":"10.1093\/function\/zqaf036","type":"journal-article","created":{"date-parts":[[2025,8,9]],"date-time":"2025-08-09T11:37:47Z","timestamp":1754739467000},"source":"Crossref","is-referenced-by-count":2,"title":["Cardiac \u03b22 adrenergic receptor deletion drives calmodulin kinase II upregulation to induce connective tissue growth factor in cardiac fibrosis and diastolic dysfunction"],"prefix":"10.1152","volume":"6","author":[{"given":"Chaoqun","family":"Zhu","sequence":"first","affiliation":[{"name":"University of California at Davis Department of Pharmacology, , Davis, CA 95616 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meimi","family":"Zhao","sequence":"additional","affiliation":[{"name":"University of California at Davis Department of Pharmacology, , Davis, CA 95616 ,","place":["USA"]},{"name":"China Medical University Department of Pharmaceutical Toxicology, , Shenyang 110122 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luqi","family":"Zhao","sequence":"additional","affiliation":[{"name":"University of Houston Department of Pharmacological and Pharmaceutical Sciences, , Houston, TX 77204 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0155-2328","authenticated-orcid":false,"given":"Mingfu","family":"Wu","sequence":"additional","affiliation":[{"name":"University of Houston Department of Pharmacological and Pharmaceutical Sciences, , Houston, TX 77204 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1786-9143","authenticated-orcid":false,"given":"Yang K","family":"Xiang","sequence":"additional","affiliation":[{"name":"University of California at Davis Department of Pharmacology, , Davis, CA 95616 ,","place":["USA"]},{"name":"VA Northern California Health Care System , Mather, CA 95655 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","published-online":{"date-parts":[[2025,8,12]]},"reference":[{"key":"2025091915590490600_bib1","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1146\/annurev.physiol.70.113006.100455","article-title":"Calcium cycling and signaling in cardiac myocytes","volume":"70","author":"Bers","year":"2008","journal-title":"Annu Rev Physiol"},{"issue":"8","key":"2025091915590490600_bib2","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1161\/CIRCRESAHA.117.310355","article-title":"Calcium signaling and transcriptional regulation in cardiomyocytes","volume":"121","author":"Dewenter","year":"2017","journal-title":"Circ Res"},{"issue":"8","key":"2025091915590490600_bib3","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1006\/jmcc.2002.2038","article-title":"Calcium, calmodulin, and calcium-calmodulin kinase II: heartbeat to 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