{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T19:47:49Z","timestamp":1790279269213,"version":"4.1.0"},"reference-count":55,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T00:00:00Z","timestamp":1739404800000},"content-version":"vor","delay-in-days":12,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["BHF- RG\/F\/22\/110081"],"award-info":[{"award-number":["BHF- RG\/F\/22\/110081"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,4,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>Caveolin-3 is essential for the formation of caveolae in cardiomyocytes. Caveolar microdomains have been shown to regulate the distribution of signalling proteins such as beta-adrenoceptors (\u03b2AR) and may act as membrane reserves to protect the cell from damage during the mechanical stretch. Myocardial stretch occurs during haemodynamic overload and may be normal (e.g. exercise) or pathological (e.g. heart failure); therefore, it is important to understand the effect of stretch on signalling pathways associated with mechanosensitive structures, such as caveolae. In this study, we investigate the role of caveolae in regulating the effect of stretch on \u03b2AR-signalling.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>We used osmotic swelling of isolated rat ventricular cardiomyocytes as a method to stretch the cell membrane and investigate the effect of \u03b2AR stimulation on cyclic adenosine monophosphate (cAMP) activity and contractility. \u03b2AR response was measured using a F\u00f6rster Resonance Energy Transfer reporter for the second messenger cAMP and using CytoCypher for the measurement of cell contractility. \u03b21AR and \u03b22AR blockers were used to selectively allow stimulation of \u03b22AR and \u03b21AR, respectively. We also investigated the effect of stretch on \u03b2AR response to isoprenaline stimulation in left ventricular trabeculae dissected from control and cardiac-specific caveolin-3 knock-out mice (Cav3KO). Stretching trabeculae produces increased baseline adenylyl cyclase activity and a higher level of cAMP and a greater \u03b22AR-induced positive inotropy after stimulation of the \u03b22AR but not \u03b21AR, by isoprenaline. Similar findings were confirmed for isolated myocytes subjected to hypoosmotic conditions. In isolated cardiomyocytes, caveolae depletion using methyl-beta-cyclodextrin or Cav3KO abolished the increase in \u03b22AR response induced by stretch.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Our study reveals a stretch-regulation of the \u03b22AR signalling pathway, which requires functional caveolae. This indicates caveolae are mechanosensitive membrane domains that undergo structural and functional changes in response to stretch, thus leading to mechanical regulation of caveolae-associated signalling pathways.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cvr\/cvae265","type":"journal-article","created":{"date-parts":[[2025,2,7]],"date-time":"2025-02-07T20:25:55Z","timestamp":1738959955000},"page":"440-453","source":"Crossref","is-referenced-by-count":8,"title":["Stretch regulation of \u03b22-Adrenoceptor signalling in cardiomyocytes requires caveolae"],"prefix":"10.1093","volume":"121","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4130-6746","authenticated-orcid":false,"given":"Jiarong","family":"Fu","sequence":"first","affiliation":[{"name":"National Heart and Lung Institute, Imperial College London , Du Cane Road, London W12 0NN 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