{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T14:57:33Z","timestamp":1768748253029,"version":"3.49.0"},"reference-count":40,"publisher":"American Physiological Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2012,7,1]]},"abstract":"<jats:p>Transgenic mice with cardiac-specific expression of a peptide inhibitor of G protein-coupled receptor kinase (GRK)3 [transgenic COOH-terminal GRK3 (GRK3ct) mice] display myocardial hypercontractility without hypertrophy and enhanced \u03b1<jats:sub>1<\/jats:sub>-adrenergic receptor signaling. A role for GRK3 in the pathogenesis of heart failure (HF) has not been investigated, but inhibition of its isozyme, GRK2, has been beneficial in several HF models. Here, we tested whether inhibition of GRK3 modulated evolving cardiac hypertrophy and dysfunction after pressure overload. Weight-matched male GRK3ct transgenic and nontransgenic littermate control (NLC) mice subjected to chronic pressure overload by abdominal aortic banding (AB) were compared with sham-operated (SH) mice. At 6 wk after AB, a significant increase of cardiac mass consistent with induction of hypertrophy was found, but no differences between GRK3ct-AB and NLC-AB mice were discerned. Simultaneous left ventricular (LV) pressure-volume analysis of electrically paced, ex vivo perfused working hearts revealed substantially reduced systolic and diastolic function in NLC-AB mice ( n = 7), which was completely preserved in GRK3ct-AB mice ( n = 7). An additional cohort was subjected to in vivo cardiac catheterization and LV pressure-volume analysis at 12 wk after AB. NLC-AB mice ( n = 11) displayed elevated end-diastolic pressure (8.5 \u00b1 3.1 vs. 2.9 \u00b1 1.2 mmHg, P &lt; 0.05), reduced cardiac output (3,448 \u00b1 323 vs. 4,488 \u00b1 342 \u03bcl\/min, P &lt; 0.05), and reduced dP\/d t<jats:sub>max<\/jats:sub>and dP\/d t<jats:sub>min<\/jats:sub>(both P &lt; 0.05) compared with GRK3ct-AB mice ( n = 16), corroborating the preserved cardiac structure and function observed in GRK3ct-AB hearts assessed ex vivo. Increased cardiac mass and myocardial mRNA expression of \u03b2-myosin heavy chain confirmed the similar induction of cardiac hypertrophy in both AB groups, but only NLC-AB hearts displayed significantly elevated mRNA levels of brain natriuretic peptide and myocardial collagen contents as well as reduced \u03b2<jats:sub>1<\/jats:sub>-adrenergic receptor responsiveness to isoproterenol, indicating increased LV wall stress and the transition to HF. Inhibition of cardiac GRK3 in mice does not alter the hypertrophic response but attenuates cardiac dysfunction and HF after chronic pressure overload.<\/jats:p>","DOI":"10.1152\/ajpheart.00724.2011","type":"journal-article","created":{"date-parts":[[2012,4,29]],"date-time":"2012-04-29T00:16:20Z","timestamp":1335658580000},"page":"H66-H74","source":"Crossref","is-referenced-by-count":16,"title":["Cardiomyocyte-restricted inhibition of G protein-coupled receptor kinase-3 attenuates cardiac dysfunction after chronic pressure overload"],"prefix":"10.1152","volume":"303","author":[{"given":"Thomas G.","family":"von Lueder","sequence":"first","affiliation":[{"name":"Institute for Surgical Research, Oslo University Hospital, Rikshospitalet and University of Oslo, Oslo, Norway;"},{"name":"Department of Cardiology, Oslo University Hospital, Rikshospitalet and University of Oslo, Oslo, Norway;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00f8rgen","family":"Gravning","sequence":"additional","affiliation":[{"name":"Institute for Surgical Research, Oslo University Hospital, Rikshospitalet and University of Oslo, Oslo, Norway;"},{"name":"Department of Cardiology, Oslo University Hospital, Rikshospitalet and University of Oslo, Oslo, Norway;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ole-Jakob","family":"How","sequence":"additional","affiliation":[{"name":"Department of Medical Physiology, University of Troms\u00f8, Troms\u00f8, Norway; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leif E.","family":"Vinge","sequence":"additional","affiliation":[{"name":"Institute for Surgical Research, Oslo University Hospital, Rikshospitalet and University of Oslo, Oslo, Norway;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammed Shakil","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Institute for Surgical Research, Oslo University Hospital, Rikshospitalet and University of Oslo, Oslo, Norway;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kurt A.","family":"Krobert","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, University of Oslo and Oslo University Hospital, Oslo, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Finn Olav","family":"Levy","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, University of Oslo and Oslo University Hospital, Oslo, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Terje S.","family":"Larsen","sequence":"additional","affiliation":[{"name":"Department of Medical Physiology, University of Troms\u00f8, Troms\u00f8, Norway; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Otto 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