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Healthy mongrel canines were implanted with pacemakers to deliver bigeminal PVCs (50% burden with 200\u2013220\u2009ms coupling interval). After 12\u2009weeks, left ventricular (LV) free wall samples were studied from PVC\u2010CM and Sham groups. In addition to reduced LV ejection fraction (LVEF), the PVC\u2010CM group showed larger cardiac myocytes without evident ultrastructural alterations compared to the Sham group. Biochemical markers of pathological hypertrophy, such as store\u2010operated Ca<jats:sup>2+<\/jats:sup> entry, calcineurin\/NFAT pathway, \u03b2\u2010myosin heavy chain, and skeletal type \u03b1\u2010actin were unaltered in the PVC\u2010CM group. In contrast, pro\u2010hypertrophic and antiapoptotic pathways including ERK1\/2 and AKT\/mTOR were activated and\/or overexpressed in the PVC\u2010CM group, which appeared counterbalanced by an overexpression of protein phosphatase 1 and a borderline elevation of the anti\u2010hypertrophic factor atrial natriuretic peptide. Moreover, the potent angiogenic and pro\u2010hypertrophic factor VEGF\u2010A and its receptor VEGFR2 were significantly elevated in the PVC\u2010CM group. In conclusion, a molecular program is in place to keep this structural remodeling associated with frequent PVCs as an adaptive pathological hypertrophy.<\/jats:p>","DOI":"10.1002\/iub.2765","type":"journal-article","created":{"date-parts":[[2023,7,10]],"date-time":"2023-07-10T12:55:12Z","timestamp":1688993712000},"page":"926-940","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Mechanisms of adaptive hypertrophic cardiac remodeling in a large animal model of premature ventricular contraction\u2010induced cardiomyopathy"],"prefix":"10.1002","volume":"75","author":[{"given":"Jaime","family":"Balderas\u2010Villalobos","sequence":"first","affiliation":[{"name":"Department of Physiology and Biophysics, School of Medicine Virginia Commonwealth University  Richmond Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. M. 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