{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T03:38:52Z","timestamp":1790912332955,"version":"4.1.0"},"reference-count":59,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"24","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2015,6,16]]},"abstract":"<jats:sec>\n            <jats:title>Background\u2014<\/jats:title>\n            <jats:p>L-type calcium channel activity is critical to afterload-induced hypertrophic growth of the heart. However, the mechanisms governing mechanical stress\u2013induced activation of L-type calcium channel activity are obscure. Polycystin-1 (PC-1) is a G protein\u2013coupled receptor\u2013like protein that functions as a mechanosensor in a variety of cell types and is present in cardiomyocytes.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results\u2014<\/jats:title>\n            <jats:p>We subjected neonatal rat ventricular myocytes to mechanical stretch by exposing them to hypo-osmotic medium or cyclic mechanical stretch, triggering cell growth in a manner dependent on L-type calcium channel activity. RNAi-dependent knockdown of PC-1 blocked this hypertrophy. Overexpression of a C-terminal fragment of PC-1 was sufficient to trigger neonatal rat ventricular myocyte hypertrophy. Exposing neonatal rat ventricular myocytes to hypo-osmotic medium resulted in an increase in \u03b11C protein levels, a response that was prevented by PC-1 knockdown. MG132, a proteasomal inhibitor, rescued PC-1 knockdown\u2013dependent declines in \u03b11C protein. To test this in vivo, we engineered mice harboring conditional silencing of PC-1 selectively in cardiomyocytes (PC-1 knockout) and subjected them to mechanical stress in vivo (transverse aortic constriction). At baseline, PC-1 knockout mice manifested decreased cardiac function relative to littermate controls, and \u03b11C L-type calcium channel protein levels were significantly lower in PC-1 knockout hearts. Whereas control mice manifested robust transverse aortic constriction\u2013induced increases in cardiac mass, PC-1 knockout mice showed no significant growth. Likewise, transverse aortic constriction\u2013elicited increases in hypertrophic markers and interstitial fibrosis were blunted in the knockout animals<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion\u2014<\/jats:title>\n            <jats:p>PC-1 is a cardiomyocyte mechanosensor that is required for cardiac hypertrophy through a mechanism that involves stabilization of \u03b11C protein.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circulationaha.114.013537","type":"journal-article","created":{"date-parts":[[2015,4,18]],"date-time":"2015-04-18T01:52:42Z","timestamp":1429321962000},"page":"2131-2142","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":80,"title":["Polycystin-1 Is a Cardiomyocyte Mechanosensor That Governs L-Type Ca\n            <sup>2+<\/sup>\n            Channel Protein Stability"],"prefix":"10.1161","volume":"131","author":[{"given":"Zully","family":"Pedrozo","sequence":"first","affiliation":[{"name":"From Division of Cardiology, Department of Internal Medicine (Z.P., A.C., P.K.B., C.R.M., N.J., X.L., B.A.R., T.G.G., S.L., J.A.H.) and Department of Molecular Biology (B.A.R., J.A.H.), UT Southwestern Medical Center, Dallas, TX; Advanced Center for Chronic Diseases and Centro de Estudios Moleculares de la C\u00e9lula, Facultad de Medicina &amp; Facultad de Ciencias Qu\u00edmicas y Farmac\u00e9uticas, Santiago, Chile (Z.P., A.C.-F., C.F., S.L.); Instituto de Ciencias Biom\u00e9dicas, Facultad de Medicina (Z.P., S.L.)..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfredo","family":"Criollo","sequence":"additional","affiliation":[{"name":"From Division of Cardiology, Department of Internal Medicine (Z.P., A.C., P.K.B., C.R.M., N.J., X.L., B.A.R., T.G.G., S.L., J.A.H.) and Department of Molecular Biology (B.A.R., J.A.H.), UT Southwestern Medical Center, Dallas, TX; Advanced Center for Chronic Diseases and Centro de Estudios Moleculares de la C\u00e9lula, Facultad de Medicina &amp; Facultad de Ciencias Qu\u00edmicas y Farmac\u00e9uticas, Santiago, Chile (Z.P., A.C.-F., C.F., S.L.); Instituto de Ciencias Biom\u00e9dicas, Facultad de Medicina (Z.P., S.L.)..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavan K.","family":"Battiprolu","sequence":"additional","affiliation":[{"name":"From Division of Cardiology, Department of Internal Medicine (Z.P., A.C., P.K.B., C.R.M., N.J., X.L., B.A.R., T.G.G., S.L., J.A.H.) and Department of Molecular Biology (B.A.R., J.A.H.), UT Southwestern Medical Center, Dallas, TX; Advanced Center for Chronic Diseases and Centro de Estudios Moleculares de la C\u00e9lula, Facultad de Medicina &amp; Facultad de Ciencias Qu\u00edmicas y Farmac\u00e9uticas, Santiago, Chile (Z.P., A.C.-F., C.F., S.L.); Instituto de Ciencias Biom\u00e9dicas, Facultad de Medicina (Z.P., S.L.)..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cyndi R.","family":"Morales","sequence":"additional","affiliation":[{"name":"From Division of Cardiology, Department of Internal Medicine (Z.P., A.C., P.K.B., C.R.M., N.J., X.L., B.A.R., T.G.G., S.L., J.A.H.) and Department of Molecular Biology (B.A.R., J.A.H.), UT Southwestern Medical Center, Dallas, TX; Advanced Center for Chronic Diseases and Centro de Estudios Moleculares de la C\u00e9lula, Facultad de Medicina &amp; Facultad de Ciencias Qu\u00edmicas y Farmac\u00e9uticas, Santiago, Chile (Z.P., A.C.-F., C.F., S.L.); Instituto de Ciencias Biom\u00e9dicas, Facultad de Medicina (Z.P., S.L.)..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariel","family":"Contreras-Ferrat","sequence":"additional","affiliation":[{"name":"From Division of Cardiology, Department of Internal Medicine (Z.P., A.C., P.K.B., C.R.M., N.J., X.L., B.A.R., T.G.G., S.L., J.A.H.) and Department of Molecular Biology (B.A.R., J.A.H.), UT Southwestern Medical Center, Dallas, TX; Advanced Center for Chronic Diseases and Centro de Estudios Moleculares de la C\u00e9lula, Facultad de Medicina &amp; Facultad de Ciencias Qu\u00edmicas y Farmac\u00e9uticas, Santiago, Chile (Z.P., A.C.-F., C.F., S.L.); Instituto de Ciencias Biom\u00e9dicas, Facultad de Medicina (Z.P., S.L.)..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"From Division of Cardiology, Department of Internal Medicine (Z.P., A.C., P.K.B., C.R.M., N.J., X.L., B.A.R., T.G.G., S.L., J.A.H.) and Department of Molecular Biology (B.A.R., J.A.H.), UT Southwestern Medical Center, Dallas, TX; Advanced Center for Chronic Diseases and Centro de Estudios Moleculares de la C\u00e9lula, Facultad de Medicina &amp; Facultad de Ciencias Qu\u00edmicas y Farmac\u00e9uticas, Santiago, Chile (Z.P., A.C.-F., C.F., S.L.); Instituto de Ciencias Biom\u00e9dicas, Facultad de Medicina (Z.P., S.L.)..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Jiang","sequence":"additional","affiliation":[{"name":"From Division of Cardiology, Department of Internal Medicine (Z.P., A.C., P.K.B., C.R.M., N.J., X.L., B.A.R., T.G.G., S.L., J.A.H.) and Department of Molecular Biology (B.A.R., J.A.H.), UT Southwestern Medical Center, Dallas, TX; Advanced Center for Chronic Diseases and Centro de Estudios Moleculares de la C\u00e9lula, Facultad de Medicina &amp; Facultad de Ciencias Qu\u00edmicas y Farmac\u00e9uticas, Santiago, Chile (Z.P., A.C.-F., C.F., S.L.); Instituto de Ciencias Biom\u00e9dicas, Facultad de Medicina (Z.P., S.L.)..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Luo","sequence":"additional","affiliation":[{"name":"From Division of Cardiology, Department of Internal Medicine (Z.P., A.C., P.K.B., C.R.M., N.J., X.L., B.A.R., T.G.G., S.L., J.A.H.) and Department of Molecular Biology (B.A.R., J.A.H.), UT Southwestern Medical Center, Dallas, TX; Advanced Center for Chronic Diseases and Centro de Estudios Moleculares de la C\u00e9lula, Facultad de Medicina &amp; Facultad de Ciencias Qu\u00edmicas y Farmac\u00e9uticas, Santiago, Chile (Z.P., A.C.-F., C.F., S.L.); Instituto de Ciencias Biom\u00e9dicas, Facultad de Medicina (Z.P., S.L.)..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Caplan","sequence":"additional","affiliation":[{"name":"From Division of Cardiology, Department of Internal Medicine (Z.P., A.C., P.K.B., C.R.M., N.J., X.L., B.A.R., T.G.G., S.L., J.A.H.) and Department of Molecular Biology (B.A.R., J.A.H.), UT Southwestern Medical Center, Dallas, TX; Advanced Center for Chronic Diseases and Centro de Estudios Moleculares de la C\u00e9lula, Facultad de Medicina &amp; Facultad de Ciencias Qu\u00edmicas y Farmac\u00e9uticas, Santiago, Chile (Z.P., A.C.-F., C.F., S.L.); Instituto de Ciencias Biom\u00e9dicas, Facultad de Medicina (Z.P., S.L.)..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Somlo","sequence":"additional","affiliation":[{"name":"From Division of Cardiology, Department of Internal Medicine (Z.P., A.C., P.K.B., C.R.M., N.J., X.L., B.A.R., T.G.G., S.L., J.A.H.) and Department of Molecular Biology (B.A.R., J.A.H.), UT Southwestern Medical Center, Dallas, TX; Advanced Center for Chronic Diseases and Centro de Estudios Moleculares de la C\u00e9lula, Facultad de Medicina &amp; Facultad de Ciencias Qu\u00edmicas y Farmac\u00e9uticas, Santiago, Chile (Z.P., A.C.-F., C.F., S.L.); Instituto de Ciencias Biom\u00e9dicas, Facultad de Medicina (Z.P., S.L.)..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beverly A.","family":"Rothermel","sequence":"additional","affiliation":[{"name":"From Division of Cardiology, Department of Internal Medicine (Z.P., A.C., P.K.B., C.R.M., N.J., X.L., B.A.R., T.G.G., S.L., J.A.H.) and Department of Molecular Biology (B.A.R., J.A.H.), UT Southwestern Medical Center, Dallas, TX; Advanced Center for Chronic Diseases and Centro de Estudios Moleculares de la C\u00e9lula, Facultad de Medicina &amp; Facultad de Ciencias Qu\u00edmicas y Farmac\u00e9uticas, Santiago, Chile (Z.P., A.C.-F., C.F., S.L.); Instituto de Ciencias Biom\u00e9dicas, Facultad de Medicina (Z.P., S.L.)..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas G.","family":"Gillette","sequence":"additional","affiliation":[{"name":"From Division of Cardiology, Department of Internal Medicine (Z.P., A.C., P.K.B., C.R.M., N.J., X.L., B.A.R., T.G.G., S.L., J.A.H.) and Department of Molecular Biology (B.A.R., J.A.H.), UT Southwestern Medical Center, Dallas, TX; Advanced Center for Chronic Diseases and Centro de Estudios Moleculares de la C\u00e9lula, Facultad de Medicina &amp; Facultad de Ciencias Qu\u00edmicas y Farmac\u00e9uticas, Santiago, Chile (Z.P., A.C.-F., C.F., S.L.); Instituto de Ciencias Biom\u00e9dicas, Facultad de Medicina (Z.P., S.L.)..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Lavandero","sequence":"additional","affiliation":[{"name":"From Division of Cardiology, Department of Internal Medicine (Z.P., A.C., P.K.B., C.R.M., N.J., X.L., B.A.R., T.G.G., S.L., J.A.H.) and Department of Molecular Biology (B.A.R., J.A.H.), UT Southwestern Medical Center, Dallas, TX; Advanced Center for Chronic Diseases and Centro de Estudios Moleculares de la C\u00e9lula, Facultad de Medicina &amp; Facultad de Ciencias Qu\u00edmicas y Farmac\u00e9uticas, Santiago, Chile (Z.P., A.C.-F., C.F., S.L.); Instituto de Ciencias Biom\u00e9dicas, Facultad de Medicina (Z.P., S.L.)..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph A.","family":"Hill","sequence":"additional","affiliation":[{"name":"From Division of Cardiology, Department of Internal Medicine (Z.P., A.C., P.K.B., C.R.M., N.J., X.L., B.A.R., T.G.G., S.L., J.A.H.) and Department of Molecular Biology (B.A.R., J.A.H.), UT Southwestern Medical Center, Dallas, TX; Advanced Center for Chronic Diseases and Centro de Estudios Moleculares de la C\u00e9lula, Facultad de Medicina &amp; Facultad de Ciencias Qu\u00edmicas y Farmac\u00e9uticas, Santiago, Chile (Z.P., A.C.-F., C.F., S.L.); Instituto de Ciencias Biom\u00e9dicas, Facultad de Medicina (Z.P., S.L.)..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","first-page":"1:Chap. 14","volume-title":"In: Muscle Fundamental Biology and Mechanisms of Disease","author":"Dobner S","year":"2012","unstructured":"Dobner S, Amadi OC, Lee RT. 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