{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T16:43:08Z","timestamp":1791304988659,"version":"4.3.1"},"reference-count":37,"publisher":"National Academy of Sciences","issue":"4","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2014,1,28]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>Cardiac hypertrophy and dysfunction in response to sustained hormonal and mechanical stress are sentinel features of most forms of heart disease. Activation of non\u2013voltage-gated transient receptor potential canonical channels TRPC3 and TRPC6 may contribute to this pathophysiology and provide a therapeutic target. Effects from combined selective inhibition have not been tested previously. Here we report the capability of highly selective TRPC3\/6 inhibitors to block pathological hypertrophic signaling in several cell types, including adult cardiac myocytes. We show in vivo redundancy of each channel; individual gene deletion was not protective against sustained pressure overload, whereas combined deletion ameliorated the response. These data strongly support a role for both channels in cardiac disease and the utility of selective combined inhibition.<\/jats:p>","DOI":"10.1073\/pnas.1308963111","type":"journal-article","created":{"date-parts":[[2014,1,22]],"date-time":"2014-01-22T22:42:30Z","timestamp":1390430550000},"page":"1551-1556","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":194,"title":["Combined TRPC3 and TRPC6 blockade by selective small-molecule or genetic deletion inhibits pathological cardiac hypertrophy"],"prefix":"10.1073","volume":"111","author":[{"given":"Kinya","family":"Seo","sequence":"first","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD 21205;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter P.","family":"Rainer","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD 21205;"},{"name":"Division of Cardiology, Department of Medicine, Medical University of Graz, 8036 Graz, Austria;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginia","family":"Shalkey Hahn","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD 21205;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong-ik","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD 21205;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su-Hyun","family":"Jo","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD 21205;"},{"name":"Department of Physiology, Institute of Bioscience and Biotechnology, Kangwon National University School of Medicine, Chuncheon 200-701, South Korea;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asger","family":"Andersen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Aarhus University Hospital, 8200 Aarhus, Denmark;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD 21205;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoping","family":"Xu","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline Heart Failure Discovery Performance Unit, King of Prussia, PA 19406; 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