{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T22:24:25Z","timestamp":1792794265399,"version":"4.5.0"},"reference-count":47,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,12,18]],"date-time":"2017-12-18T00:00:00Z","timestamp":1513555200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004411","name":"Heart and Stroke Foundation of Canada","doi-asserted-by":"publisher","award":["G\u201015\u20100009078"],"award-info":[{"award-number":["G\u201015\u20100009078"]}],"id":[{"id":"10.13039\/100004411","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmacology Res &amp; Perspec"],"published-print":{"date-parts":[[2018,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hypertension is associated with vascular remodeling due to hyperproliferation and hypertrophy of vascular smooth muscle cells (VSMC). Recently, we showed the implication of enhanced expression of Gq\u03b1 and PLC\u03b21 proteins in hypertrophy of VSMCs from 16\u2010week\u2010old spontaneously hypertensive rats (SHR). The aim of this study was to investigate whether C\u2010ANP<jats:sub>4\u201023<\/jats:sub>, a natriuretic peptide receptor\u2010C (NPR\u2010C) ligand that was shown to inhibit vasoactive peptide\u2010induced enhanced protein synthesis in A10 VSMC could also attenuate hypertrophy of VSMC isolated from rat model of cardiac hypertrophy and to further explore the possible involvement of Gq\u03b1\/PLC\u03b21 proteins and ROS\u2010mediated signaling in this effect. The protein synthesis and cell volume, markers of hypertrophy were significantly enhanced in VSMC from 16\u2010week\u2010old SHR compared with age\u2010matched WKY rats and C\u2010ANP<jats:sub>4\u201023<\/jats:sub>treatment attenuated both to WKY levels. In addition, C\u2010ANP<jats:sub>4\u201023<\/jats:sub>treatment also attenuated the enhanced expression of AT1 receptor, Gq\u03b1, PLC\u03b21, Nox4, and p47<jats:sup>phox<\/jats:sup>proteins, the enhanced activation of EGFR, PDGFR, IGF\u20101R, enhanced phosphorylation of ERK1\/2\/AKT and c\u2010Src in VSMC from SHR. Furthermore, the enhanced levels of superoxide anion and NADPH oxidase activity exhibited by VSMC from SHR were also attenuated to control levels by C\u2010ANP<jats:sub>4\u201023<\/jats:sub>treatment. These results indicate that C\u2010ANP<jats:sub>4\u201023<\/jats:sub>via the activation of NPR\u2010C attenuates VSMC hypertrophy through decreasing the overexpression of Gq\u03b1\/PLC\u03b21 proteins, enhanced oxidative stress, increased activation of growth factor receptors, and enhanced phosphorylation of MAPK\/AKT signaling pathways. Thus, it can be suggested that C\u2010ANP<jats:sub>4\u201023<\/jats:sub>may be used as a therapeutic agent for the treatment of vascular complications associated with hypertension and atherosclerosis.<\/jats:p>","DOI":"10.1002\/prp2.375","type":"journal-article","created":{"date-parts":[[2017,12,23]],"date-time":"2017-12-23T02:03:36Z","timestamp":1513994616000},"source":"Crossref","is-referenced-by-count":16,"title":["Natriuretic peptide receptor\u2010C\u2010mediated attenuation of vascular smooth muscle cell hypertrophy involves Gq\u03b1\/PLC\u03b21 proteins and ROS\u2010associated signaling"],"prefix":"10.1002","volume":"6","author":[{"given":"Ashish","family":"Jain","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Physiology Faculty of Medicine University of Montreal Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9419-064X","authenticated-orcid":false,"given":"Madhu B.","family":"Anand\u2010Srivastava","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology Faculty of Medicine University of Montreal Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,12,18]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1590\/S0100-879X2002000900001"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2005.08.004"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1987.tb29479.x"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1846707"},{"key":"e_1_2_9_6_1","doi-asserted-by":"crossref","first-page":"3569","DOI":"10.1210\/en.2007-1694","article-title":"Central role of Gq in the hypertrophic signal transduction of angiotensin II in vascular smooth muscle cells","volume":"149","author":"Ohtsu H","year":"2008","journal-title":"Endocrinology"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00337.2013"},{"key":"e_1_2_9_8_1","first-page":"02015","article-title":"Oxidative stress contributes to the enhanced expression of Gqalpha\/PLCbeta1 proteins and hypertrophy of VSMC from SHR: role of growth factor receptor transactivation","volume":"00659","author":"Atef ME","year":"2016","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0157955"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1990.70.3.665"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/332078a0"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/338078a0"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/341068a0"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(89)90513-8"},{"key":"e_1_2_9_15_1","doi-asserted-by":"crossref","first-page":"4931","DOI":"10.1016\/S0021-9258(18)61132-9","article-title":"Pertussis toxin attenuates atrial natriuretic factor\u2010mediated inhibition of adenylate cyclase. Involvement of inhibitory guanine nucleotide regulatory protein","volume":"262","author":"Anand\u2010Srivastava MB","year":"1987","journal-title":"J Biol Chem"},{"key":"e_1_2_9_16_1","doi-asserted-by":"crossref","first-page":"8566","DOI":"10.1016\/S0021-9258(19)38925-2","article-title":"Ring\u2010deleted analogs of atrial natriuretic factor inhibit adenylate cyclase\/cAMP system. Possible coupling of clearance atrial natriuretic factor receptors to adenylate cyclase\/cAMP signal transduction system","volume":"265","author":"Anand\u2010Srivastava MB","year":"1990","journal-title":"J Biol Chem"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/0167-4889(89)90060-8"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.35.1.19"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.051625598"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.26.14730"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2006.08.012"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(82)91853-8"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2011.06.006"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0179301"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0076183"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.hjh.0000191905.26853.f1"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.34.21253"},{"issue":"1","key":"e_1_2_9_28_1","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1042\/bj3140115","article-title":"Adrenergic receptor stimulation of the mitogen\u2010activated protein kinase cascade and cardiac hypertrophy","volume":"314","author":"Bogoyevitch MA","year":"1996","journal-title":"Biochem J"},{"key":"e_1_2_9_29_1","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/S0026-895X(24)23199-0","article-title":"Mechanisms of impaired beta\u2010adrenergic receptor signaling in G(alphaq)\u2010mediated cardiac hypertrophy and ventricular dysfunction","volume":"57","author":"Dorn GW","year":"2000","journal-title":"Mol Pharmacol"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.12.6391"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.21.10109"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1003553107"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0706711"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00880.2007"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00269.2012"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.107.101253"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2010.10.005"},{"key":"e_1_2_9_38_1","first-page":"3264","article-title":"Oxidative stress and cardiovascular disease","volume":"96","author":"Griendling KK","year":"1997","journal-title":"Circulation"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.22.4.523"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.prostaglandins.2007.10.009"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00638.2004"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.113.01772"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.fjc.0000166220.65593.22"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2013.10.002"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1139\/Y09-056"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00526.2010"},{"key":"e_1_2_9_47_1","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1016\/j.freeradbiomed.2010.07.023","article-title":"Role of oxidative stress in high\u2010glucose\u2010 and diabetes\u2010induced increased expression of Gq\/11alpha proteins and associated signaling in vascular smooth muscle cells","volume":"49","author":"Descorbeth M","year":"2010","journal-title":"Free Radic Biol Med"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.062453699"}],"container-title":["Pharmacology Research &amp; Perspectives"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fprp2.375","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/prp2.375","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,29]],"date-time":"2025-06-29T04:31:43Z","timestamp":1751171503000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1002\/prp2.375"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,12,18]]},"references-count":47,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2018,2]]}},"alternative-id":["10.1002\/prp2.375"],"URL":"https:\/\/doi.org\/10.1002\/prp2.375","archive":["Portico"],"relation":{},"ISSN":["2052-1707","2052-1707"],"issn-type":[{"value":"2052-1707","type":"print"},{"value":"2052-1707","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,12,18]]},"article-number":"e00375"}}