{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T16:33:42Z","timestamp":1758818022868,"version":"3.41.2"},"reference-count":35,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2019,4,16]]},"abstract":"\n Background<\/jats:title>\n \n We have previously shown that ATRAP (angiotensin\n II<\/jats:styled-content>\n receptor\u2013associated protein;\n Agtrap<\/jats:italic>\n ) interacts with AT1R (angiotensin\n II<\/jats:styled-content>\n type 1 receptor) and promotes constitutive internalization of\n AT<\/jats:styled-content>\n 1R so as to inhibit hyperactivation of its downstream signaling. In response to angiotensin\n II<\/jats:styled-content>\n , systemic\n ATRAP<\/jats:styled-content>\n deficiency exacerbates angiotensin\n II<\/jats:styled-content>\n \u2013mediated hypertension via hyperactivation of renal tubular\n AT<\/jats:styled-content>\n 1R. Although\n ATRAP<\/jats:styled-content>\n expression is abundant in renal proximal tubules, little is known about the actual function of renal proximal tubule\n ATRAP<\/jats:styled-content>\n in angiotensin\u2010mediated hypertension.\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n In this study, we examined the in\u00a0vivo functional role of renal proximal tubule\n ATRAP<\/jats:styled-content>\n in angiotensin\u2010dependent hypertension. We succeeded in generating proximal tubule\u2013specific\n ATRAP<\/jats:styled-content>\n knockout (\n PT<\/jats:styled-content>\n \u2010\n KO<\/jats:styled-content>\n ) mice for the first time using the Cre\/loxP system with\n Pepck<\/jats:italic>\n \u2010Cre. Detailed analysis of renal\n ATRAP<\/jats:styled-content>\n expression in\n PT<\/jats:styled-content>\n \u2010\n KO<\/jats:styled-content>\n mice estimated by immunohistochemical and laser\u2010capture microdissection analysis revealed that\n ATRAP mRNA<\/jats:styled-content>\n expression decreased by \u224880% in proximal regions of the nephron in\n PT<\/jats:styled-content>\n \u2010\n KO<\/jats:styled-content>\n mice compared with wild\u2010type (\n WT<\/jats:styled-content>\n ) mice. We compared blood pressure of\n PT<\/jats:styled-content>\n \u2010\n KO<\/jats:styled-content>\n and\n WT<\/jats:styled-content>\n mice using both tail\u2010cuff and radiotelemetric methods. Blood pressure of\n PT<\/jats:styled-content>\n \u2010\n KO<\/jats:styled-content>\n mice was comparable with that of\n WT<\/jats:styled-content>\n mice at baseline. Moreover, no significant differences were noted in pressor response to angiotensin\n II<\/jats:styled-content>\n (600\u00a0ng\/kg per min or 1000\u00a0ng\/kg per minute) infusion between\n PT<\/jats:styled-content>\n \u2010\n KO<\/jats:styled-content>\n and\n WT<\/jats:styled-content>\n mice. In addition, angiotensin\n II<\/jats:styled-content>\n \u2013mediated cardiac hypertrophy was identical between\n PT<\/jats:styled-content>\n \u2010\n KO<\/jats:styled-content>\n and\n WT<\/jats:styled-content>\n mice.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n ATRAP<\/jats:styled-content>\n deficiency in proximal tubules did not exacerbate angiotensin\u2010dependent hypertension in\u00a0vivo. The results indicate that renal proximal tubule\n ATRAP<\/jats:styled-content>\n has a minor role in angiotensin\u2010dependent hypertension in\u00a0vivo.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.119.012395","type":"journal-article","created":{"date-parts":[[2019,4,12]],"date-time":"2019-04-12T09:08:18Z","timestamp":1555060098000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":10,"title":["Effects of ATRAP in Renal Proximal Tubules on Angiotensin\u2010Dependent Hypertension"],"prefix":"10.1161","volume":"8","author":[{"given":"Sho","family":"Kinguchi","sequence":"first","affiliation":[{"name":"Department of Medical Science and Cardiorenal Medicine Yokohama City University Graduate School of Medicine Yokohama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiromichi","family":"Wakui","sequence":"additional","affiliation":[{"name":"Department of Medical Science and Cardiorenal Medicine Yokohama 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