{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:13:51Z","timestamp":1760058831403,"version":"build-2065373602"},"reference-count":45,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T00:00:00Z","timestamp":1745798400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Comprehensive Heart Failure Center Wuerzburg"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>So far, the molecular functions of the angiotensin-type-2 receptor (AT2) interacting protein (ATIP1) have remained unclear, although expression studies have revealed high levels of ATIP1 in the heart. To unravel its physiological function, we investigated ATIP1-KO mice. They develop a spontaneous cardiac hypertrophy with a significantly increased heart\/bodyweight ratio, enlarged cardiomyocyte diameters, and augmented myocardial fibrosis. Hemodynamic measurements revealed an increased ejection fraction (EF) in untreated ATIP1-KO mice, and reduced end-systolic and end-diastolic volumes (ESV and EDV), which, in sum, reflect a compensated concentric cardiac hypertrophy. Importantly, no significant differences in blood pressure (BP) were observed. Chronic angiotensin II (AngII) infusion resulted in increases in BP and EF in ATIP1-KO and WT mice. Reductions in ESV and EDV occurred in both ATIP1-KO and WT but to a lesser extent in ATIP1-KOs. Isolated cardiomyocytes exhibited a significantly increased contractility in ATIP1-KO and accelerated Ca2+ decay. AngII treatment resulted in increased fractional shortening in WT but decreased shortening in ATIP1-KO, accompanied by accelerated cell relaxation in WT but absent effects on relaxation in ATIP1-KO cells. The AT2 agonist CGP42112A increased shortening in WT cardiomyocytes but, again, did not affect shortening in ATIP1-KO cells. Relaxation was accelerated by CGP42112A in WT but was unaffected in ATIP1-KO cells. We show that ATIP1 deficiency results in spontaneous cardiac hypertrophy in vivo and that ATIP1 is a downstream signal in the AT2 pathway regulating cell contractility. We hypothesize that the latter effect is because of a disinhibition of the AT1 pathway by impaired AT2 signaling.<\/jats:p>","DOI":"10.3390\/cells14090645","type":"journal-article","created":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T11:35:13Z","timestamp":1746185713000},"page":"645","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["ATIP1 Is a Suppressor of Cardiac Hypertrophy and Modulates AT2-Dependent Signaling in Cardiac Myocytes"],"prefix":"10.3390","volume":"14","author":[{"given":"Tobias","family":"Fischer","sequence":"first","affiliation":[{"name":"Institute of Physiology I, University of Wuerzburg, 97070 Wuerzburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sina","family":"Gredy","sequence":"additional","affiliation":[{"name":"Institute of Physiology I, University of Wuerzburg, 97070 Wuerzburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadine","family":"Scheel","sequence":"additional","affiliation":[{"name":"Institute of Physiology I, University of Wuerzburg, 97070 Wuerzburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter M.","family":"Benz","sequence":"additional","affiliation":[{"name":"Institute of Physiology I, University of Wuerzburg, 97070 Wuerzburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin","family":"Fissler","sequence":"additional","affiliation":[{"name":"Institute of Physiology I, University of Wuerzburg, 97070 Wuerzburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melanie","family":"Ullrich","sequence":"additional","affiliation":[{"name":"Institute of Physiology I, University of Wuerzburg, 97070 Wuerzburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Abe\u00dfer","sequence":"additional","affiliation":[{"name":"Institute of Physiology I, University of Wuerzburg, 97070 Wuerzburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam G.","family":"Rokita","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Pneumology, Georg-August-University, 37075 Goettingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jochen","family":"Reichle","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Pneumology, Georg-August-University, 37075 Goettingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9915-4429","authenticated-orcid":false,"given":"Lars S.","family":"Maier","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, University Clinic Regensburg, 93053 Regensburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oliver","family":"Ritter","sequence":"additional","affiliation":[{"name":"Brandenburg University Hospital, Department of Internal Medicine I, 14770 Brandenburg an der Havel, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hideo A.","family":"Baba","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University of Duisburg\u2013Essen, 45147 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4475-0412","authenticated-orcid":false,"given":"Kai","family":"Schuh","sequence":"additional","affiliation":[{"name":"Institute of Physiology I, University of Wuerzburg, 97070 Wuerzburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/S0031-6997(24)01458-3","article-title":"International union of pharmacology. 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