{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T12:23:54Z","timestamp":1783686234823,"version":"3.55.0"},"reference-count":54,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T00:00:00Z","timestamp":1783641600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Heart transplantation (HT) remains the definitive therapy for end-stage heart failure, yet rejection and cardiac allograft vasculopathy (CAV) continue to limit long-term outcomes. Beyond donor-specific HLA antibodies, non-HLA antibodies, particularly anti-angiotensin II type 1 receptor antibodies (AT1R-Abs), have been implicated in allograft injury, but published findings are heterogeneous. Aim: The aim of this study is to systematically evaluate the evidence linking AT1R gene expression and anti-AT1R antibodies with key post-heart transplant outcomes. Methods: We conducted a systematic review in accordance with PRISMA guidelines. Scopus, PubMed, Web of Science, and the Cochrane Library were searched (December 2025) for cohort and case\u2013control studies evaluating AT1R gene expression and\/or AT1R-Ab status in HT recipients and their association with post-transplant outcomes. Two reviewers independently screened studies, extracted data, and assessed risk of bias using the NIH Quality Assessment Tool. Results: Twelve studies encompassing 951 recipients met the inclusion criteria. Five studies evaluated AT1R mRNA expression, reporting variable patterns: several observed reduced AT1R\/AT2R transcription after transplantation without clear clinical correlation, whereas others associated higher donor or recipient AT1R expression with transplant coronary artery disease and recurrent rejection. AT1R-Ab prevalence varied widely and appeared to increase after mechanical circulatory support, with substantial seroconversion reported during LVAD support in initially antibody-negative patients. Associations between AT1R-Ab and acute cellular rejection and antibody-mediated rejection were inconsistent across studies, and survival findings were inconclusive; however, some reports linked elevated AT1R-Abs to poorer long-term freedom from adverse events. Evidence regarding CAV was mixed, with signals of increased vasculopathy risk in some cohorts but not others. Conclusions: Current evidence suggests a potential role for AT1R expression and AT1R-Abs in cardiac allograft dysfunction, including rejection phenotypes and vasculopathy. Larger prospective studies with harmonized testing strategies are needed to define clinically meaningful AT1R-Ab cutoffs and clarify their utility in risk stratification and targeted therapeutic trials.<\/jats:p>","DOI":"10.3390\/jcm15145419","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T11:43:34Z","timestamp":1783683814000},"page":"5419","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Angiotensin II Type 1 Receptor Expression and Anti-AT1R Antibodies in Heart Transplantation: A Systematic Review of Distinct but Related Non-HLA Immune Pathways"],"prefix":"10.3390","volume":"15","author":[{"given":"Radha","family":"Gopalan","sequence":"first","affiliation":[{"name":"Cardiology Department, Banner University Medical Center, Phoenix, AZ 85006, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2973-2913","authenticated-orcid":false,"given":"Mohamed Reyad","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Arizona College of Medicine-Phoenix, Phoenix, AZ 85004, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamal","family":"Mahar","sequence":"additional","affiliation":[{"name":"Cardiology Department, Banner University Medical Center, Phoenix, AZ 85006, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anusha","family":"Sunkara","sequence":"additional","affiliation":[{"name":"Cardiology Department, Banner University Medical Center, Phoenix, AZ 85006, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anantharam","family":"Kalya","sequence":"additional","affiliation":[{"name":"Cardiology Department, Banner University Medical Center, Phoenix, AZ 85006, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdelrahman","family":"Hafez","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Mayo Clinic, Phoenix, AZ 85054, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Reinsmoen","sequence":"additional","affiliation":[{"name":"HLA and Immunogenetics Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Arabia","sequence":"additional","affiliation":[{"name":"Cardiology Department, Banner University Medical Center, Phoenix, AZ 85006, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Moll, G., Dai, Z., and C\u00e2mara, N. 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