Antibody-mediated mechanisms directed against non-HLA related targets may exert negative impact on allograft function and survival. Angiotensin type 1 receptor (AT(1)R) emerges as a functional target for non-HLA allo- and autoantibodies (AT(1)R-Abs) comprising of IgG1 and IgG3 subclasses. Proof of concept for pathophysiologic relevance of AT(1)R-Abs in antibody mediated rejection (AMR) in renal transplants was provided by passive transfer studies in animal model and therapeutic rescue of patients. Although AT(1)R-Abs may belong to complement fixing IgG subclasses, C4d positivity in renal transplant biopsies was not frequently detected implicating complement independent mechanisms of injury. AT(1)R-Abs exert direct effects on endothelial and vascular smooth muscle cells by induction of Erk1/2 signaling and increased DNA binding of transcription factors associated with pro-inflammatory and pro-coagulatory responses. Establishment of enzyme-linked immunosorbent assay employing extracts of cells overexpressing AT(1)R in its native conformation was instrumental for recent studies in independent cohorts. Assessing the AT(1)R-Ab-status along with the HLA-antibodies may help to identify patients at particular risk for irreversible acute or chronic allograft injuries and improve overall outcomes. This review summarizes the current state of research in AT(1)R biology, development in diagnostic strategies, discusses recent clinical studies, and provides perspectives on further refinements in understanding AT(1)R-Ab-actions.
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http://dx.doi.org/10.1016/j.humimm.2012.07.010 | DOI Listing |
Diabetes
January 2025
Centre de recherche, Centre hospitalier de l'Université de Montréal (CRCHUM) and Département de médecine, Université de Montréal, 900 Saint Denis Street, Montréal, QC Canada H2X 0A9.
The role of the intrarenal renin-angiotensin system (iRAS) in diabetic kidney disease (DKD) progression remains unclear. In this study, we generated mice with renal tubule-specific deletion of angiotensinogen (Agt; RT-Agt-/-) in both Akita and streptozotocin (STZ)-induced mouse model of diabetes. Both Akita RT-Agt-/- and STZ-RT-Agt-/- mice exhibited significant attenuation of glomerular hyperfiltration, urinary albumin/creatinine ratio, glomerulomegaly and tubular injury.
View Article and Find Full Text PDFBMC Pregnancy Childbirth
January 2025
Collection Biologique de L'Hôpital de La Mère Et de L'Enfant CB-HME (Mother and Child Biobank), University Hospital Center, 8 Avenue Dominique Larrey, Limoges, France.
Background: Maternal agonistic autoantibodies against the angiotensin II type 1 receptor (AT1-AAs) have been implicated in the pathophysiology of preeclampsia, but their presence in their offsprings and their possible neonatal effects have not been specifically explored. This prospective study aimed to evaluate the presence of AT1-AAs and their potential clinical effects in neonates of AT1-AAs positive mothers.
Methods: Women with preeclampsia and their neonates were included.
Avian Pathol
January 2025
Department of Animal Husbandry, Autonomous University of Chapingo, Chapingo, State of Mexico 56230, Mexico.
Ascites syndrome (AS) is a deadly condition in fast-growing chickens, preceded by pulmonary arterial hypertension (PAH), where the angiotensin II type 1 receptor (ATR1) plays a role. We investigated whether allicin (ALLI), a garlic derivative, could (a) interact with broiler ATR1, (b) affect ascites-related traits [haematocrit content (Hct%), blood oxygen saturation (SaO), and the right-to-total ventricular weight ratio (RV:TV)], (c) modify ATR1 expression in the lung, heart, and liver, alongside ascites mortality and growth performance in Ross 308 broilers raised at high altitude and under cold temperatures promoting PAH/AS. Three groups (n = 70 each) were studied: 0-ALLI (untreated), 1-ALLI (allicin 1 mg/kg body weight/daily at 14-27 days of age by oral-oesophageal route), and 2.
View Article and Find Full Text PDFRegul Toxicol Pharmacol
December 2024
Division of Nephrology, University of Utah Health, Salt Lake City, UT, USA.
Marketed endothelin receptor antagonists (ERAs) have been associated with testicular tubular atrophy and decreases in male animal fertility in chronic toxicity studies in rats and dogs. Consistent with these findings, reduced sperm count has been observed in the clinical setting and is considered a potential class risk with chronic administration of ERAs. In contrast, no such effects on male animal fertility are noted with angiotensin II type 1 receptor blocker (ARB) treatment.
View Article and Find Full Text PDFCardiovasc Ther
January 2025
Department of Cardiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Heart failure (HF) and renal dysfunction often coexist and interact in many complex and bidirectional pathways, leading to detrimental effects on patient outcomes. The treatment of HF patients with renal dysfunction presents a significant clinical challenge. Interestingly, sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor (ARNI), may have beneficial effects on cardiac and renal outcomes in patients with HF with reduced ejection fraction, particularly by slowing the rate of decrease in the estimated glomerular filtration rate compared to a single angiotensin-converting enzyme inhibitor.
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