Background: The left ventricular remodeling (LVR) process has limited the effectiveness of therapies after myocardial infarction. The relationship between autoantibodies activating AT1R‐AAs (angiotensin II receptor type 1‐AAs) and ETAR‐AAs (autoantibodies activating endothelin‐1 receptor type A) with myocardial infarction has been described. Among patients with ST‐segment–elevation myocardial infarction, we investigated the relationship between these autoantibodies with LVR and subsequent major adverse cardiac events. Methods and Results: In this prospective observational study, we included 131 patients with ST‐segment–elevation myocardial infarction (61±11 years of age, 112 men) treated with primary percutaneous coronary intervention. Within 48 hours of admission, 2‐dimensional transthoracic echocardiography was performed, and blood samples were obtained. The seropositive threshold for AT1R‐AAs and ETAR‐AAs was >10 U/mL. Patients were followed up at 6 months, when repeat transthoracic echocardiography was performed. The primary end points were LVR, defined as a 20% increase in left ventricular end‐diastolic volume index, and major adverse cardiac event occurrence at follow‐up, defined as cardiac death, nonfatal re‐myocardial infarction, and hospitalization for heart failure. Forty‐one (31%) patients experienced LVR. The prevalence of AT1R‐AAs and ETAR‐AAs seropositivity was higher in patients with versus without LVR (39% versus 11%, P <0.001 and 37% versus 12%, P =0.001, respectively). In multivariable analysis, AT1R‐AAs seropositivity was significantly associated with LVR (odds ratio [OR], 4.66; P =0.002) and represented a risk factor for subsequent major adverse cardiac events (OR, 19.6; P =0.002). Conclusions: AT1R‐AAs and ETAR‐AAs are associated with LVR in patients with ST‐segment–elevation myocardial infarction. AT1R‐AAs are also significantly associated with recurrent major adverse cardiac events. These initial observations may set the stage for a better pathophysiological understanding of the mechanisms contributing to LVR and ST‐segment–elevation myocardial infarction prognosis.

Structural valve deterioration (SVD) of bioprosthetic heart valves (BHVs) has great clinical and economic consequences. Notably, immunity against BHVs plays a major role in SVD, especially when implanted in young and middle-aged patients. However, the complex pathogenesis of SVD remains to be fully characterized, and analyses of commercial BHVs in standardized-preclinical settings are needed for further advancement. Here, we studied the immune response to commercial BHV tissue of bovine, porcine, and equine origin after subcutaneous implantation into adult α1,3-galactosyltransferase-knockout (Gal KO) mice. The levels of serum anti-galactose α1,3-galactose (Gal) and -non-Gal IgM and IgG antibodies were determined up to 2 months post-implantation. Based on histological analyses, all BHV tissues studied triggered distinct infiltrating cellular immune responses that related to tissue degeneration. Increased anti-Gal antibody levels were found in serum after ATS 3f and Freedom/Solo implantation but not for Crown or Hancock II grafts. Overall, there were no correlations between cellular-immunity scores and post-implantation antibodies, suggesting these are independent factors differentially affecting the outcome of distinct commercial BHVs. These findings provide further insights into the understanding of SVD immunopathogenesis and highlight the need to evaluate immune responses as a confounding factor.

Antibody-mediated rejection (AMR) is the leading cause of premature kidney transplant failure. The role of alloantibodies against Human Leukocyte Antigens (HLA) has been a primary focus in AMR. More recently autoantibodies and alloantibodies against the angiotensin II receptor type 1 (AT1R) and the endothelin A receptor (ETAR) have been linked to poor allograft outcomes in kidney transplantation. Nevertheless, evidence supporting routine testing remains insufficient. ELISA testing for anti-AT1R and anti-ETAR antibodies was performed in a pediatric renal transplant cohort. We selected 12 pediatric recipients who had undergone protocol biopsies and antibody measurements at 6 and 24 months post-transplant. Immunohistochemistry was performed on biopsies for AT1R and ETAR as well as the adhesion molecules ICAM-1 and VCAM-1. The analysis showed that ICAM-1 and VCAM-1 expression was significantly increased, along with the presence of circulating antibodies, in patients at 24 months post-transplant compared to patients without circulating antibodies. The presence of anti-AT1R and anti-ETAR antibodies does not seem to influence the expression of their receptors in the transplanted organ. Instead, the increase in adhesion molecules may precede the development of histological damage. Therefore, enlarging the cohort and extending long-term observation would help to understand the impact of anti-AT1R and anti-ETAR antibodies after transplantation.

Structural valve deterioration (SVD) remains a key limitation in bioprosthetic heart valve (BHV) usage influenced by patient age. A deeper understanding of SVD pathogenesis, particularly of the immune-mediated processes altering current BHV materials, is therefore critical. To this end, commercially available BHV tissues of bovine, porcine, and equine origin were investigated following subcutaneous implantation into α1,3-galactosyltransferase-knockout (Gal KO) mice. We compared the immune responses between adult and aged animals via histological assessments of explants and measurement of serum anti-galactose α1,3-galactose (Gal) and anti-non-Gal antibodies at 2 months post-implantation. In contrast to adult mice, old Gal KO mice did not show increased levels of serum anti-Gal or -non-Gal antibodies after receiving specific BHV tissue (i.e., Freedom-Solo). Instead, a significant decrease in serum anti-Gal IgM was found in old recipients of Freedom-Solo. Furthermore, the overall cellular immune response was attenuated in explants from old mice compared with adults (i.e., ATS 3f and Crown). Nevertheless, the Freedom-Solo (bovine) and the Hancock-II (porcine) tissues still elicited strong cellular immune infiltration in the old cohorts. Therefore, the Gal KO mouse model offers a valuable platform to investigate age-related differences regarding cellular and humoral immune responses to various BHV tissues, contributing to our understanding of SVD.