Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Aug 12:12:1515693.
doi: 10.3389/fcvm.2025.1515693. eCollection 2025.

Prognostic role of angiotensin-II receptor type 1 and endothelin-1 receptor type A agonistic autoantibodies in patients with acute myocardial infarction

Francesco Tona #  1 , Giovanni Civieri #  1 , Marta Vadori  2 , Giulia Masiero  1 , Laura Iop  3 , Martina Perazzolo Marra  1 , Annagrazia Cecere  1 , Marika Martini  1 , Donatella Tansella  1 , Giacomo Bernava  3 , Benedetta Schiavon  1 , Loira Leoni  1 , Emanuele Cozzi  2 , Sabino Iliceto  1   4
Affiliations

Prognostic role of angiotensin-II receptor type 1 and endothelin-1 receptor type A agonistic autoantibodies in patients with acute myocardial infarction

Francesco Tona et al. Front Cardiovasc Med. .

Abstract

Background: Functional autoantibodies against angiotensin II type 1 (AT1R-AAs) and endothelin-1 type A (ETAR-AAs) receptors are associated with microvascular obstruction and myocardial remodeling after ST-elevation myocardial infarction (STEMI). However, their role in the long-term prognosis after STEMI has not been investigated.

Methods: This is a prospective observational study enrolling STEMI patients undergoing early primary PCI. The incidence of major adverse cardiovascular events (MACE) was investigated during the follow-up. Autoantibody seropositivity was defined as a level >10 U/ml.

Results: 200 STEMI patients (89% male, median age 61 years) were enrolled. 110 (55%) were seronegative for both autoantibodies, 44 (22%) were seropositive for one autoantibody, and 46 (23%) were seropositive for both autoantibodies. Over a median follow-up of 1.2 years, the incidence of MACE was higher in patients with double (31%) and single (25%) seropositivity than in seronegative patients (13%, p = 0.02 among groups). Double seropositivity was independently associated with higher risk of MACE (HR 2.386, 95% CI 1.471-3.864, p < 0.001).

Conclusion: AT1R-AAs and ETAR-AAs are associated with an increased risk of MACE after STEMI. Assessment of autoantibody levels paves the way for future therapies targeting specific molecular pathways associated with poor prognosis after an acute coronary event.

Keywords: G protein coupled receptors; acute coronary syndrome; adverse prognosis; autoantibodies; autoimmunity; coronary microcirculation; no-reflow.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Figures

Figure 1
Figure 1
Frequency of MACE in STEMI patients based on serum autoantibody status. MACE in seronegative STEMI patients (left pie chart); MACE in single seropositive (AT1R-AAs or ETAR-AAs seropositive) STEMI patients (middle pie chart); and MACE in double seropositive (AT1R-AAs and ETAR-AAs seropositive) STEMI patients (right pie chart). The P-value for the difference between the groups is reported.
Figure 2
Figure 2
Kaplan–meier curves for MACE at the 4-year follow-up. The Kaplan–Meier curves show significantly higher MACE rates for single- and double-seropositive patients than for seronegative patients. The inset graph shows the data on an expanded y axis.
Figure 3
Figure 3
Spline curves for AT1R-AAs and ETAR-AAs versus MACE. Changes in the hazard ratio (HR) across the AT1R-AAs (A) and ETAR-AAs (B) are demonstrated in spline curves on a hazard scale with overlaid 95% confidence intervals (gray shaded area). This scale shows the relationship between AT1R-AAs, ETAR-AAs, and MACE.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Widimsky P, Wijns W, Fajadet J, De Belder M, Knot J, Aaberge L, et al. Reperfusion therapy for ST elevation acute myocardial infarction in Europe: description of the current situation in 30 countries. Eur Heart J. (2010) 31:943–57. 10.1093/eurheartj/ehp492 - DOI - PMC - PubMed
    1. Mensah GA, Fuster V, Murray CJL, Roth GA, Mensah GA, Abate YH, et al. Global burden of cardiovascular diseases and risks, 1990–2022. J Am Coll Cardiol. (2023) 82:2350–473. 10.1016/j.jacc.2023.11.007 - DOI - PMC - PubMed
    1. Lechner I, Reindl M, Tiller C, Holzknecht M, Fink P, Troger F, et al. Temporal trends in infarct severity outcomes in ST-segment–elevation myocardial infarction: a cardiac magnetic resonance imaging study. JAHA. (2023) 12(15):e028932. 10.1161/JAHA.122.028932 - DOI - PMC - PubMed
    1. Dhaun N, Webb DJ. Endothelins in cardiovascular biology and therapeutics. Nat Rev Cardiol. (2019) 16(8):491–502. 10.1038/s41569-019-0176-3 - DOI - PubMed
    1. Mehta PK, Griendling KK. Angiotensin II cell signaling: physiological and pathological effects in the cardiovascular system. Am J Physiol Cell Physiol. (2007) 292:C82–97. 10.1152/ajpcell.00287.2006 - DOI - PubMed

LinkOut - more resources