Autoantibody positivity against AT1R and ETAR was independently associated with increased prevalence of coronary microvascular obstruction and worse clinical outcomes in STEMI patients.
Cohort (n=287)
Yes
Do agonistic autoantibodies against AT1R and ETAR directly induce coronary microvascular endothelial injury, and does pharmacological receptor blockade mitigate this damage in STEMI patients?
Agonistic autoantibodies against AT1R and ETAR directly damage coronary microvascular endothelium, suggesting that pharmacological blockade of these receptors may represent a novel strategy to prevent microvascular obstruction in high-risk STEMI patients.
Effect estimate: Autoantibody positivity independently associated with CMVO after adjustment (multivariable logistic regression OR, exact number not provided)
p-value: p=<0.05
Background Despite timely primary percutaneous coronary intervention, coronary microvascular obstruction (CMVO) continues to limit myocardial reperfusion and worsen prognosis in patients with ST-elevation myocardial infarction (STEMI). Agonistic autoantibodies targeting the angiotensin II type 1 (AT1R) and endothelin-1 type A (ETAR) receptors have been associated with CMVO, but whether they directly contribute to microvascular injury remains unclear. Methods We prospectively enrolled 287 STEMI patients and evaluated CMVO, left ventricular remodeling, and major adverse cardiovascular events during a median follow-up of 460 days. Immunoglobulins were isolated from a subset of patients with the highest AT1R-AA and ETAR-AA titers and from seronegative controls. Human cardiac microvascular endothelial cells were exposed to patient-derived or control immunoglobulins, with or without pharmacological receptor blockade. Results Patients with higher autoantibody titers showed a greater prevalence of CMVO and worse clinical outcomes. In vitro , immunoglobulins from seropositive patients rapidly induced endothelial dysfunction, characterized by cytoskeletal disorganization, junctional disruption, endothelial activation, and increased mitochondrial oxidative stress. These alterations were most pronounced at 24 hours and progressed to reduced cell viability and increased cytotoxicity at 48 hours. Immunoglobulins from seronegative controls had no relevant effects. Blockade of AT1R and ETAR significantly mitigated endothelial injury and oxidative stress. Conclusions Agonistic autoantibodies against AT1R and ETAR directly damage coronary microvascular endothelium and reproduce key features of CMVO observed in STEMI patients. These findings support a clinically relevant, immune-mediated mechanism of microvascular injury and suggest that receptor antagonism represents a biologically plausible, receptor-dependent mechanism warranting further investigation as a potential microvascular protective strategy in high-risk STEMI patients.
Iop et al. (Wed,) conducted a cohort in Adults with ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention within 12 hours of symptom onset (n=287). Aggression autoantibody positivity against AT1R and ETAR vs. Autoantibody seronegative patients was evaluated on Coronary microvascular obstruction (CMVO) and major adverse cardiovascular events (MACEs: cardiovascular death, nonfatal reinfarction, heart failure hospitalization) (Autoantibody positivity independently associated with CMVO after adjustment (multivariable logistic regression OR, exact number not provided), p=<0.05). Autoantibody positivity against AT1R and ETAR was independently associated with increased prevalence of coronary microvascular obstruction and worse clinical outcomes in STEMI patients.