Comparative Analysis of Porcine Plasma from Acute Myocardial Infarction with or without Occlusion of the Coronary Arteries (MINOCA versus MI) Reveal Distinct Differently Induced Endothelial Cells Responses In Vitro

Background: Patients with a myocardial infarction with non-obstructive coronary arteries (MINOCA) suffer from many small and scattered microinfarctions that cause severe cardiac damage due to omitted oxygen supply. These occlusions are not visible by routine cardiac catheterization examination. Instead, time-consuming imaging procedures are necessary, which delay the appropriate therapeutic treatment. As a result, MINOCA is associated with a high mortality rate and a high risk for serious complications.

Methods: Since research on MINOCA is still in its early stages, we aimed to understand how endothelial cells are affected in this disease’s early stage, and how these effects compare with classical myocardial infarction (MI). For that purpose, we utilized a novel porcine animal model that mimics all clinically relevant aspects of MINOCA by autologous micro-thrombo-embolization. Additionally, an animal control group was included that mirrors a classical myocardial infarction (MI) by balloon occlusion of the coronary arteries. Plasma samples were collected before and 30 minutes after induction of either myocardial obstruction. Human endothelial cells (HUVECs) were treated up to 48 hours with plasma of MINOCA, MI, and healthy controls (n ≥ 8). Afterwards, we analyzed for phenotypical and functional changes of HUVECs.

Results: Our results showed that while nitric oxide synthase activity was equally diminished in both MI and MINOCA compared with healthy controls, MINOCA significantly increased apoptosis and reduced tube formation capacity of HUVECs. The later anti-angiogenic effect even persisted after plasma was removed. The screening of mRNA expression with an endothelial cell panel revealed promising candidates that might explain differences in the observed endothelial dysfunction, like endothelin-2 expression. Further investigations will shed light whether these observations are connected with functional differences of HUVECs when treated with MINOCA plasma.

Conclusion: In general, our findings indicate that MINOCA is distinct from MI and warrants further research. Moreover, we hope to identify certain pathways or regulated molecules, so-called biomarkers, that would enable an early and non-invasive diagnosis as well as adjustments of the current therapeutic treatment of MINOCA.

Publikationsverlauf

Artikel online veröffentlicht:
11. Februar 2025