Comparative In Vitro Analysis of the Effects of Porcine Plasma from Myocardial Infarction with or without Obstruction of the Coronary Arteries (MI versus MINOCA) on Human Cardiac Fibroblasts

Background: Myocardial infarction (MI) remains one of the most predominant contributors of morbidity and mortality in the developed world. Up to 15% of all patients suffer from myocardial infarction with non-obstructive coronary arteries (MINOCA). It is a heterogeneous condition defined by the absence of significant epicardial coronary artery stenosis. Instead, it presents with an acute myocardial injury due to numerous scattered microinfarctions. A diagnosis of MINOCA is a time-consuming process and no specific therapy is available, which has a detrimental impact on the prognosis of patients. Therefore, the identification of novel diagnostic and therapeutic targets are urgently needed to revolutionize the current management of MINOCA. To accomplish this, it is of necessity to gather insights on the thus far poorly understood pathomechanisms of MINOCA. We hypothesize that cardiac fibroblasts (CFs) play a pivotal role in this process, as they are the primary driver of not only the remodeling process but also of accelerated fibrosis in MI.

Methods: Accordingly, this study aims to elucidate the effect on CFs of MINOCA by investigating induced in vitro alterations of human CFs that were treated for up 72 hours with 5% of plasma specimens from female pigs suffering from acute MINOCA or MI (300 minutes post infarction). Herein, balloon catheterization served to induce MI, while the administration of autologous coronary microthrombi induced MINOCA. Human CFs were additionally treated with healthy porcine plasma and fetal calf serum (FCS), of which both served as control. Subsequently, cells were evaluated for differences in proliferation, apoptosis, differentiation/activation, and extracellular matrix composition.

Results: Our preliminary results demonstrate that neither MINOCA nor MI plasma induced alterations in cell proliferation when compared with healthy or FCS controls as evidenced by cell count or immunofluorescence staining of K_i-67. Similarly, apoptosis levels exhibited comparable levels between all groups as determined by Caspase 3/7 assay.

Conclusion: Further investigations will elucidate whether plasma of MINOCA and MI animals is capable to induce activation, differentiation, and alterations of the extracellular matrix of human CFs. In general, the current study will enable a deeper understanding of the pathophysiology of MINOCA and probably lead to the discovery of novel diagnostic and therapeutic strategies, mitigating myocardial damage and improving outcomes in MINOCA patients.

Publication History

Article published online:
11 February 2025