Abstract
Acute myocardial infarction (MI) evokes a systemic inflammatory response and locally the degradation of the necrotic tissue, followed by scar formation. The mechanisms for containment of the infarct zone are not studied well. The study aimed to examine the response of healthy cardiomyocytes to serum of patients with myocardial infarction. Human iPSC-cardiomyocytes (iPSC-CM) generated from two healthy donors were incubated with serum of patients with MI with and without ventricular fibrillation (VF) or of healthy controls. Different cell adhesion molecules were studied by flow cytometry and immunostaining. Cellular electrophysiology was studied by patch clamp. The cell adhesion molecules CD54/ICAM-1, CD58/LFA-3 and CD321/JAM-A were expressed on iPSC-CM within the plasma membrane. Incubation with serum of MI patients reduced the levels of expression of CD54/ICAM-1 and CD321/JAM-A by 15–20%. VF serum was less effective than serum of MI patients without VF. MI serum or VF serum did not affect resting potential, action potential duration or maximum depolarization velocity. Myocardial infarction serum exerts anti-inflammatory effects on healthy cardiomyocytes without affecting their electrical activity, thus helping to contain the infarct zone and to protect healthy tissue. Ventricular fibrillation during MI drives healthy cardiomyocytes towards a pro-inflammatory phenotype.
Highlights
The study was approved by the Ethics Committee of the Medical Faculty Mannheim, University of Heidelberg and by the Ethics Committee of University Medical Center Göttingen, and carried out in accordance with the approved guidelines
Venous blood of patients presenting with acute myocardial infarction (ST-segment elevation infarction, STEMI, or non-ST-segment elevation infarction, NSTEMI) was collected within the first
Human iPS cells were generated from primary human fibroblasts derived from skin biopsies of two different healthy donors
Summary
At day 25, the percentage of cardiomyocyte positive for the adhesion molecules relative to all cardiomyocytes (as defined by positive expression of troponin I [TNNT2]) was 25.5%, 26.8% and 69.6% for CD54/ ICAM-1, CD58/LFA-3 and CD321/JAM-A, respectively (Fig. 2C). Serum of myocardial infarction affects levels of cell adhesion molecule expression. In addition to the effects on cell numbers, incubation of cardiomyocytes with serum of patients with myocardial infarction (MI) for 48 hours resulted in changes of the expression levels of the different cell adhesion molecules, as expressed by the median fluorescence intensity (MIF) of each marker. CD58/LFA-3 expression levels normalized to cell numbers were not changed by addition to MI serum compared to control serum (p > 0.05, Fig. 4A). If VF serum was used, significantly higher expression of all three cell adhesion molecules was observed compared to serum of patients without VF (Fig. 5). Treating cardiomyocytes with either serum had no significant effects on resting potential (RP), action potential amplitude (APA) or duration (APD), or maximum depolarization velocity (Vmax), as shown in Figs 6 and 7
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