Why the study?
Most cardioprotective strategies aiming to reduce infarct size have failed clinically, leaving cardioprotection after acute myocardial infarction as an unmet clinical need.
Does post-conditioning alter the mitochondrial proteomic signature compared to direct revascularization in a swine model of acute myocardial infarction?
Does post-conditioning alter the mitochondrial proteomic signature compared to direct revascularization in a swine model of acute myocardial infarction?
Post-conditioning in a swine model of AMI promotes metabolic reprogramming and a protective mitochondrial response mediated by VDAC2 and DJ-1, offering potential new targets for cardioprotection.
Post-conditioning alters mitochondrial proteome in preclinical models; leaves open clinical translation for infarct size reduction.
Infarct size is the major risk predictor for developing heart failure after an acute myocardial infarction (AMI). The discovery of the conditioning phenomena (i.e., repetitive brief cycles of ischemia applied either before or after a prolonged ischemic insult) has highlighted the existence of endogenous protective mechanisms of the heart potentially limiting infarct size after revascularization. However, most cardioprotective strategies, aiming at infarct size reduction, have failed in clinical studies. Thus, cardioprotection is an unmet clinical need. In the present study, we took a network-assisted systems biology approach to explore the mitochondrial proteomic signature of the myocardium after ischemia, ischemia with direct revascularization, and ischemia with re-establishment of blood flow by post-conditioning in a swine model of AMI. Furthermore, network extension with the ENCODE project human regulatory data allowed the prediction of potential transcription factors at play in the response to post-conditioning of the myocardium. Collectively, our results identify cardiac metabolism as a driver of cardioprotection, highlighting a dual role for post-conditioning promoting metabolic reprogramming of the myocardium, and a protective response mediated by VDAC2 and DJ-1 in the mitochondria.
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Gallinat et al. (2022) studied this question.
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