Similarities between fibroblasts and cardiomyocytes in the study of the permeability transition pore

The investigation of biological processes involved in cardiovascular diseases and the study of new cardioprotective strategies and therapeutic targets in human specimens are challenging to date. This is partly due to the almost absent availability of control cardiac samples caused by stringent ethical guidelines of the interested country and the continual development of semiinvasive percutaneous procedures, which make it difficult to perform and process the cardiac biopsy for experiments on viable myocytes. Real and attractive alternatives may exist, such as the creation of pathological models with immortalised ventricular human myocytes and the direct reprogramming of human endogenous cells into cardiomyocytes using induced pluripotent stem cell technology, but these methods also include limitations.1 The obstacles to developing an appropriate cell model to study a given pathology are not limited to the cardiovascular field. Several studies, including mitochondrial disorders and neurodegenerative diseases,24 have adopted alternative and more feasible experimental models, such as skinbiopsyderived fibroblasts, to perform functional analyses on a pathological phenotype. In our previous publication5 to which this short letter refers, we showed a strong and positive correlation between the mitochondrial permeability transition pore (mPTP) opening measured in fibroblasts from STsegment elevation myocardial infarction (STEMI) patients and reperfusion injury (RI) evaluated by cardiac magnetic resonance imaging of the same patients. Moreover, we found significant intersubject variability in mPTP opening, and the patients with hyperresponsive mPTP opening also had greater reperfusion damage.5 This was an interesting finding considering the fact that, to the best of our knowledge, no data on mPTP and RI in humans are available to date. However, the question of how mPTP measured in fibroblasts reflects the reperfusion damage of a given patient, as well as how mPTP function (or other biological readouts) can be assessed directly in patients affected by cardiac ischaemia– reperfusion (I/R), remains unanswered. mPTP is a multiprotein complex with channel function.611 It is of great interest in the cardiovascular field because it is a key step in cell death during I/R episodes (i.e., in MI) in its “open state” and is considered one of the main culprits of RI. For these reasons, it constitutes an important target for cardioprotection, as already shown in cells and animal models.8,12,13 Here, in an effort to explain our findings mentioned above, we provide an update on the differences that may occur between cardiomyocytes and fibroblasts in the analysis of mPTP activity in ischaemic patients. Indeed, with this pilot study, we detected negligible differences in mPTP function between both cell lines. This study is part of a larger project aimed to provide genetic and functional information on the mPTP in the RI directly in humans and refers to our previous publication.