Abstract
Acute myocardial infarction initiates a cascade of events including loss of protein homeostasis and chronic inflammation that affect overall cellular repair and senescence. This contributes to loss of cardiomyocytes and consequent formation of fibrotic scar. In certain vertebrate species, the heart can completely self-repair or regenerate after myocardial injury; however, this does not appear to be the case for humans. Despite this limitation, studies using novel non-pharmacologic interventions designed to protect against ischemic damage and to improve patient outcomes are ongoing. Remote ischemic conditioning stratagems are used to attenuate ischemia-reperfusion injury in clinical and animal studies; endogenous protective factors that stimulate complex signal transduction pathways are deemed responsible. Some of these factors could conceivably act in concert with those involved in regulating cardiovascular regeneration. Numerous studies have focused on cardiac regenerative interventions using stem-cell based therapies and transplantation of cardiomyocyte (or other cell types) or biocompatible matrices. This review discusses recent progress of pre-clinical and clinical translational studies for cardiac regeneration. In addition, we submit that interventions using cellular adjunctive therapies combined with remote ischemic conditioning may prove to be of interest in the battle to find novel strategies for protection against cardiac injury.
Highlights
Ischemic heart disease is a leading cause of mortality [1] [2]
We submit that interventions using cellular adjunctive therapies combined with remote ischemic conditioning may prove to be of interest in the battle to find novel strategies for protection against cardiac injury
The adult human heart is limited in its capacity to regenerate, or to self-repair; [4] this is in contrast to other species that are able to repopulate ischemic myocardium with minimal scar formation [5] [6]
Summary
Even though reperfusion is effective in patients, other strategies to regenerate damaged myocardium include transplantation of stem cells or cardiomyocytes, e.g. bone marrow-derived cells, resident cardiac cells, skeletal myoblasts, etc. E.g. preconditioning, postconditioning, preconditioning, remote conditioning, etc., the heart with repetitive episodes of non-lethal occlusion-reperfusion stimulates cellular protection pathways in animals and humans and protects myocardium and coronary vessels against injury [14] [15]. This review discusses relevant translational studies with regard to cardiac regeneration as well as the potential influence of remote cardiac conditioning on ischemic injury. The literature search used MEDLINE and PubMed and was combined with a free search; keywords included angiogenesis, cardiac conditioning, cardiac regeneration, cardiomyocyte proliferation, cardioprotection, myocardial cell injury and stem cells
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