Targeting neuro-immune systems to achieve cardiac tissue repair following myocardial infarction: A review of therapeutic approaches from in-vivo preclinical to clinical studies

Myocardial healing following myocardial infarction (MI) toward either functional tissue repair or excessive scar-ring/heart failure, may depend on a complex interplay between nervous and immune system responses, myocar-dial ischemia/reperfusion injury factors, as well as genetic and epidemiological factors. Hence, enhancing cardiac repair post MI may require a more patient-specific approach targeting this complex interplay and not just the heart, bearing in mind that the dysregulation or modulation of just one of these systems or some of their mech-anisms may determine the outcome either toward functional repair or toward heart failure.In this review we have elected to focus on existing preclinical and clinical in-vivo studies aimed at testing novel therapeutic approaches targeting the nervous and immune systems to trigger myocardial healing toward func-tional tissue repair. To this end, we have only selected clinical and preclinical in-vivo studies reporting on novel treatments targeting neuro-immune systems to ultimately treat MI. Next, we have grouped and reported treatments under each neuro-immune system. Finally, for each treatment we have assessed and reported the re-sults of each clinical/preclinical study and then discussed their results collectively. This structured approach has been followed for each treatment discussed. To keep this review focused, we have deliberately omitted to cover other important and related research areas such as myocardial ischemia/reperfusion injury, cell and gene thera-pies as well as any ex-vivo and in-vitro studies.The review indicates that some of the treatments targeting the neuro-immune/inflammatory systems appear to induce beneficial effects remotely on the healing heart post MI, warranting further validation. These remote ef-fects on the heart also indicates the presence of an overarching synergic response occurring across the nervous and immune systems in response to acute MI, which appear to influence cardiac tissue repair in different ways depending on age and timing of treatment delivery following MI. The cumulative evidence arising from this re-view allows also to make informed considerations on safe as opposed to detrimental treatments, and within the safe treatments to ascertain those associated with conflicting or supporting preclinical data, and those warranting further validation. (c) 2023 Published by Elsevier Inc.

Automated summary

Myocardial healing following myocardial infarction depends on the complex interplay between nervous and immune system responses, ischemia/reperfusion injury factors, as well as genetic and epidemiological factors. Targeting the neuro-immune systems may induce beneficial effects on cardiac tissue repair post MI, indicating an overarching synergic response across these systems.