Background: Cardiac regeneration after myocardial infarction (MI) critically depends on the restoration of blood flow to the affected area. Angiogenesis, driven by the dynamic interaction between endothelial cells and pericytes, is therefore pivotal for the cardiac recovery after MI. Abundant in the heart’s dense capillary network, pericytes regulate vascular tone, modulate immune responses, and play a key role in vessel formation, maturation, and stabilization. Leveraging their regenerative and angiogenic properties offers a promising strategy to ischemic heart repair. Myocardial infarction is associated with autonomic imbalance, characterised by reduced vagal activity. Restoring cholinergic input through vagus nerve stimulation has been shown to exert anti-arrhythmic effects, reduce infarct size, promote angiogenesis, and favour myocardial functional recovery. Despite the recognized importance of neurally derived trophic factors in cardiac regeneration, this aspect remains largely underexplored.
Aim: To explore the potential interplay between autonomic neural regulation and pericytes in cardiac regeneration following MI.
Methods: Human cardiac pericytes are isolated from cardiac surgery waste tissue, expanded in vitro and treated with carbachol (cholinergic agonist) or isoprenaline (b-adrenergic agonist) every 24h at rising concentrations. Cell viability is assessed at 24, 48 and 72h using calcein/EthDIII, while proliferation is evaluated using EdU incorporation after 48h of treatment. To measure cell migration speed and efficiency, wound healing assay is used, and migration is observed during a 24-hour period. Immunocytochemistry is employed to investigate the expression of neurotransmitter receptors. To mimic ischemic conditions in vitro, pericytes are cultured under hypoxia and deprived of growth factors for 24h.
Results: At tested concentrations, neither drug had adverse effects on cardiac pericyte viability or morphology. Preliminary data indicate that neither carbachol nor isoprenaline influences cardiac pericyte proliferation. However, both drugs were found to enhance pericyte migration induced by PDGF-BB. Immunostaining revealed that pericytes express neurotransmitter receptors associated with cardioprotection, including α7 nicotinic and M3 muscarinic acetylcholine receptor.
Conclusion:These findings suggest that autonomic neurotransmitters may enhance pro-angiogenic function of pericytes, supporting the notion that neural modulation contributes to myocardial regeneration. Ongoing studies will further characterize neuroactivated pericytes and downstream signaling pathways involved in vascular repair, guiding future regenerative therapies.