The angiogenic neuropeptide catestatin exerts beneficial effects on human coronary vascular cells and cardiomyocytes

Introduction: Myocardial infarction (MI) induces irreversible tissue damage, eventually leading to heart failure. Exogenous induction of angiogenesis positively influences ventricular remodeling after MI. Recently, we could show that therapeutic angiogenesis by the neuropeptide catestatin (CST) restores perfusion in the mouse hind limb ischemia model by the induction of angio-, arterio-and vasculogenesis. Thus, we assumed that CST might exert beneficial effects on cardiac cells.Methods/results: To test the effect of CST on cardiac angiogenesis in-vitro matrigel assays with human coronary artery endothelial cells (HCAEC) were performed. CST significantly mediated capillary like tube formation comparable to vascular endothelial growth factor (VEGF), which was used as positive control. Interestingly, blockade of bFGF resulted in abrogation of observed effects. Moreover, CST induced proliferation of HCAEC and human coronary artery smooth muscle cells (HCASMC) as determined by BrdU-incorporation. Similar to the matrigel assay blockade of bFGF attenuated the effect. Consistent with these findings western blot assays revealed a bFGF-dependent phosphorylation of extracellular-signal regulated kinase (ERK) 1/2 by CST in these cell lines. Finally, CST protected human cardiomyocytes in-vitro from apoptosis. Conclusion: CST might qualify as potential candidate for therapeutic angiogenesis in MI.

Automated summary

Myocardial infarction (MI) causes irreversible tissue damage and eventual heart failure. Therapeutic angiogenesis using the neuropeptide catestatin (CST) has shown to restore perfusion in a mouse hind limb ischemia model. CST promotes capillary like tube formation, cell proliferation, and protects cardiomyocytes from apoptosis, indicating its potential as a therapy for MI.