Abstract
Secretome-based therapies that target angiogenesis are promising for the treatment of ischemic heart disease (IHD). The effects of Chemokine C-C motif ligand (CCL) 28 on IHD remain unclear. In this study, we investigated the role of CCL28 in angiogenesis during IHD in male mice using the myocardial infarction (MI) and hindlimb ischemia (HI) models. The upregulated CCL28/ C-C motif receptor (CCR)10 axis has been observed in HI and MI. Additionally, CCR10 is highly expressed in endothelial cells (ECs). Compared to CCR10- ECs, CCR10+ ECs exhibited robust proangiogenic capacity, which was induced by CCL28 through CCR10/ERK/SOX5 positive feedback signaling. The deletion of CCL28 results in impaired angiogenesis, whereas the use of recombinant CCL28 protein has therapeutic potential for myocardial and hindlimb ischemia, including that in diabetes. Endothelial-specific CCR10 deficiency impairs angiogenesis and blocks the therapeutic effects of rCCL28 in ischemic models. Serum CCL28 levels have a predictive effect on coronary collateral vessels (CCV) in patients with chronic total occlusions. This study highlights the angiogenic role of CCL28 and suggests that recombinant CCL28 protein may be a potential therapeutic option to attenuate IHD.