CCL28 contributes to angiogenesis and cardiac repair through CCR10+ endothelial cells after myocardial infarction in male mice
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<sup>-</sup> ECs, CCR10<sup>+</sup> 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.
Authors
- Kaiyang Lin (ORCID: https://orcid.org/0000-0003-1421-2728)
- Jiaran Shi (ORCID: https://orcid.org/0000-0002-2020-0830)
- Hanchuan Chen (ORCID: https://orcid.org/0000-0002-6654-4129)
- Juntao Chen (ORCID: https://orcid.org/0000-0003-4376-2390)
- Kun Yang (ORCID: https://orcid.org/0000-0001-7908-2675)
- Rifeng Gao (ORCID: https://orcid.org/0000-0002-5453-8899)
- Yang Lyu (ORCID: https://orcid.org/0000-0002-4353-0082)
- Wei Wei (ORCID: https://orcid.org/0000-0001-8110-0705)
- Biting Lin
- Xiang Wei (ORCID: https://orcid.org/0000-0002-7557-0919)
- Yunzhi Ling
- Gengyu Zhou
Institutions
- Fujian Medical University (CN)
- Shanghai Jiao Tong University (CN)
- Fudan University (CN)
- Ruijin Hospital (CN)
- Shanghai Chest Hospital (CN)
- Education Department of Fujian Province (CN)
- Ningbo Medical Center Lihuili Hospital (CN)
- Shanghai Institute of Hypertension (CN)
- Fujian Provincial Hospital (CN)
- Second Affiliated Hospital of Zhejiang University (CN)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-10-20
- DOI
- https://doi.org/10.1038/s41467-025-64283-4
- Citations
- 1
- Primary Topic
- Peptidase Inhibition and Analysis
- Type
- article
- Field-Weighted Citation Impact
- 1.05