2. Academic Validation
  3. Cardiac mural cells are rate-limiting for coronary vascularization after heart injury

Cardiac mural cells are rate-limiting for coronary vascularization after heart injury

  • iScience. 2025 Sep 10;28(10):113536. doi: 10.1016/j.isci.2025.113536.
Zhengkai Lu 1 2,  Jian Zhou 3,  Min Ye 2,  Jufeng Meng 2,  Teng Feng 2,  Zhen Jiang 2,  Wenxuan Dai 4,  Defang Deng 2,  Lei Yan 2,  Yuanxin Wei 2,  Wen Zhang 2,  Jialei Zheng 2,  Yutao Fu 5,  Chao-Po Lin 2,  Huiwen Chen 4,  Guocheng Shi 4,  Hui Zhang 2 6,  Juan Tang 1
Affiliations

Affiliations

  • 1 State Key Laboratory of Cardiology and Medical Innovation Center, Shanghai East Hospital, School of Life Science and Technology, Frontier Science Center for Stem Cell Research, Tongji University, Shanghai 200092, China.
  • 2 School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China.
  • 3 Department of Cardiovascular Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200092, China.
  • 4 Department of Cardiothoracic Surgery, Congenital Heart Center, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China.
  • 5 Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Tongji Hospital affiliated to Tongji University, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
  • 6 State Key Laboratory of Advanced Medical Materials and Devices, ShanghaiTech University, Shanghai 201210, China.
PMID: 41069851 DOI: 10.1016/j.isci.2025.113536
Abstract

Limited angiogenic potential of coronary vascular endothelial cells (cVECs) poses a significant barrier to effective therapeutic revascularization after myocardial infarction (MI). However, the underlying mechanisms of restricted vascularization post-MI remain unclear. Here, we demonstrate that both reduced density and limited proliferation of mural cells result in inadequate mural cell coverage of coronary vessels, consequently impeding coronary vascularization within the MI heart. Our findings reveal that the cell cycle inhibitor Phosphatase and tensin homolog (PTEN) is expressed in mural cells from both sham-operated and MI hearts. Conditional PTEN deletion in mural cells enhances mural-derived cell (MDC) proliferation, increases coronary vascular density, promotes arteriogenesis, and improves cardiac function following MI. Furthermore, PTEN deficiency upregulates chemokine C-X-C motif ligand 12 expression, which potentially reduces Apoptosis in cVECs and MDCs and increases vascular density. These results identify cardiac mural cells as promising therapeutic targets for enhancing coronary angiogenesis and vascular remodeling after ischemic injury.

Keywords

Cardiovascular medicine; Cell biology.

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