ArticleThe Journal of clinical investigation2022
Cardiac pericyte reprogramming by MEK inhibition promotes arteriologenesis and angiogenesis of the ischemic heart.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 43 citations in OpenAlex.
- The mechanism of vascular injury caused by polystyrene microplastics: Involving ferroptosis and metabolomics.iScience · 2026Article
- Targeting the ERK Signaling Pathway to Halt Adventitia Remodeling of Ascending Thoracic Aortic Aneurysm.JACC. Basic to translational science · 2026Article
- Review
- Proliferation-dependent adipogenic differentiation of progenitor cells in rat coronary artery explants.Stem cell research & therapy · 2026Article
- GLP-1 activates KNature communications · 2026Article
- Deficiency of fibroblast growth factor 2 promotes contractile phenotype of pericytes in ascending thoracic aortic aneurysm.American journal of physiology. Heart and circulatory physiology · 2025Article
- Hypertension research 2024 update and perspectives: basic research.Hypertension research : official journal of the Japanese Society of Hypertension · 2024Review
- Healthy longevity-associated protein improves cardiac function in murine models of cardiomyopathy with preserved ejection fraction.Cardiovascular diabetology · 2024Article
- Pericyte phenotype switching alleviates immunosuppression and sensitizes vascularized tumors to immunotherapy in preclinical models.The Journal of clinical investigation · 2024Article
- Generation and characterisation of scalable and stable human pluripotent stem cell-derived microvascular-like endothelial cells for cardiac applications.Angiogenesis · 2024Article
- MEK/ERK signaling drives the transdifferentiation of supporting cells into functional hair cells by modulating the Notch pathway.Stem cells translational medicine · 2024Article
- MEK inhibitor PD0325901 upregulates CD34 expression in endothelial cells via inhibition of ERK phosphorylation.Regenerative therapy · 2024Article
- Macrophages upregulate mural cell-like markers and support healing of ischemic injury by adopting functions important for vascular support.Nature cardiovascular research · 2024Article
- The role of cardiac pericytes in health and disease: therapeutic targets for myocardial infarction.Nature reviews. Cardiology · 2024Review
- Pericytes in the disease spotlight.Trends in cell biology · 2024Review
- MEK inhibitors: a promising targeted therapy for cardiovascular disease.Frontiers in cardiovascular medicine · 2024Review
- Cardiac Pericytes Acquire a Fibrogenic Phenotype and Contribute to Vascular Maturation After Myocardial Infarction.Circulation · 2023Article
- Biology and function of pericytes in the vascular microcirculation.Animal models and experimental medicine · 2023Review
- The longevity-associated BPIFB4 gene supports cardiac function and vascularization in ageing cardiomyopathy.Cardiovascular research · 2023Article
- Type H vessel/platelet-derived growth factor receptor βCell proliferation · 2023Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Pericytes (PCs) are abundant yet remain the most enigmatic and ill-defined cell population in the heart. Here, we investigated whether PCs can be reprogrammed to aid neovascularization. Primary PCs from human and mouse hearts acquired cytoskeletal proteins typical of vascular smooth muscle cells (VSMCs) upon exclusion of EGF/bFGF, which signal through ERK1/2, or upon exposure to the MEK inhibitor PD0325901. Differentiated PCs became more proangiogenic, more responsive to vasoactive agents, and insensitive to chemoattractants. RNA sequencing revealed transcripts marking the PD0325901-induced transition into proangiogenic, stationary VSMC-like cells, including the unique expression of 2 angiogenesis-related markers, aquaporin 1 (AQP1) and cellular retinoic acid-binding protein 2 (CRABP2), which were further verified at the protein level. This enabled us to trace PCs during in vivo studies. In mice, implantation of Matrigel plugs containing human PCs plus PD0325901 promoted the formation of αSMA+ neovessels compared with PC only. Two-week oral administration of PD0325901 to mice increased the heart arteriolar density, total vascular area, arteriole coverage by PDGFRβ+AQP1+CRABP2+ PCs, and myocardial perfusion. Short-duration PD0325901 treatment of mice after myocardial infarction enhanced the peri-infarct vascularization, reduced the scar, and improved systolic function. In conclusion, myocardial PCs have intrinsic plasticity that can be pharmacologically modulated to promote reparative vascularization of the ischemic heart.
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