Versican Promotes Cardiomyocyte Proliferation and Cardiac Repair

• DOI: 10.1161/circulationaha.123.066298
• Publication Date: 2023-10-27T09:01:56Z
• Authors: Jie Feng; Yandong Li; Yan Li; Qianqian Yin; Haotong Li; Jun Li; Bin Zhou; Jian Meng; Hong Lian; Mengge Wu; Yahuan Li; Kefei Dou; Weihua Song; Bin Lu; Lihui Liu; Shengshou Hu; Yu Nie
• Keywords: Versican

BACKGROUND: The adult mammalian heart is incapable of regeneration, whereas a transient regenerative capacity maintained in the neonatal heart, primarily through proliferation preexisting cardiomyocytes. Neonatal regeneration after myocardial injury accompanied by an expansion cardiac fibroblasts and compositional changes extracellular matrix. Whether how these influence cardiomyocyte remains to be investigated. METHODS: We used apical resection infarction surgical models mice investigate matrix components involved injury. Single-cell RNA sequencing liquid chromatography–mass spectrometry analyses were for versican identification. Cardiac fibroblast–specific Vcan deletion was achieved using mouse strains Col1a2-2A-CreER fl/fl . Molecular signaling pathways related effects assessed Western blot, immunostaining, quantitative reverse transcription polymerase chain reaction. fibrosis function evaluated Masson trichrome staining echocardiography, respectively. RESULTS: Versican, fibroblast–derived component, upregulated promoted proliferation. Conditional knockout decreased impaired regeneration. In mice, intramyocardial injection enhanced proliferation, reduced fibrosis, improved function. Furthermore, augmented human induced pluripotent stem cell–derived Mechanistically, activated integrin β1 downstream molecules, including ERK1/2 Akt, thereby promoting repair. CONCLUSIONS: Our study identifies as pro-proliferative proteoglycan clarifies role These findings highlight its potential therapeutic factor ischemic diseases.