Roles of TRPV4 in Regulating Circulating Angiogenic Cells to Promote Coronary Microvascular Regeneration.

To clarify the mechanisms underlying TRPV4 regulating angiogenesis by enhancing the activity of CACs, we detected the angiogenesis ability of HUVEC co-cultured with CACs, the effects of ILK on TRPV4 expression and CACs activity, and the impacts of TRPV4 agonist or inhibitor on cardio-protection of AMI rats with or without CAC transplantation. ILK overexpression or TRPV4 agonist promoted the angiogenesis in HUVEC co-cultured with CACs. ILK overexpression or activation upregulated TRPV4 expression in CACs, while TRPV4 agonist stimulation also regulated ILK expression. TRPV4 agonist effectively improved the myocardial function of AMI rats. Moreover, this effect could be strengthened when combined with CAC transplantation, as CAC transplantation dramatically upregulated the expression of ILK and TRPV4 in heart tissues of AMI rats. Thus, the application of TRPV4 agonist may maintain the activity of CACs to promote angiogenesis and microcirculation reconstruction in the area of myocardial infarction and substantially improve the therapeutic effect.