Reduced expression of let-7f activates TGF-β/ALK5 pathway and leads to impaired ischaemia-induced neovascularization after cigarette smoke exposure.

ABSTRACT: This study sought to determine the potential role of microRNAs (miRNAs) in the detrimental effects of cigarette smoke on angiogenesis and neovascularization. Using large-scale miRNA profiling and qRT-PCR analyses, we identified let-7f as a pro-angiogenic miRNA which expression is significantly reduced in HUVECs treated with cigarette smoke extracts (CSE), and in the ischemic muscles of mice that are exposed to cigarette smoke (MES). In a mouse model of hindlimb ischaemia, intramuscular injection of let-7f mimic restored ischaemia-induced neovascularization in MES. Doppler flow ratios and capillary density in ischemic muscles were significantly improved in MES treated with let-7f mimic. Clinically, this was associated with reduced ambulatory impairment and hindlimb ischaemic damage. Treatme

SUBMITTER: Dhahri W 

PROVIDER: S-EPMC5571564 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature