Pluto Bioinformatics

GSE127854: Repurposing an anti-cancer drug for the treatment of hypertrophic heart disease

Bulk RNA sequencing

Coronary microvascular dysfunction combined with maladaptive cardiomyocyte morphology and energetics are major contributors towards heart failure advancement. Thus dually enhancing cardiac angiogenesis and targeting cardiomyocyte function to slow, or reverse, the development of heart failure is a logical step towards improved therapy. We present evidence for the potential to repurpose a former anti-cancer Arg-Gly-Asp (RGD)-mimetic pentapeptide, Cilengitide, here used at low doses. Cilengitide targets avb3 integrin and this integrin is upregulated in human dilated and ischemic cardiomyopathies. Treatment of mice after transverse aortic constriction (TAC) surgery with low dose Cilengitide (ldCil) enhances coronary angiogenesis and directly affects cardiomyocyte hypertrophy with a correlating reduction disease severity. At a molecular level ldCil treatment has a direct effect on cardiac endothelial cell transcriptomic profiles with a significant enhancement of proangiogenic signalling pathways, corroborating the enhanced angiogenic phenotype after ldCil treatment. SOURCE: Eleni Maniati ( - Cancer and Inflammation Queen Mary University of London

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