The effects of acetylated cordycepin derivatives on promoting vascular angiogenesis and attenuating myocardial ischemic injury

Abstract

BackgroundEnhanced angiogenesis following myocardial infarction (MI) is beneficial to preserve cardiac function. The present study aimed to investigate whether acetylated derivatives of cordycepin altered its original antitumor properties and exerted cardioprotective effects by promoting angiogenesis in vitro and in vivo. MethodsCordycepin and its derivatives with single (DA), double (DAA), and triple acetyl groups (DAAA) were assessed. The cell viability of leukemia U937 cells, malignant hepatoma Huh-7 cells, and human umbilical vascular endothelial cells (HUVECs) treated with cordycepin, DA, DAA, and DAAA were determined. The expression of β-catenin in U937 cells, as well as the expression of p65, p38 and other related signal regulators in HUVECs elicited by lipopolysaccharides (LPS) were also observed. Angiogenesis was determined by tube formation in HUVECs and Matrigel plug assay in mice. Cardiac function following administration of DAAA was evaluated in mice MI model simulated by coronary artery ligation. ResultsThe inhibitory effects of cordycepin and its acetylated derivatives on U937 cells, Huh-7 cells, HUVECs, and the expression of β-catenin in U937 cells were mitigated with increasing acetylation. Intriguingly, DAAA preserved the cell viability of HUVECs compared to other acetylated derivatives. Although DAAA had a significantly diminished antitumor effect compared to cordycepin, it promoted angiogenesis in mice and tube formation in HUVECs and attenuated LPS-induced phosphorylation of p65 and p38. Additionally, administration of DAAA improved cardiac function following coronary artery ligation in mice. ConclusionDAAA could be considered a promising adjunctive therapy to prevent post-MI heart failure through promoting angiogenesis.