Abstract
Coronary heart disease (CHD) is a leading cause of death worldwide, and angiogenesis plays important roles in CHD. Thus, in the present study, the angiogenic efficacy of four common cardiovascular medicines (aspirin, pravastatin, metoprolol and isosorbide mononitrate (ISMN)) was determined by the number and length of zebrafish intersegmental vessels (ISVs) after immersing zebrafish embryos in different medicines. Results showed that ISMN significantly increased the length and number of ISVs. ISMN is a long-acting nitrate ester drug. It has been used as a vasodilator to dilate arteries and veins to reduce the cardiac preload and postload. However, the effect of ISMN on angiogenesis remains unclear. Thus, by in vitro experiments, the angiogenic mechanism of ISMN was evaluated through detecting the viability and proliferation of human umbilical vein endothelial cells (HUVECs) and the expression of angiogenesis-related genes and miRNAs. Results indicated that ISMN could increase the viability and proliferation of HUVECs by decreasing apoptosis, and elevated the expressions of vedf, kdrl, pdgfr in zebrafish embryos. Furthermore, the expressions of miR-126, miR-130a and miR-210 were also regulated in ISMN-treated HUVECs. In conclusion, ISMN could promote angiogenesis in zebrafish embryos and HUVECs, implying ISMN may be a potential therapeutic in treating angiogenesis-related diseases.
Highlights
Coronary heart disease (CHD) is still the major cause of death in the world even if the past 20 years witnessed a dramatic decline (Colquhoun et al, 2000; Capewell and O’Flaherty, 2008; Jones and Greene, 2013)
Angiogenesis therapy was once considered as an alternative to traditional revascularization in no-option patients, but recently, it has opened unprecedented opportunities for CHD treatment (Emanueli and Madeddu, 2006)
We investigated the angiogenic effects of different cardiovascular drugs, including aspirin, pravastatin, metoprolol and ISMN
Summary
Coronary heart disease (CHD) is still the major cause of death in the world even if the past 20 years witnessed a dramatic decline (Colquhoun et al, 2000; Capewell and O’Flaherty, 2008; Jones and Greene, 2013). Research found that angiogenesis plays central roles in the pathological process of CHD (Zhang et al, 2018). Angiogenesis was modulated by a subset of signaling pathways including vascular endothelial growth factor (Vegf)-Vegfr, Tie-angiopoietin, transforming growth factor (TGF)-beta, platelet-derived growth factor (Pdgf), and integrins (Warren and Iruela, 2010). In recent years, miRNAs have been reported to regulate various stages of angiogenesis. MiRNA’s capacity to target genes within a signaling pathway makes them promising target for anti-angiogenesis drugs (Tiwari et al, 2018). It is demonstrated that a few specific miRNAs, such as miR-126, miR-210, 221 and 222, could regulate angiogenesis process (Poliseno et al, 2006; Chen and Gorski, 2008; Urbich et al, 2008)
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