Nucleoside Transport Inhibition by Dipyridamole Prevents Angiogenesis Impairment by Homocysteine and Adenosine

Abstract

-Purpose. Adenosine plays an important role in the pathogenesis of homocysteine-associated vascular complications. Methods: This study examined the effects of dipyridamole, an inhibitor for nucleoside transport, on impaired angiogenic processes caused by homocysteine and adenosine in human cardiovascular endothelial cell line (EAhy926). Results: The results showed that dipyridamole restored the extracellular adenosine and intracellular S-adenosylhomocysteine concentrations disrupted by the combination of homocysteine and adenosine. Dipyridamole also ameliorated the impaired proliferation, migration and formation of capillary-like tubes of EAhy926 cells caused by the combination of homocysteine and adenosine. Mechanism analysis revealed that dipyridamole induced the phosphorylation of mitogen-activated protein kinase kinase (MEK) and extracellular signal-regulated kinases (ERK) and its effect on cell growth was attenuated by the MEK inhibitor, U0126. Conclusion: Dipyridamole protected against impaired angiogenesis caused by homocysteine and adenosine, at least in part, by activating the MEK/ERK signalling pathway, and this could be associated with its effects in suppressing intracellular S-adenosylhomocysteine accumulation. Novelty of the Work: This is the first paper showing that nucleoside transport inhibition by dipyridamole reduced impaired angiogenic process caused by homocysteine and adenosine.

Synergistic Effects of Danshen (Salvia Miltiorrhizae Radix et Rhizoma) and Sanqi (Notoginseng Radix et Rhizoma) Combination in Angiogenesis Behavior in EAhy 926 Cells

“…Consistent with the previous findings [ 27 , 33 , 34 ], we have successfully established the Hcy-impaired cell proliferation, migration and tube formation model on EAhy 926 cells. Our results showed that Hcy and Ado impaired angiogenesis in these three assays in a concentration and time-dependent manner.…”

“…In recent years, there is increasing evidence to suggest the importance of Hcy as a new and important risk factor/independent predictor for vascular diseases such as ischaemic heart diseases and stroke. An accumulation of Hcy, often referred to as hyperhomocysteinaemia, has been shown to concentration-dependently impair endothelial cell proliferation and survival together with Ado and ultimately lead to vascular dysfunction [ 25 , 26 , 27 ]. It is suggested that increased extracellular level of hyperhomocysteinaemia in response to cell injury and stress (i.e., ischemia) with Ado [ 28 , 29 ] produces elevated extracellular S-adenosylhomocysteine which in turn, reduces the intracellular mRNA and protein expressions of fibroblast growth factor (FGF2) via G-protein receptor thus, leading to endothelial anti-proliferation (Hcy = 50–100 µM) and anti-survival activity (Hcy > 100 µM) [ 30 , 31 , 32 ].…”

Effects of Adenosine A2A Receptor Agonist on Histopathology of Some Oral Tissues in Rabbits

“…Adenosine is a multifunctional molecule dynamically involved in different tissues and responses in the body. It has been associated largely with the pathogenesis of vascular problems (Kam et al, 2015). One of the present study conduction was to evaluate ADA and GSH levels in adenosine treated rabbits, the results showed highly signi icant mean levels of ADA in adenosine group when compared to controls, this can be explained by fact that ADA is one of the enzymes that are responsible for adenosine activity.…”

“…This angiogenic ability of adenosine could explain the results of the present study manifested by increased vascularity, congestion of blood vessels and hemorrhage. Although the mechanism by which adenosine induces angiogenesis is poorly understood, numer-ous studies have shown that the exogenous adenosine as well as endogenous adenosine can modulate VEGF expression and other angiogenic factors (Kam et al, 2015;Maugeri et al, 2019). in a different cell types.…”