Effect of Acetylsalicylic Acid on Angiogenesis Through Assessment of Microvascular Density, VEGF-A, Interleukin-1 and PDGF-B Receptors on Rat Myocardium that Undergo Hypobaric Hypoxia Exposure

Abstract Background Myocardial hypoxia in coronary artery disease (CAD) may induce angiogenic response by activating proangiogenic mediators; Vascular Endothelial Growth Factor-A (VEGF-A) and Platelet-derived growth factor (PDGF-B), and proinflammatory mediator Interleukin-1 (Il-1). Acetylsalicylic acid (ASA) was known could reduce tumor growth by inhibiting angiogenesis process. Objective The study aimed to assess the effect of ASA on the angiogenesis in myocardial tissue which induced by hypobaric hypoxia exposure.Methods This was an experimental study with double interventions: hypobaric hypoxia exposure and ASA administration. The subjects were divided equally and randomly into four groups: I) control group without any intervention, II) hypobaric hypoxia exposure only, III) hypobaric hypoxia with low dose of ASA (2mg/kgs), and IV) hypobaric hypoxia with high dose of ASA (10 mg/kgs) for 14 days. Hypobaric hypoxia exposure was performed intermittently in a hypobaric chamber. At the end of the study, rats’ myocardial walls were extracted and examined for their microvascular density with Hematoxylin-Eosin and anti-CD34 immunostaining. The hearts were also studied for the expression of VEGF-A, Interleukin-1 (Il-1), and PDGF-B receptors by immunohistochemistry, and were assessed by histopathology sections using histoscore. Results The study subjects were 32 Wistar rats, aged 18-20 weeks weighing 250-350 grams. There were significant differences in microvascular density in both HE (median 4 vs. 2, p=0.021) and anti CD34 stainings (median 3 vs. 1, p=0.028), as well as VEGF A (median 10.5 vs. 3, p=0.002) and Il-1 (median 10.5 vs 3.5, p=0.004) receptors expressions between ASA and without ASA groups. Furthermore, there were differences in microvascular density using anti-CD34 (median 3 vs. 1, p=0.035) and VEGF-A receptor expression (median 6 vs. 2, p=0.022) between low dose and high dose of ASA group. Conclusion The administration of ASA may decrease angiogenic response of hypobaric hypoxia exposure. High dose of ASA may reduce angiogenesis process stronger than low dose of ASA.