Post-walking angiogenic and vasodilatory responses in men and women with Peripheral Artery Disease: role of microRNA-126

• Grant number: 22/04073-1
• Support Opportunities: Regular Research Grants
• Duration: April 01, 2023 - March 31, 2025
• Field of knowledge: Health Sciences - Physical Education
• Principal Investigator: Natan Daniel da Silva Junior
• Grantee: Natan Daniel da Silva Junior
• Host Institution: Escola de Educação Física e Esporte (EEFE). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Anthony Scott Leicht ; Cláudia Lúcia de Moraes Forjaz ; Nelson Wolosker ; Tiago Fernandes

Abstract

Peripheral arterial disease (PAD) is a clinical manifestation of atherosclerosis that affects the arteries that supply, mainly, the lower limbs. Intermittent claudication (IC), a symptom of PAD, refers to pain, cramping, tingling that occurs in the lower limbs during work and limits these ability of individuals to walk. As in all atherosclerotic disease, endothelial dysfunction is also present in PAD, where it plays an important role in exercise intolerance. In this disease, angiogenesis-related microRNAs (miRNAs) have reduced expression in the circulation, which possibly contributes to the observed endothelial dysfunction. However, studies shown that microRNA-126 (the main microRNA related to angiogenesis) and the expression of the enzyme nitric oxide synthase (eNOS) (responsible for the production of nitric oxide) have high expressions in the circulation after a walking session until the maximum pain of claudication in men with PAD, which may contribute to the greater blood flow observed in these individuals after performing this exercise. However, most of the studies that evaluated these questions were carried out with men. As women with PAD may have impaired walking ability and vascular function when compared to men, it is possible that they present different vasodilator responses and the aforementioned substances after walking, which needs to be investigated. Thus, this project will aim to compare the vasodilatory and angiogenic responses after performing a walking exercise in men and women with PAD and IC. Therefore, men and women with PAD, IC and age > 50 years will be studied. Thirty individuals will be recruited (15 men and 15 women), who will participate in two experimental sessions conducted in random order: walking exercise (15 sets of 2 min of walking at pain threshold HR interspersed with 2 min of passive rest) and control (Rest standing on the treadmill for the same time). In each session, specific interventions will be analyzed before and after: vascular function (basal flow and flow-mediated vasodilation - ultrasound) and miRNA-126 (gene expression), its targets (gene expression), genes of the angiogenic pathway (gene expression) and oxidative stress (protein quantification). Data will be analyzed with statistical methods appropriate to each variable. (AU)