Authored by Douglas Reis Abdalla*
Abstract
In order to understand the relationships of the influence of physical activity in the angiogenesis process, this review aims to recruit in the last ten years the evidence on this topic. The study data collection took place between February 20 and March 20, 2020. The electronic databases used to search the articles was PubMed (National Library of Medicine and National Institutes of Health). We used the keywords: angiogenesis, angiogenic effect, vascular endothelial growth factor (VEGF), physical activity, physical exercise, exercise and training, in the English languages, accompanied by the expression AND and selected through DeCS (Descriptors in Health Sciences). The performance of physical activity, (Figure 2), whether aerobic or resisted with load, promotes in the body an increase in pro-angiogenic factors such as: IL-6, Ang 1 and 2, VEGF, PDGF, FGF and stimulation of their receptors, being, respectively: IL -6Ra, TIE-2, VEGFR-1 and 2, PDGFR, FGFR. Higher levels of Adropine also encourage the expression of VEGFR-2. The activation of IL-6Ra, VEGFR-1 and 2 receptors elevates, together with increased expression of miR-126, a small fragment of non-coded RNA, the enzyme PI3k (Phosphoinositide 3-kinase). This increased enzyme induces the expression of protein Kinase B (Akt) which plays a fundamental role in cell metabolism via the mTOR pathway. We will then have the formation of MMP-2, MMP-9, VEGF, CD31 and HIF-1α, the latter being directly stimulated by the increase in NO. In this way, those responsible for proliferation, migration, survival and cell permeability will be present, necessary for improvements in the levels of angiogenesis to occur. It was possible to conclude that the physical activity induced in both experimental and human models favored the process of angiogenesis in organisms by increasing pro factors and decreasing anti-angiogenic factors, regardless of preexisting comorbidities and previous sedentary lifestyle.
Keywords: Physical activity; Exercise; Angiogenesis; Vascular Endothelial Growth Factor
Introduction
The word “angiogenesis” was derived from the Greek where “angio” means blood vessel and “genesis” means production or birth, together they refer to the generation of blood vessel within the body. Historically, the term angiogenesis was first used to describe the growth of endothelial shoots from pre-existing postcapillary veins. Over time, this term has been used to denote the process of growth and remodeling of the primitive network of a vascular complex [1]. The vascular system is responsible for the supply of nutrients and oxygen in an organism. New blood vessel formation or neovascularization is divided into two components like vasculogenesis and angiogenesis. The vasculogenesis process is the formation of blood vessels from hemangioblasts that differentiate into mature blood and endothelial cells [2]. Angiogenesis is the process of forming new blood vessels from a pre-existing vascular network, by capillary sprouting [3]. Vasculogenesis ascends the heart and the first primitive vascular plexus within the embryo and in the surrounding membranes, considering that angiogenesis is responsible for the remodeling and expansion of this network. During this process, mature endothelial cells are divided and incorporated into new capillaries. The signaling of vascular endothelial growth factors (VEGF) is necessary for the complete performance of vasculogenesis and angiogenesis [2,4].
The health benefits of regular physical activity are present in several chronic diseases, including cardiovascular disease, diabetes, hypertension and cancer [5-8]. However, physical inactivity is a risk factor for several pathological conditions, including obesity, hypertension, atherosclerosis and cancer [9-11]. Physical training is known to profoundly alter the morphology of blood vessels along the arterial tree [12-14]. Exercise provides increases related to the quantity (angiogenesis) and the diameter (arteriogenesis) of the arterial blood vessels in the skeletal muscle and in the myocardium. These changes in the architecture of the vascular tree are probably associated with functional changes and improved blood flow to the organ [15-18]. Changes in vascular morphology induced by physical exercise in healthy individuals [15,16] are extremely dependent on the size of the initial vessel. A greater number of vessels in response to training, angiogenesis, appears to occur on the level of very small capillaries and arterioles (<40 μm in diameter), but not in large arteries. The increase in capillary density occurs just after the beginning of the exercise and is transient. A similar pattern was observed in very small arterioles (<20 μm in diameter) and slightly in larger arterioles (20-40 μm in diameter) an increase in the number was also observed [19].
The molecular mechanisms underlying exercise-induced angiogenesis are not fully understood. It has been suggested that growth factors such as vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF) and angiopoietins (ANG) as well as their corresponding receptors are involved. In addition, the proteases necessary for the degradation of the capillary basement membrane such as matrix metalloproteinases (MMPs), urokinase, tissue plasminogen activator probably contribute to the mechanism of the emergence of angiogenesis [16,20,21]. Interestingly, some of these proteases appear to allow and/or facilitate the mobilization of endothelial progenitor cells (EPCs) from the bone marrow. It has become apparent that exercise can increase the number of circulating EPCs in animals and humans, and these cells are known to have a large capacity for neovascularization, a process that appears to be critically dependent on the protease cathepsin L [22,23]. In order to understand the relationships of the influence of physical activity in the angiogenesis process, this review aims to recruit in the last ten years the evidence on this topic.
Methodology
In the present study, an integrative review was conducted, which consists of research that allows the evaluation, synthesis and knowledge about a phenomenon from evidence, aiming to produce an overview of complex concepts, theories or relevant health problems from studies pre-existing, enabling the intervention proposal [24,25]. For the selection of articles, 6 methodological steps were carried out, namely: 1. elaboration of the guiding question or research hypothesis, that is, the problem was identified, the search engine and the keywords or keywords were presented; 2. establishment of the inclusion and exclusion criteria of the articles to be selected to compose the sample; 3. exploratory reading of the titles and abstracts of the articles for pre-selection; 4. analytical reading of the articles in order to compile, analyze and categorize the information; 5. interpretation of results. 6. synthesis followed by the presentation of the identified results, which permeate the guiding question [26].
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