Vascular impairment associated with diabetic condition

Diabetes mellitus (DM) is a common metabolic disease, affecting about 170 million people worldwide. DM is characterized by micro and macrovascular alterations impairing vascular homeostasis. Angiogenesis, the formation of new blood vessels from pre-existing ones, ap pears as a deregulated mechanism in DM, with distinct angiogenic patterns in different organs. The same patient can present an enhancement in microvessel density (MVD) in the kidney, and a reduction in the number of vessels in heart. This study aimed at investigating the molecular mechanisms underlying the DM related angiogenic paradox. For the analyses, C57Bl/6 mice were randomly divided into 2 groups: the control group (fed with a standard diet), and the diabetic group (fed with a high fat diet) during 12, 16 or 20 weeks. After this period, animals were euthanized and the blood was collected to assess inflammatory and biochemical markers. Kidney, left ventricle and liver were collected for western blotting analyses to evaluate the expression of specific angiogenic receptors and related pathways; or for histological analyses. Three micrometer thick tissue sections were used for histological and immunohistochemistry analysis to evaluate tissue microvessel density. Each determination was performed in at least three independent experiments. Statistical significant differences between groups were evaluated by ANOVA followed by the Bonferroni test. A difference between experimental groups was considered significant with a confidence interval of 95%, whenever p ≤ 0.05. According to the obtained results, a slight increase was observed in MVD in the kidney of HFD animals, as well as a tendency for a reduction of the neovascularization in the left ventricle. In addition, an increase in VEGFR2 phosphorylation (p-VEGFR2) was observed in kidney both over time and in HFD-fed animals. Conversely, in the left ventricle, animals fed with a HFD had a reduction in p-VEGFR2. These results were accompanied by an imbalance in several biochemical markers and in IL-1β plasmatic levels. These findings confirm the presence of the angiogenic paradox in diabetic animals. The identification of these angiogenic molecular pathways and the clarification of this paradox in DM associated with metabolic profile is the first step for development of therapeutic strategies against DM complications.