Sirtuin 1 induced VEGF-A overexpression along with increased pericyte coverage and basement membrane alterations in...

Sirt1 is of main importance in vascular homeostasis maintenance and in the protection of microcirculatory function during pathology. However, the exact mechanisms underlying the protective effects of Sirt1 on retinal vasculature are still not fully understood. Here, we analyse the effects of Sirt1 overexpression in the retina of transgenic mice. Mice retinas were studied by means of PCR, Western blot and immunohistochemistry to assess the expression of Sirt1, VEGF-A, and the PDGF-B/PDGFR-β pathway. Retinal vasculature was deeply analysed by immunohistochemistry, trypsin digestion, and transmission electron microscopy. Our results showed that Sirt1-tg mice exhibited a moderate retinal Sirt1 overexpression throughout the retinal parenchyma, mainly at the nuclei of vascular retinal cells. This Sirt1 overexpression led to an increased expression of retinal VEGF-A. In addition, our results suggested that the expected VEGF-driven angiogenesis was prevented in Sirt1-tg mice retinas by two vessel stabilization mechanisms: increased pericyte coverage, and focal increased collagen IV deposition in blood vessel basement membrane. Altogether, our findings may indicate a possible role for Sirt1 in modulating VEGF angiogenic effects, potentially being associated with changes in pericyte coverage and basement membrane protein deposition in retinal blood vessels.