Loss of Gucy1a3 Causes Poor Post-Stroke Recovery by Reducing Angiogenesis Via the HIF-1α/VEGFA Signaling Pathway in Mice
Abstract Ischemic stroke is a common and debilitating disease that can cause permanent neurological damage. Gucy1a3, which encodes the α1 subunit of soluble guanylyl cyclase, has been reported to be associated with functional recovery after ischemic stroke. However, the mechanism is still not well understood. In the present study, we investigated the effects of Gucy1a3 on (i) post-stroke recovery; (ii) vascular endothelial growth factor A (VEGFA) and hypoxia inducible factor 1 alpha (HIF-1α) expression; and (iii) angiogenesis after ischemic stroke. A permanent middle cerebral artery occlusion (pMCAO) model was established using wild-type and Gucy1a3 knockout C57BL/6J male mice. Neurological deficits, infarct volume, microvascular density, and VEGFA and HIF-1α expression levels of mice were evaluated. Our results suggest that loss of Gucy1a3 increased the infarct volume and aggravated neurological deficits after pMCAO. In addition, the Gucy1a3 knockout brains exhibited significantly lower microvessel densities and VEGFA and HIF-1α expression levels than the wild-type brains at 96 hours post-pMCAO. The study shows that the expression of GUCY1A3 after ischemic stroke may play a substantial role in neurological function recovery and is related to angiogenesis in the peri-infarct region. The beneficial effects of GUCY1A3 might be mediated through the HIF-1α/VEGFA signaling pathway.