Hmox1 Deficiency Sensitizes Mice to Peroxynitrite Formation and Diabetic Glomerular Microvascular Injuries

Objective. indirect evidence suggests a role for heme oxygenase-1 (ho-1) in limiting diabetic vasculopathy. the goal of this study was to assess the role of ho-1 in the development of microvascular lesions within glomeruli during diabetes mellitus using a mouse model with specific alteration of the hmox1 gene. approach and results. the effects of hmox1 haploinsufficiency were studied as a means of assessing the intrinsic contribution of ho-1 in the development of renal microvascular lesions during diabetes. renal function and histology were analyzed 10 weeks after diabetes induction with streptozotocin. diabetic hmox1+/- mice showed higher levels of albuminuria and blood urea compared to their wild-type diabetic littermates. more severe glomerular microvascular lesions were also observed in the diabetic hmox1+/- mice. this was associated with a renal increase in the expression of the oxidative stress marker,nitrotyrosine. conclusions. genetic hmox1 partial deficiency is sufficient to sensitize mice to the development of diabetic glomerular microvascular lesions. ho-1 exerts antioxidant effects in the kidney during diabetes mellitus. these have protective effects on the development of glomerular endothelial injury. © 2017 olivia lenoir et al.