Hyperbaric oxygen therapy mitigates left ventricular remodeling, upregulates MMP-2 and VEGF, and inhibits the induction of MMP-9, TGF-β1, and TNF-α in streptozotocin-induced diabetic rat heart

Abstract

AimsHyperbaric oxygen (HBO) therapy has been widely used for the adjunctive treatment of diabetic wounds, and is currently known to influence left ventricular (LV) function. However, morphological and molecular repercussions of the HBO in the diabetic myocardium remain to be described. We aimed to investigate whether HBO therapy would mitigate adverse LV remodeling caused by streptozotocin (STZ)-induced diabetes. Main methodsSixty-day-old Male Wistar rats were divided into four groups: Control (n = 8), HBO (n = 7), STZ (n = 10), and STZ + HBO (n = 8). Diabetes was induced by a single STZ injection (60 mg/kg, i.p.). HBO treatment (100% oxygen at 2.5 atmospheres absolute, 60 min/day, 5 days/week) lasted for 5 weeks. LV morphology was evaluated using histomorphometry. Gene expression analyzes were performed for LV collagens I (Col1a1) and III (Col3a1), matrix metalloproteinases 2 (Mmp2) and 9 (Mmp9), and transforming growth factor-β1 (Tgfb1). The Immunoexpression of cardiac tumor necrosis factor-α (TNF-α) and vascular endothelial growth factor (VEGF) were also quantified. Key findingsHBO therapy prevented LV concentric remodeling, heterogeneous myocyte hypertrophy, and fibrosis in diabetic rats associated with attenuation of leukocyte infiltration. HBO therapy also increased Mmp2 gene expression, and inhibited the induction of Tgfb1 and Mmp9 mRNAs caused by diabetes, and normalized TNF-α and VEGF protein expression. SignificanceHBO therapy had protective effects for the LV structure in STZ-diabetic rats and ameliorated expression levels of genes involved in cardiac collagen turnover, as well as pro-inflammatory and pro-angiogenic signaling.