Effects of Antioxidant Tempol on Systematic Inflammation and Endothelial Apoptosis in Emphysematous Rats Exposed to Intermittent Hypoxia

Abstract

PurposeObstructive sleep apnea and chronic obstructive pulmonary disease are independent risk factors of cardiovascular disease (CVD), and their coexistence is known as overlap syndrome (OS). Endothelial dysfunction is the initial stage of CVD; however, underlying mechanisms linking OS and CVD are not well understood. The aim of this study was to explore whether OS can lead to more severe inflammation and endothelial apoptosis by promoting endothelial dysfunction, and to assess the intervention effects of antioxidant tempol.Materials and MethodsMale Wistar rats (n=66) were exposed to normal oxygen [normal control (NC) group], intermittent hypoxia (IH group), cigarette smoke (CH group), as well as cigarette smoke and IH (OS group). Tempol intervention was assessed in OS group treated with tempol (OST group) or NaCl (OSN group). After an 8-week challenge, lung tissues, serum, and fresh blood were harvested for analysis of endothelial markers and apoptosis.ResultsThe levels of intracellular adhesion molecule-1, vascular cellular adhesion molecule-1, and apoptosis in circulating epithelial cells were the highest in OS group and the lowest in NC group. These levels were all greater in IH group than in CH group, and were lower in OST group than in OS and OSN groups (all p<0.001).ConclusionSynergistic effects of IH with cigarette smoke-induced emphysema produce a greater inflammatory status and endothelial apoptosis. OS-related inflammation and endothelial cell apoptosis may play important roles in promoting cardiovascular dysfunction, and antioxidant tempol could achieve a partial protective effect.

Neuropeptide Y: An Update on the Mechanism Underlying Chronic Intermittent Hypoxia-Induced Endothelial Dysfunction

“…A previous study reported that circulating endothelial cell apoptosis is an indicator of vascular injury in vitro (Feng et al, 2012), and an increasing number of studies show that chronic IH caused by oxidative stress can induce endothelial cell apoptosis, lead to loss of endothelial integrity, aggravate VE damage, promote the expression of redox-sensitive genes and adhesion molecules, and lead to the progression of hypoxiainduced cardiovascular diseases (Liu et al, 2018;Xiao et al, 2019). Zhao et al (2018) found that IH-and cigarette smokeinduced emphysema can synergistically produce a greater inflammatory response and endothelial cell apoptosis in an animal model of OSAS and chronic obstructive pulmonary disease. They also showed that use of the antioxidant Tempol could antagonize these effects, as the density of apoptotic endothelial cells in OSAS patients was higher than that in non-OSAS patients.…”