Abstract
BackgroundNitric oxide (NO) is the most powerful vasodilator that inhibits leukocyte adhesion, platelet aggregation, and vascular smooth muscle cell proliferation. However, excessive NO can cause lipid peroxidation and direct endothelial cell damage. Therefore, investigation of the role of NO in artherosclerosis development is important. Wen-Xin Decoction (WXD) has been shown to relieve myocardial ischemia reperfusion injury and prevent leukocyte adhesion and invasion; in addition, it can accelerate angiogenesis and prevent platelet activation and aggregation. In this study, we focused on the NO pathway to further clarify the protective effects of WXD on the vascular endothelium in rat models of artherosclerosis.MethodsWistar rats were randomly divided into a normal group (n = 10) and a model group (n = 75). Rat models of atherosclerosis were generated by intraperitoneal vitamin D3 (3 months) injections and administration of a high-fat diet (3 months with vitamin D3 and 2 months alone). The model rats were randomly divided into five groups (n = 15 each): model (saline), atorvastatin (4.8 mg/kg/d atorvastatin), high-dose WXD (9 g/kg/d), medium-dose WXD (4.5 g/kg/d), and low-dose WXD (2.25 g/kg/d) groups. Each group received continuous drug or saline administration (suspended liquid gavage) for 30 days, following which all animals were sacrificed. The ultrastructure and histopathological changes of vascular endothelial cells and the expression of PI3K/AKT/eNOS and iNOS in the thoracic aorta tissue were analyzed.ResultsWXD increased NO levels, modulated the NO/ET-1 ratio, and promoted repair of the injured vascular endothelium in a dose-dependent manner. At a high dose, WXD regulated the NO/ET-1 ratio as effectively as atorvastatin; furthermore, it increased NO levels within the physiological range to prevent endothelial damage caused by excessive NO expression. Real-time polymerase chain reaction and Western blot analysis showed that WXD significantly upregulated the mRNA and protein expressions of PI3K, AKT, and eNOS mRNA and significantly increased AKT and eNOS phosphorylation.ConclusionsOur results suggest that WXD protects and maintains the integrity of the vascular endothelium by activating the PI3K/AKT/eNOS pathway, decreasing iNOS expression, and promoting the release of physiological NO levels.
Highlights
Nitric oxide (NO) is the most powerful vasodilator that inhibits leukocyte adhesion, platelet aggregation, and vascular smooth muscle cell proliferation
Studies have been trying to interpret this disease by investigating various factors, including “endothelial injury” [2], “lipid infiltration,” “inflammatory response” [3], and “thrombosis.” it is clear that disruption of the integrity of the vascular endothelium and its dysfunction are part of the initial factors causing AS [4,5,6,7,8]
We focused on the NO pathway to further clarify the protective effects of Wen-Xin Decoction (WXD) on the vascular endothelium in rat models of AS
Summary
Nitric oxide (NO) is the most powerful vasodilator that inhibits leukocyte adhesion, platelet aggregation, and vascular smooth muscle cell proliferation. We focused on the NO pathway to further clarify the protective effects of WXD on the vascular endothelium in rat models of artherosclerosis. Studies have shown that the increase in morbidity and mortality in low- and middle-income countries will increase the number of worldwide deaths from cardiovascular disease to 2330 million by 2030 [1]. Studies have been trying to interpret this disease by investigating various factors, including “endothelial injury” [2], “lipid infiltration,” “inflammatory response” [3], and “thrombosis.” it is clear that disruption of the integrity of the vascular endothelium and its dysfunction are part of the initial factors causing AS [4,5,6,7,8]. The protection of endothelial function is significant for the prevention and treatment of AS
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