Abstract
Vascular endothelial injury (VEI) is an early event of atherosclerosis, and reversing endothelial dysfunction has become a new trend in the prevention and treatment of cardiovascular diseases. Hengshun aromatic vinegar (HSAV), a traditional vinegar, has been reported to have many pharmacological activities, but its effect against VEI and the molecular mechanism are still unknown. In this study, effects of HSAV on VEI were evaluated in H2O2-induced human umbilical vein endothelial cells (HUVECs) and methionine-induced VEI in rats. Results showed that HSAV significantly increased cell viability, inhibited apoptosis, and reduced the generation of reactive oxygen species (ROS) in H2O2-induced HUVECs. Meanwhile, HSAV decreased serum homocysteine (Hcy), endothelin 1 (ET-1), and oxidized low-density lipoprotein (ox-LDL) levels, increased nitric oxide (NO) and endothelin nitric oxide synthase (eNOS) levels, ameliorated pathological changes in rats with VEI induced by methionine. In parallel, HSAV relieved oxidative stress by decreasing malondialdehyde (MDA) level and increasing superoxide dismutase (SOD), glutathione (GSH), and glutathione peroxidase (GSH-Px) levels in rats with VEI. Mechanism studies indicated that HSAV markedly downregulated the expression of protein kinase C zeta (PKCζ), and consequently regulated sirtuin 1 (Sirt1)-mediated oxidative stress signal pathway, and protein inhibitor of activated STATy (PIASy)-mediated apoptosis pathway, leading to the alleviation of oxidative stress and inhibition of apoptosis. These regulative effects of HSAV were further validated by knockdown and overexpression of PKCζ in vitro. In conclusion, HSAV showed protective effect against VEI by inhibiting PKCζ and, thereby, ameliorating oxidative stress and inhibiting apoptosis. This study not only provides guidance for the consumption of vinegar in daily life but also promotes the development of diet supplement for disease prevention.
Highlights
Coronary artery disease (CAD) is one of the major cardiovascular diseases, which has been indicated as the main leading cause of death globally [1]
Results indicated that the cell viabilities of human umbilical vein endothelial cells (HUVECs) were significantly decreased after H2O2 treatment for 2 and 4 h (Figure 1B), which was significantly decreased to 60.8% when HUVECs were treated with 200 μmol/L H2O2 for 2 h (Figure 1B)
The cell morphology gradually reappeared to normal with Hengshun aromatic vinegar (HSAV) treatment (Figure 1D). These results indicated that HSAV alleviated the injury of HUVECs induced by H2O2
Summary
Coronary artery disease (CAD) is one of the major cardiovascular diseases, which has been indicated as the main leading cause of death globally [1]. The risk factors of CAD development include genetic factors, environmental, and lifestyle. Hengshun Aromatic Vinegar Ameliorates VEI events [2, 3], which prompted the exploration of the underlying mechanism of CAD. Long-term studies have indicated that vascular endothelial injury (VEI) caused impairment of endothelial function is closely related to the occurrence and development of CAD [4,5,6]. The abnormal vasomotor contraction, increased tension, platelet adhesion, aggregation, and thrombosis caused by VEI play initiating and promoting roles in the pathogenesis of CAD [7]. Reversing endothelial dysfunction has become a new trend in prevention and treatment of CAD
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