2-hydroxybenzylamine(2-HOBA)curbs the pathogenesis of aging-associated atherosclerosis / 中华老年医学杂志

ABSTRACT

Objective:To explore the effects of different concentrations of 2-hydroxybenzylamine(2-HOBA)on atherosclerosis and vascular smooth muscle cell senescence and the underlying mechanisms.Methods:Fourteen apolipoprotein E-deficient(ApoE-/-)mice were used to establish an atherosclerosis model and were divided into two groups(n=7)using the random number method: a high-fat diet(HD)group and a high-fat diet plus 2-HOBA(1 mg/ml)(HD+ HOBA)group.Pulse wave velocity was used to assess vascular stiffness and a treadmill was used to assess exercise endurance.Oil Red O staining was used to detect the size and number of atherosclerotic plaques.Masson staining was used to detect the morphology of collagen fibers and elastic fibers in the plaque, the size of the necrotic core area of the plaque, and the thickness of the fibrous cap.Mouse smooth muscle cells were treated with different concentrations of 2-HOBA(100 μmol/L, 250 μmol/L and 500 μmol/L)to establish an H 2O 2-induced senescence model.Senescence-associated β-galactosidase staining was used to detect cell senescence.Real-time quantitative polymerase chain reaction(RT-qPCR)was used to detect the mRNA expression levels of senescence-related secretory phenotype factors, and Western blot was used to detect the expression levels of senescence-related signaling proteins. Results:Compared with the HD group, the HD+ HOBA group showed that the area and number of aortic atherosclerotic plaques were decreased, and the atherosclerotic plaques were stabilized.In addition, compared with the HD group, vascular stiffness in the HD+ 2-HOBA group decreased by 26%(2.59±0.32 mm/ms vs.3.50±0.28 mm/ms), with a statistically significant difference( P<0.01), and exercise endurance increased by 62%[(143.74±24.25)m vs.(233.50±30.21)m, P<0.01], suggesting that 2-HOBA was able to improve aortic vascular stiffness and exercise endurance in mice.2-HOBA ameliorated H 2O 2-induced vascular smooth muscle cell senescence and decreased the mRNA levels of H 2O 2-induced senescence-associated secretory phenotype factors such as interleukin-1β, interleukin-6, tumor necrosis factor-α and monocyte chemoattractant protein-1.Meanwhile, 2-HOBA also inhibited the expression of p53 and p21, the key signaling factors of senescence. Conclusions:2-HOBA suppresses the development and progression of atherosclerosis through inhibiting oxidative stress-related p53/p21 signaling activation and ameliorating vascular smooth muscle cell senescence and the aging-related inflammatory phenotype.