高血压患者主动脉组织和外周血单个核细胞烟酰胺腺嘌呤二核苷酸水平变化及其与血管功能的关系

Nicotinamide adenine dinucleotide (NAD+) levels in aorta and peripheral blood mononuclear cells in patients with hypertension and its relationship with vascular function: a clinical study

  • 摘要: 目的 探讨高血压患者主动脉组织和外周血单个核细胞(PBMCs)中烟酰胺腺嘌呤二核苷酸(NAD+)水平的变化及其与血压和血管功能的关系。方法 收集3例高血压患者和3名健康对照者的主动脉组织,利用液相色谱-质谱联用技术测定主动脉组织NAD+浓度;招募30例原发性高血压患者和30名健康受试者,测定PBMCs中NAD+浓度;采用肱-踝动脉脉搏波传导速度(baPWV)和血流介导的血管舒张功能(FMD)评价血管功能。比较原发性高血压患者和健康对照组主动脉组织和PBMCs中的NAD+浓度。采用Pearson相关分析和多因素logistic回归分析方法分析PBMCs中NAD+水平与血压、baPWV、FMD的相关性。结果 与健康对照组比较,高血压患者主动脉组织NAD+水平降低(12.71±3.62)比(31.28±6.69)pmol/mg,t=4.228,P=0.013;高血压患者PBMCs中NAD+浓度也降低(7.76±5.43)比(16.15±8.70)pmol/mg,t=2.752,P=0.009,同时伴有baPWV增加(1 653.00±271.80)比(1 279.00±196.80)cm/s,t=6.114,P<0.001和FMD降低(5.43±2.41)%比(7.04±1.95)%,t=1.974,P=0.004。线性相关分析显示,NAD+与收缩压(r=-0.508,P<0.001)、舒张压(r=-0.460,P<0.001)、baPWV(r=-0.559,P<0.001)呈负相关,与FMD(r=0.528,P<0.001)呈正相关。多因素logistic回归分析显示,PBMCs中NAD+水平与FMD(OR=0.877,95%CI 0.799~0.963,P=0.006)、baPWV(OR=0.906,95%CI 0.836~0.982,P=0.017)和收缩压(OR=0.823,95%CI 0.733~0.924,P=0.001)及舒张压(OR=0.878,95%CI 0.792~0.973,P=0.013)均独立相关。结论 高血压患者主动脉组织和PBMCs中NAD+水平降低,且PBMCs中NAD+水平与高血压相关血管功能障碍密切相关。

     

    Abstract: Objective To explore the change of nicotinamide adenine dinucleotide(NAD+) in aorta and peripheral blood mononuclear cells(PBMCs) in hypertensive patients and its relationship with blood pressure and vascular function. Methods Aortic tissues were collected from 3 patients with hypertension and 3 healthy controls. The NAD+ level in aorta was determined by high performance liquid chromatography-mass spectrometry(HPLC-MS). Thirty patients with essential hypertension and 30 healthy subjects were recruited. The concentration of NAD+ in PBMCs was measured. Brachial-ankle pulse wave velocity(baPWV) and flow-mediated dilation(FMD) were used to evaluate vascular function. The concentrations of NAD+ in aortic tissue and PBMCs between patients with essential hypertension and healthy controls were compared. Pearson correlation analysis and multivariate logistic regression analysis were used to analyze the correlation between NAD+ level in PBMCs and blood pressure, baPWV and FMD. Results Compared with the control group, the NAD+ level in aortic tissue was significantly decreased in the hypertensive group (12.71±3.62) vs(31.28±6.69) pmol/mg tissue, t=4.228, P=0.013. The concentration of NAD+ in PBMCs of hypertensive patients was also significantly lower (7.76±5.43) vs(16.15±8.70) pmol/mg protein, t=2.752, P=0.009, accompanied by increased baPWV (1 653.00±271.80) vs(1 279.00±196.80) cm/s, t=6.114, P<0.001 and decreased FMD (5.43±2.41)% vs(7.04±1.95)%, t=1.974, P=0.004. Linear correlation analysis showed that NAD+ in PBMCs was negatively correlated with systolic blood pressure(r=-0.508, P<0.001), diastolic blood pressure(r=-0.460, P<0.001), baPWV(r=-0.559, P<0.001) and positively correlated with FMD(r=0.528, P<0.001). Multivariate logistic regression analysis showed that NAD+ levels in PBMCs were independently correlated with FMD(OR=0.877, 95%CI 0.799-0.963, P=0.006), baPWV(OR=0.906, 95%CI 0.836-0.982, P=0.017), systolic blood pressure(OR=0.823, 95%CI 0.733-0.924, P=0.001) and diastolic blood pressure(OR=0.878, 95%CI 0.792-0.973, P=0.013). Conclusion NAD+ levels in the aorta and PBMCs are decreased in hypertensive patients, and the NAD+ level in PBMCs is closely related to hypertensive vascular dysfunction.

     

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