Department of Medicine, Discipline of Nephrology, Federal University of São Paulo, São Paulo, Brazil.
Center of Biological Sciences and Health, Mackenzie Presbyterian University, São Paulo, Brazil.
Hypertens Res. 2023 Jun;46(6):1558-1569. doi: 10.1038/s41440-023-01240-y. Epub 2023 Mar 24.
This study aimed to evaluate the enzymatic activity of the angiotensin-converting enzyme (ACE) in children and adolescents to investigate their relationship with dyslipidemia and other cardiometabolic alterations. Anthropometric measurements, blood pressure (BP), and fasting lipid concentrations were taken from 360 subjects. Categorization was done according to the levels of each lipoprotein (total cholesterol, triglycerides (TG), LDL-C, HDL-C, and non-HDL-C) into three groups: normolipidemic (NL), borderline (BL), and dyslipidemic (DL). Enzymatic activity in urine was measured using the substrates Z-FHL-OH and hippuryl-HL-OH (h-HL-OH) and the ACE activity ratio (Z-FHL-OH/h-HL-OH) was calculated. Dyslipidemic levels of HDL-C, TG, and LDL-C were observed in 23%, 9%, and 3% of the participants, respectively, and were more frequent in obese children (Chi-square, p < 0.001). ACE activity ratio was augmented in BL(HDL-C) when compared to NL(HDL-C) (5.06 vs. 2.39, p < 0.01), in DL(LDL-C) in comparison to BL(LDL-C) and NL(LDL-C) (8.7 vs. 1.8 vs. 3.0, p < 0.01), and in DL(non-HDL-C) than in BL(non-HDL-C) and in NL(non-HDL-C) (6.3 vs. 2.1 vs. 2.9, p = 0.02). The groups with impaired HDL-C and TG levels presented an increased diastolic BP percentile, and a higher systolic BP percentile was observed in BL(TG) and DL(TG). The carotidal-femoral pulse wave velocity (cfPWV) was higher in the groups with DL levels of TG and LDL-C than in NL groups. Hypertriglyceridemia was associated with higher cfPWV. No direct impact of the ACE activity on BP values was observed in this cohort, however, there was an association between hyperlipidemia and ACE upregulation which can trigger mechanisms driving to early onset of hypertension and cardiovascular disease. Graphical abstract exemplifying the cohort, categorization of subjects into the groups NL normolipidemic, BL borderline, DL dyslipidemic, methods, and main findings. Pediatric dyslipidemia was consistent with dyslipidemia secondary to obesity (DSO), associated with higher urinary angiotensin-converting enzyme (ACE) activity ratio, BP blood pressure values, and carotidal-femoral pulse wave velocity (cfPWV).
本研究旨在评估儿童和青少年血管紧张素转换酶(ACE)的酶活性,以研究其与血脂异常和其他心血管代谢改变的关系。对 360 名受试者进行了人体测量学测量、血压(BP)和空腹血脂浓度检测。根据脂蛋白(总胆固醇、甘油三酯(TG)、LDL-C、HDL-C 和非 HDL-C)水平对其进行分类,分为三组:正常血脂(NL)、边缘(BL)和血脂异常(DL)。使用 Z-FHL-OH 和 hippuryl-HL-OH(h-HL-OH)作为底物测量尿液中的酶活性,并计算 ACE 活性比值(Z-FHL-OH/h-HL-OH)。研究参与者中分别有 23%、9%和 3%出现 HDL-C、TG 和 LDL-C 血脂异常水平,且肥胖儿童中更为常见(卡方检验,p<0.001)。与 NL(HDL-C)相比,BL(HDL-C)的 ACE 活性比值升高(5.06 比 2.39,p<0.01),与 BL(LDL-C)和 NL(LDL-C)相比,DL(LDL-C)的 ACE 活性比值升高(8.7 比 1.8 比 3.0,p<0.01),与 BL(非 HDL-C)和 NL(非 HDL-C)相比,DL(非 HDL-C)的 ACE 活性比值升高(6.3 比 2.1 比 2.9,p=0.02)。HDL-C 和 TG 水平受损的组舒张压百分位较高,BL(TG)和 DL(TG)组收缩压百分位较高。与 NL 组相比,TG 和 LDL-C 水平异常的 DL 组的颈股脉搏波速度(cfPWV)更高。高甘油三酯血症与较高的 cfPWV 相关。在该队列中,ACE 活性对血压值没有直接影响,但血脂异常与 ACE 上调之间存在关联,ACE 上调可能引发导致高血压和心血管疾病早期发病的机制。图表说明了队列、将受试者分为 NL 正常血脂、BL 边缘、DL 血脂异常组、方法和主要发现。儿科血脂异常与肥胖相关的血脂异常(DSO)一致,与较高的尿血管紧张素转换酶(ACE)活性比值、血压值和颈股脉搏波速度(cfPWV)相关。