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研究高血压患者血管重构的血清水平动力学,包括在伴 2 型糖尿病患者中,进行为期 12 个月的培哚普利 A 治疗。

To study the dynamics of serum levels of vascular remodeling in patients with hypertension, including in combination with type 2 diabetes mellitus during 12‑month therapy with perindopril A.

机构信息

I.M. Sechenov First Moscow Medical University (Sechenov University), Moscow.

出版信息

Kardiologiia. 2022 Jan 31;62(1):24-31. doi: 10.18087/cardio.2022.1.n1890.

DOI:10.18087/cardio.2022.1.n1890
PMID:35168530
Abstract

Aim      To study the dynamics of serum markers for vascular remodeling in patients with arterial hypertension (AH), including AH associated with type 2 diabetes mellitus (DM2) during the 12-month treatment with the angiotensin-converting enzyme (ACE) inhibitor, perindopril A.Material and methods  The study included patients with grade 1-2 AH with or without type 2 DM (30 and 32, respectively). Perindopril A 10 mg/day was administered for the outpatient correction of previous, ineffective antihypertensive therapy. The following biomarkers were measured for all patients at baseline and at 12 months: matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), E-selectin, endothelin 1, transforming growth factor β-1 (TGF-β1), and von Willebrand factor (WF). Laboratory tests were performed with enzyme immunoassay.Results After 12 months of the perindopril A (perindopril arginine) 10 mg/day treatment, both groups achieved the goal blood pressure. Evaluation of biomarker dynamics during the perindopril A treatment showed significant decreases in MMP-9, TIMP-1, and endothelin 1 in the AH group; then the level of TIMP-1 returned to normal values (р<0.05). In the AH+DM2 group, the MMP-9 concentration was significantly decreased (р<0.05); the other values did not show any significant differences. In both groups, MMP-9 was significantly decreased (28.6 % (р=0.01) in group 1 and 33.2 % (р=0.00) in group 2. Notably, in none of these groups, did this index reach normal values. Also, there were no significant differences in this index between the groups (р=0.66). It should be noted that the decreases in TIMP-1 were significantly different between the groups (р=0.001). Thus, this biomarker did not significantly decrease in patients with AH and DM2 (р=0.26) whereas in group 1 (AH without DM2), the level of TIMP-1 decreased by 39.3 % and reached the normal range (р=0.005).Conclusion      Concentrations of biomarkers were decreased in both groups. However, in the AH group, there were statistically significant decreases in the markers that reflect processes of fibrosis and vasoconstriction. At the same time in the AH+DM2 group, there was no significant dynamics of the biomarkers, which was most likely due to more pronounced damage of blood vessels. However, the decrease in MMP-9 may indicate an alleviation of fibrotic processes in arterial walls. These results allow a conclusion that the long-term treatment with the ACE inhibitor, perindopril A, may reverse remodeling of the vascular changes that are called "early vascular ageing".r aging".

摘要

目的

研究血管重塑血清标志物在动脉高血压(AH)患者中的动态变化,包括与 2 型糖尿病(DM2)相关的 AH,在使用血管紧张素转换酶(ACE)抑制剂培哚普利治疗 12 个月期间。

材料和方法

本研究纳入了 1 级-2 级 AH 患者,无论是否合并 2 型 DM(分别为 30 例和 32 例)。培哚普利 A 10mg/天用于门诊调整之前无效的降压治疗。所有患者在基线和 12 个月时测量以下生物标志物:基质金属蛋白酶-9(MMP-9)、金属蛋白酶组织抑制剂-1(TIMP-1)、E-选择素、内皮素 1、转化生长因子-β1(TGF-β1)和血管性血友病因子(vWF)。采用酶联免疫吸附法进行实验室检查。

结果

在培哚普利 A(精氨酸培哚普利)10mg/天治疗 12 个月后,两组均达到目标血压。在培哚普利 A 治疗期间生物标志物动态变化的评估显示,AH 组 MMP-9、TIMP-1 和内皮素 1 显著降低;然后 TIMP-1 水平恢复正常(p<0.05)。在 AH+DM2 组,MMP-9 浓度显著降低(p<0.05);其他值没有显示出任何显著差异。在两组中,MMP-9 均显著降低(第 1 组降低 28.6%(p=0.01),第 2 组降低 33.2%(p=0.00)。值得注意的是,这些组中均未达到该指数的正常范围。此外,两组之间该指数无显著差异(p=0.66)。应注意的是,TIMP-1 的降低在两组之间有显著差异(p=0.001)。因此,在患有 AH 和 DM2 的患者中,TIMP-1 水平没有显著降低(p=0.26),而在第 1 组(无 DM2 的 AH)中,TIMP-1 水平降低了 39.3%并达到正常范围(p=0.005)。

结论

两组生物标志物浓度均降低。然而,在 AH 组,反映纤维化和血管收缩过程的标志物有统计学意义的降低。同时,在 AH+DM2 组,生物标志物没有明显的动态变化,这很可能是由于血管损伤更明显。然而,MMP-9 的减少可能表明动脉壁纤维化过程的缓解。这些结果表明,长期使用 ACE 抑制剂培哚普利可能逆转称为“早期血管老化”的血管变化的重塑。

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