a Department of Internal Medicine, Medical Faculty, Trakia University , Stara Zagora , Bulgaria.
b Department of Molecular biology, Immunology and Medical Genetics, Medical Faculty, Trakia University , Stara Zagora , Bulgaria.
Clin Exp Hypertens. 2019;41(7):662-669. doi: 10.1080/10641963.2018.1529782. Epub 2018 Oct 11.
Renin-angiotensin system (RAS) is a complex network of enzymes and peptides with the essential role in blood pressure control. The relationships between RAS components, RAS-related genetic polymorphisms and therapy response in essential hypertension (EH) were widely explored but the results were inconclusive. The aim of this study was to explore the functional role of ACE insertion/deletion (I/D) polymorphism on the systemic quantity of angiotensin-converting enzyme (ACE), its homolog - ACE2, chymase and angiotensin II in EH patients with respect to achieved therapeutic blood pressure control. Genotyping of ACE I/D polymorphism was performed among 140 patients with EH from Bulgaria. The serological analyses reveal the significant elevation of the serum quantity of all investigated enzymes in EH than normotensive controls. In addition, serum ACE2 (183.57 pg/ml; vs. 151.78 pg/ml; p = 0.02) and chymase (68.5 pg/ml; vs. 23.66 pg/ml; p = 0.034) were significantly higher in patients with uncontrolled EH than controlled EH in response to ACE-inhibitory therapy. Also, ACE I/D polymorphism showed a significant impact on the serum ACE and chymase levels. ACE quantity was the highest among carriers of DD-genotype, followed by ID and II-genotype. Contrary, chymase was in the highest quantity in II-genotype compared to ID-genotype (p = 0.025) and DD-genotype (p = 0.044). Our results suggest that insufficient blood pressure control by ACE-inhibitory therapy could be associated with elevation of serum ACE2 and chymase levels. Also, it appears that ACE I/D polymorphism may influence the circulating quantity of chymase in addition to ACE.
肾素-血管紧张素系统（RAS）是一个复杂的酶和肽网络，在血压控制中起着至关重要的作用。RAS 成分、RAS 相关遗传多态性与原发性高血压（EH）治疗反应之间的关系已被广泛探讨，但结果尚无定论。本研究旨在探讨 ACE 插入/缺失（I/D）多态性对 EH 患者系统中血管紧张素转换酶（ACE）、其同源物 ACE2、糜酶和血管紧张素 II 数量的功能作用，以及这些因素与实现治疗性血压控制的关系。在保加利亚的 140 名 EH 患者中进行了 ACE I/D 多态性基因分型。血清学分析显示，EH 患者血清中所有研究酶的数量均显著高于正常血压对照组。此外，与接受 ACE 抑制治疗后血压得到控制的 EH 患者相比，未得到控制的 EH 患者血清 ACE2（183.57 pg/ml；vs. 151.78 pg/ml；p = 0.02）和糜酶（68.5 pg/ml；vs. 23.66 pg/ml；p = 0.034）的水平显著升高。此外，ACE I/D 多态性对血清 ACE 和糜酶水平有显著影响。DD 基因型携带者的 ACE 数量最高，其次是 ID 和 II 基因型。相反，与 ID 基因型相比（p = 0.025）和 DD 基因型相比（p = 0.044），II 基因型的糜酶数量最高。我们的结果表明，ACE 抑制治疗后血压控制不足可能与血清 ACE2 和糜酶水平升高有关。此外，ACE I/D 多态性除了影响 ACE 外，似乎还会影响循环中糜酶的数量。
