Widjaja Sri L, Anniazi Masayu L, Artiko Bagus, Moelyo Annang G, Ahmadwirawan Mylco T
Division of Cardiology, Department of Pediatrics, Faculty of Medicine, Universitas Sebelas Maret, Surakarta, Indonesia.
Division of Endocrinology, Department of Pediatrics, Faculty of Medicine, Universitas Sebelas Maret, Surakarta, Indonesia.
Narra J. 2025 Apr;5(1):e1244. doi: 10.52225/narra.v5i1.1244. Epub 2025 Feb 11.
Several cellular markers have been identified as effective in detecting vascular remodeling recently. The reduced activity of bone morphogenetic protein receptor type-II (BMPR-II), commonly observed in Down syndrome, results in insufficient production of vascular endothelial cadherin (VE-cadherin). This, in turn, increases hypoxia-inducible factor-1α (HIF-1α) levels and leads to excessive production of caspase-3. The aim of this study was to compare the plasma levels of BMPR-II, VE-cadherin, HIF-1α, and caspase-3 between pediatric Down syndrome with and without congenital heart disease (CHD) and pulmonary hypertension (PH). This was to investigate the role of these biomarkers in the pathogenesis of PH associated or not associated with CHD. A cross-sectional study was conducted on Down syndrome children aged two months to five years at a tertiary hospital between January and December 2023. The children were classified into four groups: CHD with PH, CHD without PH, non-CHD with PH and normal heart. Plasma levels of BMPR-II, caspase-3, HIF-1α, and VE-cadherin were measured using ELISA and compared based on the presence or absence of CHD and PH using Kruskal-Wallis followed by post hoc Bonferroni tests. Elevated plasma HIF-1α levels were observed in all patients with PH, with significantly higher levels in those with CHD-PH. Elevated levels of caspase-3 were also observed among children with PH groups, with the highest levels observed in the non-CHD PH group. Plasma levels of BMPR-II and VE-cadherin were elevated in PH, with significantly higher levels in the non-CHD PH group compared to other groups.
近年来,几种细胞标志物已被确定在检测血管重塑方面有效。在唐氏综合征中常见的骨形态发生蛋白受体II型(BMPR-II)活性降低,导致血管内皮钙黏蛋白(VE-钙黏蛋白)产生不足。这反过来又会增加缺氧诱导因子-1α(HIF-1α)水平,并导致半胱天冬酶-3过度产生。本研究的目的是比较患有和未患有先天性心脏病(CHD)及肺动脉高压(PH)的小儿唐氏综合征患者血浆中BMPR-II、VE-钙黏蛋白、HIF-1α和半胱天冬酶-3的水平。这是为了研究这些生物标志物在与CHD相关或不相关的PH发病机制中的作用。2023年1月至12月,在一家三级医院对2个月至5岁的唐氏综合征儿童进行了一项横断面研究。这些儿童被分为四组:患有PH的CHD、不患有PH的CHD、患有PH的非CHD和心脏正常组。使用酶联免疫吸附测定法(ELISA)测量血浆中BMPR-II、半胱天冬酶-3、HIF-1α和VE-钙黏蛋白的水平,并使用Kruskal-Wallis检验及事后Bonferroni检验,根据是否存在CHD和PH进行比较。在所有患有PH的患者中均观察到血浆HIF-1α水平升高,其中患有CHD-PH的患者水平显著更高。在患有PH的儿童组中也观察到半胱天冬酶-3水平升高,在非CHD PH组中观察到的水平最高。在PH患者中,血浆BMPR-II和VE-钙黏蛋白水平升高,与其他组相比,非CHD PH组的水平显著更高。