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儿童镰状细胞病患者 TGF-β1 水平与溶血、炎症和组织重塑标志物的相关性研究。

Associations between TGF-1 Levels and Markers of Hemolysis, Inflammation, and Tissue Remodeling in Pediatric Sickle Cell Patients.

机构信息

Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, 40.296-710 Salvador, Brazil.

Universidade Federal da Bahia, 40.170-110 Salvador, Brazil.

出版信息

Mediators Inflamm. 2021 Mar 13;2021:4651891. doi: 10.1155/2021/4651891. eCollection 2021.

Abstract

Transforming growth factor beta (TGF-) is a cytokine with important involvement in biological processes related to the pathogenesis of sickle cell disease (SCD), including endothelial and vascular dysfunction, inflammation, and hematopoietic homeostasis. This study is aimed at investigating associations between levels of TGF-1 and classical laboratory biomarkers and inflammatory mediators, as well as the tissue inhibitor of metalloproteases-1 (TIMP-1) and matrix metalloproteinase-9 (MMP-9), in pediatric patients ( = 123) with SCD in steady state: 84 with sickle cell anemia (HbSS) and 39 with hemoglobin SC disease (HbSC). A healthy control (HC) group of 59 individuals was also included. Hematological and biochemical analyses were carried out using electronic methods. TGF-1, TIMP-1, and MMP-9 plasma quantifications were performed by ELISA. TGF-1 plasma levels were higher in HbSS individuals than in HbSC and HC. In individuals with HbSS, TGF-1 levels were positively correlated with red blood cells, hemoglobin, hematocrit, platelets, and TIMP-1. In addition, HbSS individuals with TGF-1 levels above the median (≥72.29 ng/mL) also presented increased monocyte counts and decreased albumin levels. In patients with HbSC, TGF-1 levels were positively correlated with leukocytes, eosinophils, lymphocytes, monocytes, and platelets, as well as levels of TIMP-1, VLDL-C, triglycerides, heme, and AST. Additionally, HbSC individuals with TGF-1 levels above the median (≥47.80 ng/mL) presented increased leukocyte and platelet counts, as well as increased levels of triglycerides, VLDL-C, MMP-9, and TIMP-1, and decreased HDL-C. Our findings suggest that TGF-1 may play important roles in vascular remodeling, vasculopathy, angiogenesis, and inflammation in pediatric patients with SCD.

摘要

转化生长因子-β(TGF-β)是一种细胞因子,在与镰状细胞病(SCD)发病机制相关的生物学过程中具有重要作用,包括内皮和血管功能障碍、炎症和造血稳态。本研究旨在研究稳定期儿科 SCD 患者(n=123)TGF-β1 与经典实验室生物标志物和炎症介质以及组织金属蛋白酶抑制剂-1(TIMP-1)和基质金属蛋白酶-9(MMP-9)之间的关联:84 例为镰状细胞贫血(HbSS),39 例为血红蛋白 SC 病(HbSC)。还纳入了 59 名健康对照(HC)个体。使用电子方法进行血液学和生化分析。通过 ELISA 法检测 TGF-β1、TIMP-1 和 MMP-9 血浆定量。HbSS 个体的 TGF-β1 血浆水平高于 HbSC 和 HC。在 HbSS 个体中,TGF-β1 水平与红细胞、血红蛋白、血细胞比容、血小板和 TIMP-1 呈正相关。此外,TGF-β1 水平高于中位数(≥72.29ng/ml)的 HbSS 个体也表现出单核细胞计数增加和白蛋白水平降低。在 HbSC 患者中,TGF-β1 水平与白细胞、嗜酸性粒细胞、淋巴细胞、单核细胞和血小板以及 TIMP-1、VLDL-C、甘油三酯、血红素和 AST 呈正相关。此外,TGF-β1 水平高于中位数(≥47.80ng/ml)的 HbSC 个体白细胞和血小板计数增加,甘油三酯、VLDL-C、MMP-9 和 TIMP-1 水平增加,HDL-C 水平降低。我们的研究结果表明,TGF-β1 可能在 SCD 儿科患者的血管重塑、血管病变、血管生成和炎症中发挥重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10bb/7984885/3952a7367cff/MI2021-4651891.001.jpg

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