Department of Clinical Immunology and Rheumatology, Institute of Postgraduate Medical Education and Research (IPGME&R)/SSKM Hospital, 244, A. J. C. Bose Road, Kolkata, 700020, India.
ICMR-National Institute of Cholera and Enteric Diseases, P-33, CIT Rd, Subhas Sarobar Park, Phool Bagan, Beleghata, Kolkata, West Bengal, 700010, India.
Clin Exp Med. 2023 Jul;23(3):905-915. doi: 10.1007/s10238-022-00845-w. Epub 2022 Jun 25.
A comparative analysis of flow-mediated vasodilation (FMD), vasoactive angiogenic, and fibrogenic mediators between treatment-naive and treated systemic sclerosis (SSc) patients is an unmet need. (1)To assess the FMD and different pathogenic mediators in SSc patients about endothelial dysfunction. (2) To assess the proportion of circulating endothelial cells (CECs) in treatment-naïve patients. SSc patients were grouped into treatment-naïve (Group-I, n = 24) on vasodilator (Group-II, n = 10), on vasodilator + immunosuppressive (Group-III, n = 22)]. Age-sex matched healthy controls (n = 20) were included. Endothelial dysfunction (ED) was measured radiologically using FMD. Serum levels of NO, ET1, NO/ET1, sVCAM, sICAM, TGF, IL-6, and VEGF, as well as gene expressions of eNOS, iNOS, ET-1, and TGF, were measured to assess the status of ED in various study groups. CEC was measured in Group-I and HC. CEC was used as a marker to identify a key regulator of ED in SSc. FMD was significantly decreased in all SSc patients through receiving treatment. Upregulation of serum NO and ET concentrations was noted post-treatment with an unaltered NO/ET1 ratio. NO was positively correlated with FMD (r = 0.6) and negatively with TGFβ (r = - 0.5). ET-1 showed a negative correlation with TGFβ (r = - 0.5) but no significant correlation with FMD. Circulating endothelial cell (CEC) was significantly higher in Group-I (3.2%) than HC (0.8%) (p = 0.002), and it showed a good correlation with NO (r = - 0.7, p = 0.0001) and NO/ET1 (r = - 0.6, p = 0.007). Persistent ED was observed in all SSc patients irrespective of treatment. Dysbalance in NO/ET1 ratio might be the considering factor for the underlying progression of ED. Based on our findings, it may be hypothesized that reduced NO may be a contributing factor in the pathogenesis of endothelial dysfunction in SSc.
一项关于未经治疗和经治疗的系统性硬化症 (SSc) 患者之间血流介导的血管扩张 (FMD)、血管活性血管生成和纤维生成介质的对比分析是未满足的需求。(1)评估 SSc 患者内皮功能障碍的 FMD 和不同致病介质。(2)评估未经治疗的患者循环内皮细胞 (CEC) 的比例。SSc 患者分为未经治疗的患者组 (I 组，n=24)、血管扩张剂治疗组 (II 组，n=10)、血管扩张剂+免疫抑制剂治疗组 (III 组，n=22)。年龄性别匹配的健康对照组 (n=20) 包括在内。使用 FMD 进行放射学评估内皮功能障碍 (ED)。测量血清中一氧化氮 (NO)、内皮素 1 (ET1)、NO/ET1、可溶性血管细胞黏附分子 (sVCAM)、可溶性细胞间黏附分子 (sICAM)、转化生长因子 (TGF)、白细胞介素 6 (IL-6) 和血管内皮生长因子 (VEGF) 的水平，并测量 eNOS、iNOS、ET-1 和 TGF 的基因表达，以评估各组 ED 的状态。在 I 组和 HC 中测量 CEC。CEC 被用作识别 SSc 中 ED 的关键调节剂的标志物。所有 SSc 患者在接受治疗后 FMD 明显降低。NO 和 ET 浓度的上调在接受治疗后被注意到，而 NO/ET1 比值没有改变。NO 与 FMD 呈正相关(r=0.6)，与 TGFβ呈负相关(r=-0.5)。ET-1 与 TGFβ 呈负相关(r=-0.5)，但与 FMD 无显著相关性。I 组的循环内皮细胞 (CEC) 明显高于 HC(3.2% vs. 0.8%，p=0.002)，与 NO(r=-0.7，p=0.0001)和 NO/ET1(r=-0.6，p=0.007)呈良好相关性。所有 SSc 患者均存在持续的 ED，与治疗无关。NO/ET1 比值的失衡可能是 ED 潜在进展的考虑因素。根据我们的发现，可以假设减少的 NO 可能是 SSc 内皮功能障碍发病机制中的一个促成因素。
