系統性硬化症與血管疾病：揭示內皮細胞損傷的新指標

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這項研究專注於系統性硬化症（SSc）患者中血液凝固和纖維蛋白溶解途徑的變化，以及內皮細胞損傷的循環標誌物。研究發現，SSc患者的血液凝固顯著激活，而纖維蛋白溶解受到抑制。研究還指出，循環中的皮膚硫酸鹽（DS）水平增加，可能是內皮細胞損傷的新標誌。這些發現有助於理解SSc患者血管病變的機制，並可能指導未來的治療策略。

血液凝固、纖維蛋白溶解以及系統性硬化症中內皮細胞功能障礙的標誌物

Blood coagulation, fibrinolysis, and markers of endothelial dysfunction in systemic sclerosis

Marco Matucci Cerinic 1, G Valentini, G G Sorano, S D’Angelo, G Cuomo, L Fenu, S Generini, S Cinotti, M Morfini, A Pignone, S Guiducci, A Del Rosso, R Kalfin, D Das, F Marongiu
Affiliations expand
PMID: 12701039 DOI: 10.1053/sarh.2002.50011

https://pubmed.ncbi.nlm.nih.gov/12701039/

Abstract

To evaluate the coagulative/fibrinolytic cascade and the circulating markers of the endothelial injury in systemic sclerosis (SSc).

Plasma was obtained from 29 patients with SSc and tested for thrombin-antithrombin (TAT), fragments 1+2 (F1+2), dermatansulphate (DS), thrombomodulin (TM), lipoprotein (a) [Lp(a)], von Willebrand factor (vWF), tissue type plasminogen activator (tPA), plasminogen activator inhibitor (PAI), D-dimers, intercellular adhesion molecole-1 (ICAM-1), vascular cell adhesion molecule (VCAM), and E-selectin. The data were correlated with lung (forced vital capacity, diffusing lung capacity for carbon monoxide, vital capacity) and skin (skin score) involvement.

Coagulation was significantly activated (increase in F1+2, P <.001; TAT, P <.01; and Lp(a), P <.05). TM was not significantly different from controls. vWF was significantly increased (P <.01), and its supranormal multimers increased in more than 50% of patients. DS was significantly increased in diffuse cutaneous SSc (P <.01). Fibrinolysis was impaired as shown by reduced D-dimers (P <.01) and decreased levels of PAI (P < 0.01). The markers of endothelial injury were also significantly elevated. DS correlated significantly with forced vital capacity (P <.01) and forced vital capacity ratio (P <.01).

Injury to the endothelium reduces endothelial function, as suggested by impairment of fibrinolysis and activation of the coagulative pathway. The loss of the balance between fibrinolysis and coagulation contributes to vessel engulfment with fibrin and breakdown of vessel patency. The increase of circulating DS suggests that this factor may be a new marker of endothelial injury.

摘要

評估系統性硬化症（SSc）中凝血/纖溶激活途徑及血管內皮損傷的循環標誌物。

從29名SSc患者中獲取血漿，並檢測凝血酶-抗凝血酶（TAT）、碎片1+2（F1+2）、皮膚硫酸鹽（DS）、血栓調節蛋白（TM）、脂蛋白（a）[Lp(a)]、von Willebrand因子（vWF）、組織型纖溶酶原激活劑（tPA）、纖溶酶原激活劑抑制劑（PAI）、D-二聚體、細胞間粘附分子-1（ICAM-1）、血管細胞粘附分子（VCAM）和E-選擇素。數據與肺（強迫肺活量、一氧化碳擴散肺功能、肺活量）和皮膚（皮膚評分）參與程度相關聯。

凝血顯著激活（F1+2增加，P <.001; TAT，P <.01; 和Lp(a)，P <.05）。TM與對照組無顯著差異。vWF顯著增加（P <.01），超過50%的患者中其超常多聚體增加。在擴散性皮膚SSc中，DS顯著增加（P <.01）。纖溶受損，如降低的D-二聚體（P <.01）和PAI水平下降（P < 0.01）所示。血管內皮損傷的標誌物也顯著升高。DS與強迫肺活量（P <.01）和強迫肺活量比（P <.01）顯著相關。

對血管內皮的損傷降低了內皮功能，如纖溶受損和凝血途徑激活所示。纖溶與凝血之間平衡的失衡有助於血管被纖維蛋白所吞噬和血管通透性的破壞。循環DS的增加表明該因子可能是血管內皮損傷的新標誌物。