Ko Junsuk, Noviani Maria, Chellamuthu Vasuki Ranjani, Albani Salvatore, Low Andrea Hsiu Ling
Duke-National University of Singapore Medical School, Singapore 169857, Singapore.
Department of Rheumatology and Immunology, Singapore General Hospital, Singapore 169608, Singapore.
Int J Mol Sci. 2023 Sep 19;24(18):14287. doi: 10.3390/ijms241814287.
Systemic sclerosis (SSc) is an autoimmune disease associated with increased mortality and poor morbidity, impairing the quality of life in patients. Whilst we know that SSc affects multiple organs via vasculopathy, inflammation, and fibrosis, its exact pathophysiology remains elusive. Microvascular injury and vasculopathy are the initial pathological features of the disease. Clinically, the vasculopathy in SSc is manifested as Raynaud's phenomenon (reversible vasospasm in reaction to the cold or emotional stress) and digital ulcers due to ischemic injury. There are several reports that medications for vasculopathy, such as bosentan and soluble guanylate cyclase (sGC) modulators, improve not only vasculopathy but also dermal fibrosis, suggesting that vasculopathy is important in SSc. Although vasculopathy is an important initial step of the pathogenesis for SSc, it is still unclear how vasculopathy is related to inflammation and fibrosis. In this review, we focused on the clinical evidence for vasculopathy, the major cellular players for the pathogenesis, including pericytes, adipocytes, endothelial cells (ECs), and myofibroblasts, and their signaling pathway to elucidate the relationship among vasculopathy, inflammation, and fibrosis in SSc.
系统性硬化症（SSc）是一种自身免疫性疾病，与死亡率增加和发病率高相关，会损害患者的生活质量。虽然我们知道SSc通过血管病变、炎症和纤维化影响多个器官，但其确切的病理生理学仍不清楚。微血管损伤和血管病变是该疾病的初始病理特征。临床上，SSc中的血管病变表现为雷诺现象（对寒冷或情绪应激的可逆性血管痉挛）和因缺血性损伤导致的指端溃疡。有几份报告表明，用于治疗血管病变的药物，如波生坦和可溶性鸟苷酸环化酶（sGC）调节剂，不仅能改善血管病变，还能改善皮肤纤维化，这表明血管病变在SSc中很重要。虽然血管病变是SSc发病机制的一个重要初始步骤，但血管病变与炎症和纤维化之间的关系仍不清楚。在这篇综述中，我们重点关注了血管病变的临床证据、发病机制中的主要细胞成分，包括周细胞、脂肪细胞、内皮细胞（ECs）和成肌纤维细胞，以及它们的信号通路，以阐明SSc中血管病变、炎症和纤维化之间的关系。
