Review
Rheumatology
Yasushi Kawaguchi, Masataka Kuwana
Summary: In patients with systemic sclerosis (SSc), vascular manifestations precede skin and organ fibrosis. There is increasing evidence demonstrating a pathogenic link between early vascular injury and subsequent development of tissue fibrosis.
CURRENT OPINION IN RHEUMATOLOGY
(2023)
Article
Hematology
Yali Yu, Yu Leng, Xiuyue Song, Jie Mu, Lei Ma, Lin Yin, Yu Zheng, Yi Lu, Yuanming Li, Xuefeng Qiu, Hai Zhu, Jing Li, Dong Wang
Summary: This study investigated how ECM stiffness regulates microvascular endothelial cells and pericytes, as well as the mechanisms of pericyte-myofibroblast differentiation. The results showed that soft ECM and TGF-β signaling inhibitor A83-01 cooperatively maintained microvascular stability and inhibited pericyte-myofibroblast differentiation. Soft ECM also promoted microvascular regeneration and inhibited fibrosis in bone graft transplantation.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2023)
Review
Rheumatology
Jakob Hoeppner, Cosimo Bruni, Oliver Distler, Simon C. Robson, Gerd R. Burmester, Elise Siegert, Jorg H. W. Distler
Summary: SSc is a chronic autoimmune rheumatic disease with histopathological hallmarks including vasculopathy, fibrosis, and autoimmune phenomena. Purinergic signalling pathway may play a role in the pathophysiology of SSc, exacerbating vasculopathy and immune dysregulation, while also promoting organ and tissue fibrosis. Targeting purinergic signalling could offer new therapeutic options for SSc.
Review
Biochemistry & Molecular Biology
Weiming Zhao, Lan Wang, Yaxuan Wang, Hongmei Yuan, Mengxia Zhao, Hui Lian, Shuaichen Ma, Kai Xu, Zhongzheng Li, Guoying Yu
Summary: The pathological features of pulmonary fibrosis (PF) involve abnormal activation and proliferation of myofibroblasts as well as excessive deposition of extracellular matrix (ECM). Recent studies have emphasized the crucial role of endothelial cells in the development of PF, with 16% of fibroblasts in fibrotic mice lung tissue being derived from endothelial cells. The endothelial cells undergo endothelial-mesenchymal transition (E(nd)MT), leading to excessive proliferation of endothelial-derived mesenchymal cells, fibroblast accumulation, and ECM deposition.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Irene Rosa, Eloisa Romano, Bianca Saveria Fioretto, Khadija El Aoufy, Silvia Bellando-Randone, Marco Matucci-Cerinic, Mirko Manetti
Summary: Currently, only a few studies have investigated the role of the lymphatic vascular system in the pathogenesis of systemic sclerosis (SSc). This study aimed to explore the possibility of lymphatic endothelial cells undergoing an endothelial-to-myofibroblast transition (Ly-EndMT) and contributing to skin fibrosis in SSc. The results demonstrated the presence of lymphatic endothelial cells in intermediate stages of the Ly-EndMT process exclusively in the fibrotic skin of SSc patients, suggesting that Ly-EndMT might be a previously overlooked pathogenic process linking peripheral microlymphatic dysfunction and skin fibrosis development in SSc.
Article
Physiology
Rebecca L. Ross, Georgia Mavria, Francesco Del Galdo, Jacobo Elies
Summary: This study investigates the role of hemeoxygenase-1 (HO-1) and its relevance in cardiovascular complications occurring in systemic sclerosis (SSc). The study shows that the expression of HO-1 is lower in dermal fibroblast of SSc patients and this reduction is associated with endothelial dysfunction and vasculopathy. The study also demonstrates the role of HO-1/carbon monoxide (CO) signaling pathway in calcium handling, angiogenesis, and cardiac action potential modulation.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Cardiac & Cardiovascular Systems
Shaohua Zhang, Yan Li, Xiuzhen Huang, Kuo Liu, Qing-Dong Wang, Alex F. Chen, Kun Sun, Kathy O. Lui, Bin Zhou
Summary: The study reveals that during cardiac development, cardiac ECs can transdifferentiate into mesenchymal cells through EndoMT but do not contribute to myofibroblasts or express known mesenchymal genes transiently during fibrosis in the adult heart. Resident fibroblasts are the major contributors to cardiac fibrosis by activating mesenchymal gene expression.
Article
Medicine, General & Internal
Cosimo Bruni, Laura Cometi, Antonietta Gigante, Edoardo Rosato, Marco Matucci-Cerinic
Summary: The study found that arthritis and dyspnea are independent predictors of major vascular complications in patients with Systemic Sclerosis. While vasoactive/vasodilating drugs did not have a primary preventive effect on MVCs development, certain medications were able to slow disease progression and delay the onset of major vascular complications.
EUROPEAN JOURNAL OF INTERNAL MEDICINE
(2021)
Review
Biochemistry & Molecular Biology
Bianca Saveria Fioretto, Irene Rosa, Marco Matucci-Cerinic, Eloisa Romano, Mirko Manetti
Summary: Systemic sclerosis (SSc, scleroderma) is a rare connective tissue disease characterized by immune dysregulation, small vessel vasculopathy, impaired angiogenesis, and fibrosis. Microvascular impairment is the initial event of the disease and is linked to disabling and life-threatening clinical manifestations. Despite available treatment options, managing SSc-related vascular disease remains challenging. Vascular biomarkers have shown promise in assessing disease progression, predicting prognosis, and guiding therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Bai Ruan, Juan-Li Duan, Hao Xu, Kai-Shan Tao, Hua Han, Guo-Rui Dou, Lin Wang
Summary: Liver sinusoidal endothelial cells undergo partial endothelial mesenchymal transition during liver fibrosis, leading to increased extracellular matrix production without activating cell mobility. Targeting this transitional process may be valuable for antifibrotic treatment of liver fibrosis.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Immunology
Benjamin Chaigne, Sarah Leonard-Louis, Luc Mouthon
Summary: Scleroderma associated myopathy (SScAM) is a heterogeneous musculoskeletal manifestation of systemic sclerosis (SSc) that lacks a clear definition. However, SScAM is associated with disability, poor quality of life, and mortality. This review provides an overview of the most up-to-date literature on SScAM, including clinical and antibody associations, recent histopathological findings, prognosis, and treatment.
AUTOIMMUNITY REVIEWS
(2023)
Review
Pharmacology & Pharmacy
Hong-Yan Zhou, Hua Sui, Yang-Jianing Zhao, Hong-Jie Qian, Nan Yang, Lu Liu, Qing Guan, Yue Zhou, Hong-Li Lin, Da-Peng Wang
Summary: Inflammation and tissue damage lead to fibrosis, and the vascular niche plays a key role in regulating inflammation and influencing organ damage repair. The vascular niche can regulate macrophages, endothelial cell transformation, and provide new ideas for anti-fibrosis drug research.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Immunology
Lamia Khan, Tahlia Derksen, Desiree Redmond, Jan Storek, Caylib Durand, Robert Gniadecki, Benjamin Korman, Jan Willem Cohen Tervaert, Ana D'Aubeterre, Mohammed S. Osman, Lisa M. Willis
Summary: This study found that polySia is dysregulated in patients with systemic sclerosis (SSc) and correlates with the degree of skin fibrosis. The aberrant expression of polySia highlights its potential use as a biomarker in patients with progressive forms of SSc. Dysregulated polySia levels in SSc further emphasizes the cancer-like phenotype present in SSc, which may promote fibrosis and immune dysregulation.
JOURNAL OF AUTOIMMUNITY
(2023)
Article
Physiology
Chi F. Hung, Carole L. Wilson, Yu-Hua Chow, Wayne C. Liles, Sina A. Gharib, William A. Altemeier, Lynn M. Schnapp
Summary: This study investigates the role of pericyte-like cells in lung fibrosis by using a model of pericyte-like cell ablation. The results show that pericyte-like cell ablation does not affect lung fibrosis but reduces acute lung inflammation.
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
(2022)
Review
Rheumatology
Tracy M. Frech
Summary: This review discusses the imaging techniques for vascular assessment in systemic sclerosis (SSc), including nailfold and oral capillaroscopy, laser speckle contrast analysis, ultrasound techniques, and mobile infrared thermography and optical coherence tomography. The equipment cost, technical training, data standardization, and invasiveness of these techniques are critical for their implementation in SSc clinical trials and practice to understand progressive vasculopathy.
CURRENT OPINION IN RHEUMATOLOGY
(2022)
Article
Rheumatology
Eloisa Romano, Irene Rosa, Bianca Saveria Fioretto, Dilia Giuggioli, Mirko Manetti, Marco Matucci-Cerinic
Summary: Pharmacological sGC stimulation effectively improves the angiogenic performance and reduces the myofibroblast-like profibrotic phenotype of SSc-MVECs, providing new evidence for repurposing sGC stimulators for the treatment of SSc.
Review
Biochemistry & Molecular Biology
Bianca Saveria Fioretto, Irene Rosa, Marco Matucci-Cerinic, Eloisa Romano, Mirko Manetti
Summary: Systemic sclerosis (SSc, scleroderma) is a rare connective tissue disease characterized by immune dysregulation, small vessel vasculopathy, impaired angiogenesis, and fibrosis. Microvascular impairment is the initial event of the disease and is linked to disabling and life-threatening clinical manifestations. Despite available treatment options, managing SSc-related vascular disease remains challenging. Vascular biomarkers have shown promise in assessing disease progression, predicting prognosis, and guiding therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Rheumatology
Edda Russo, Silvia Bellando-Randone, Davide Carboni, Bianca Saveria Fioretto, Eloisa Romano, Simone Baldi, Khadija El Aoufy, Matteo Ramazzotti, Irene Rosa, Gemma Lepri, Leandro Di Gloria, Marco Pallecchi, Cosimo Bruni, Daniela Melchiorre, Serena Guiducci, Mirko Manetti, Gian Luca Bartolucci, Marco Matucci-Cerinic, Amedeo Amedei
Summary: This study characterized the microbiota in SSc patients and found different microbiota profiles and FFA profiles between ACA+ and anti-Scl70+ groups. The cutaneous Sphingobacteria and faecal Lentisphaerae were interdependent in ACA+ patients. The findings suggest a potential role of the microbiota and FFAs in the pathogenesis of SSc.
Article
Cell Biology
Elena Andreucci, Bianca Saveria Fioretto, Irene Rosa, Marco Matucci-Cerinic, Alessio Biagioni, Eloisa Romano, Lido Calorini, Mirko Manetti
Summary: This study reveals a previously unrecognized relationship between lactic acidosis and the generation of a new CAF-like cell subpopulation from adipocytic precursor cells, which sustains tumor malignancy.
Editorial Material
Biology
Eloisa Romano, Irene Rosa, Mirko Manetti
Article
Cell Biology
Irene Rosa, Patrizia Nardini, Bianca Saveria Fioretto, Daniele Guasti, Eloisa Romano, Eleonora Sgambati, Mirca Marini, Mirko Manetti
Summary: Telocytes (TCs) have been found to exist in the stromal tissue of the human vaginal mucosa and are characterized by their presence in the perivascular networks and release of extracellular vesicles. Further investigation is needed to determine the functions of TCs in vaginal mucosal homeostasis and pathophysiology.
Article
Cell Biology
Irene Rosa, Eloisa Romano, Bianca Saveria Fioretto, Khadija El Aoufy, Silvia Bellando-Randone, Marco Matucci-Cerinic, Mirko Manetti
Summary: Currently, only a few studies have investigated the role of the lymphatic vascular system in the pathogenesis of systemic sclerosis (SSc). This study aimed to explore the possibility of lymphatic endothelial cells undergoing an endothelial-to-myofibroblast transition (Ly-EndMT) and contributing to skin fibrosis in SSc. The results demonstrated the presence of lymphatic endothelial cells in intermediate stages of the Ly-EndMT process exclusively in the fibrotic skin of SSc patients, suggesting that Ly-EndMT might be a previously overlooked pathogenic process linking peripheral microlymphatic dysfunction and skin fibrosis development in SSc.
Letter
Rheumatology
Mirko Manetti
ANNALS OF THE RHEUMATIC DISEASES
(2023)