Antiendothelial Cells Antibodies in Patients with Systemic Sclerosis in Relation to Pulmonary Hypertension and Lung Fibrosis

Abstract Background The TβRII∆k-fib transgenic (TG) mouse model of scleroderma replicates key fibrotic and vasculopathic complications of systemic sclerosis through fibroblast-directed upregulation of TGFβ signalling. We have examined peroxisome proliferator-activated receptor (PPAR) pathway perturbation in this model and explored the impact of the pan-PPAR agonist lanifibranor on the cardiorespiratory phenotype. Methods PPAR pathway gene and protein expression differences from TG and WT sex-matched littermate mice were determined at baseline and following administration of one of two doses of lanifibranor (30 mg/kg or 100 mg/kg) or vehicle administered by daily oral gavage up to 4 weeks. The prevention of bleomycin-induced lung fibrosis and SU5416-induced pulmonary hypertension by lanifibranor was explored. Results Gene expression data were consistent with the downregulation of the PPAR pathway in the TβRII∆k-fib mouse model. TG mice treated with high-dose lanifibranor demonstrated significant protection from lung fibrosis after bleomycin and from right ventricular hypertrophy following induction of pulmonary hypertension by SU5416, despite no significant change in right ventricular systolic pressure. Conclusions In the TβRII∆k-fib mouse strain, treatment with 100 mg/kg lanifibranor reduces the development of lung fibrosis and right ventricular hypertrophy induced by bleomycin or SU5416, respectively. Reduced PPAR activity may contribute to the exaggerated fibroproliferative response to tissue injury in this transgenic model of scleroderma and its pulmonary complications.

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Infliximab Treatment in a Patient with Systemic Sclerosis Associated with Lung Fibrosis and Pulmonary Hypertension

Respiration ◽

10.1159/000090248 ◽

2008 ◽

Vol 75 (3) ◽

pp. 346-349 ◽

Cited By ~ 31

Author(s):

Elena Bargagli ◽

Mauro Galeazzi ◽

Francesca Bellisai ◽

Luca Volterrani ◽

Paola Rottoli

Keyword(s):

Pulmonary Hypertension ◽

Systemic Sclerosis ◽

Lung Fibrosis ◽

Infliximab Treatment

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Systemische Sklerose - eine systematische Übersicht

VASA ◽

10.1024/0301-1526/a000065 ◽

2011 ◽

Vol 40 (1) ◽

pp. 6-19 ◽

Cited By ~ 14

Author(s):

Klein-Weigel ◽

Opitz ◽

Riemekasten

Keyword(s):

Pulmonary Hypertension ◽

Systemic Sclerosis ◽

Task Force ◽

Systemische Sklerose ◽

Systematische Übersicht ◽

European Respiratory Society ◽

High Association ◽

Microscopic Features ◽

European Society Of Cardiology ◽

Genetic Burden

Due to its high association with Raynauds phenomenon systemic sclerosis (SSc) is probably the most common connective tissue disease seen by vascular specialists. In part 1 of our systematic overview we summarize classification concepts of scleroderma disorders, the epidemiologic and genetic burden, the complex pathophysiologic background, and the clinical features and the stage-dependent capillary microscopic features of SSc. Furthermore, we address the diagnostic recommendations propagated by the German Network for Systemic Sclerosis and the Task Force for Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology, the European Respiratory Society, and the International Society of Heart and Lung Transplantation.

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