Molecular Pathogenesis of Connective Tissue Disease-Associated Pulmonary Arterial Hypertension: A Narrative Review

TL;DR

This review discusses the molecular causes and mechanisms of pulmonary arterial hypertension linked to connective tissue diseases, focusing on recent findings and potential biomarkers.

Contribution

The paper provides a comprehensive overview of recent advances in the molecular pathogenesis of CTD-PAH and highlights potential biomarkers and animal models.

Findings

CTD-PAH involves endothelial dysfunction, vascular remodeling, and immune dysregulation.

Autoantibodies, cytokines, and chemokines are potential serum biomarkers for CTD-PAH.

Animal models are crucial for understanding CTD-PAH pathogenesis and developing new therapies.

Abstract

Pulmonary arterial hypertension (PAH) is a lethal condition marked by the proliferation and remodeling of small pulmonary arteries, ultimately leading to right ventricular hypertrophy and right heart failure. PAH secondary to connective tissue diseases (CTDs) is a progressive complication with a complex pathogenesis that results in the reduced efficacy of vasodilation-based therapies and poor clinical outcomes. Systemic sclerosis is the most commonly associated CTD with PAH in Western countries and has been most extensively investigated. Systemic lupus erythematosus and other CTDs may also be associated with PAH; however, they are less studied. In this review, we explore the general pathobiology of PAH, with a particular emphasis on recent advances in the molecular pathogenesis of CTD-PAH, including endothelial cell dysfunction, dysregulated cell proliferation and vascular remodeling, extracellular matrix remodeling, in situ thrombosis, right ventricular dysfunction, genetic aberrations, and immune dysregulation. We also conduct a thorough investigation into the potential serum biomarkers and immune dysregulation associated with CTD-PAH, summarizing the associated autoantibodies, cytokines, and chemokines. Furthermore, relevant animal models that may help unravel the pathogenesis and contribute to the development of new treatments are also reviewed.

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