A New Target for Pulmonary Vascular Remodelling Emerges from Ageing Pathways
A translational study published in Cardiovascular Research has identified a novel mechanism driving pulmonary arterial hypertension (PAH), a condition increasingly prevalent in the elderly. The research demonstrates that aged mice and those with a partial deficiency in the anti-ageing protein Klotho develop more severe PAH, characterised by elevated right ventricular pressure and vascular remodelling. This pathology is linked to significantly increased levels of fibroblast growth factor 23 (FGF23), a finding corroborated in serum from elderly PAH patients. Crucially, the study shows that FGF23 directly stimulates the hyperproliferation of pulmonary arterial smooth muscle cells (PASMCs) in vitro, and that neutralising FGF23 with an antibody in preclinical models reverses key disease metrics, including vascular remodelling and right heart dysfunction.
Why it might matter to you: While focused on pulmonary hypertension, this research into the Klotho/FGF23 signalling axis offers a compelling parallel for investigating fibrotic and remodelling processes in chronic liver diseases like cirrhosis and primary sclerosing cholangitis. The identification of FGF23 as a direct driver of pathological cell proliferation provides a mechanistic blueprint that could inform the search for similar soluble factors in hepatic stellate cell activation and liver fibrosis. For hepatology, this underscores the potential of targeting specific age-related metabolic and hormonal pathways to mitigate progressive tissue remodelling, a central challenge in managing advanced liver disease.
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