Dysregulated Klotho and FGF23 signaling aggravates vascular remodeling in age-related pulmonary hypertension - PubMed
6 hours ago
- #pulmonary hypertension
- #vascular remodeling
- #aging
- Pulmonary arterial hypertension (PAH) is a chronic condition caused by vascular remodeling due to increased proliferation of pulmonary arterial smooth muscle cells (PASMC).
- Initially affecting young women, PAH now increasingly affects the elderly, but age-related mechanisms remain unclear.
- The study explores the role of the anti-aging protein Klotho and fibroblast growth factor 23 (FGF23) in PAH pathogenesis.
- Aged mice and Klotho-deficient mice showed moderate PAH, right ventricular hypertrophy, and dysfunction, worsened by hypoxia.
- Elevated plasma FGF23 levels were found in aged mice, Klotho-deficient mice, and elderly PAH patients.
- FGF23 increased PASMC proliferation, which was prevented by fibroblast growth factor receptor 1 knockdown.
- Neutralizing FGF23 in Klotho-deficient mice reduced PAH symptoms and vascular remodeling.
- The study identifies FGF23 accumulation as a novel mechanism in PAH vascular remodeling.
- Targeting dysregulated Klotho/FGF23 signaling may offer a therapeutic strategy for elderly PAH patients.