Heart failure & cardiomyopathies
Skeletal Muscle SIRT3 Deficiency Contributes to Pulmonary Vascular Remodeling in Pulmonary Hypertension Due to Heart Failure With Preserved Ejection Fraction
Authors' conclusion
This study demonstrates a systemic pathogenic impact of skeletal muscle SIRT3 deficiency in remote pulmonary vascular remodeling and PH-HFpEF.
Study context
- Population
- Mouse and rat models of PH-HFpEF and humans with PH-HFpEF
- Comparison
- Skeletal muscle-specific Sirt3 knockout mice vs controls
Main finding
As reported in the abstract
- Sirt3skm-/- mice: reduced pulmonary vascular density, pulmonary vascular proliferative remodeling and elevated pulmonary pressures
- Elevated LOXL2 secretion by SIRT3-deficient skeletal muscle cells (mass spectrometry secretome)
- Elevated circulating and skeletal muscle LOXL2 in Sirt3skm-/- mice, a rat PH-HFpEF model and humans with PH-HFpEF
- CNPY2 increased in pulmonary artery endothelial and smooth muscle cells of Sirt3skm-/- mice and PH-HFpEF animal models; higher in pulmonary artery smooth muscle cells of obese vs nonobese subjects
- Recombinant LOXL2 promoted pulmonary artery endothelial cell migration/proliferation and smooth muscle cell proliferation via CNPY2-p53 signaling
- Skeletal muscle-specific Loxl2 deletion decreased CNPY2 expression and improved pulmonary pressures in high-fat diet-induced PH-HFpEF mice
Original publication
Skeletal Muscle SIRT3 Deficiency Contributes to Pulmonary Vascular Remodeling in Pulmonary Hypertension Due to Heart Failure With Preserved Ejection Fraction. Circulation. Published 28 May 2024. doi:10.
Summarised from the published abstract; every number is checked against it