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Cardiomyocyte-specific PCSK9 deficiency compromises mitochondrial bioenergetics and heart function

ABSTRACT: Purpose: PCSK9, which regulates hepatic lipid homeostasis by modulating LDL levels, is expressed in small quantities in the heart, but its role is unknown. Here, we sought to determine its cardiac function and identify the mechanisms. Mice with heart-specific deletion of Pcsk9 had reduced contractile capacity, heart failure with preserved ejection fraction, and left ventricular dilatation at 28 weeks of age and died prematurely. Results: Transcriptomic analyses revealed alterations of signaling pathways linked to cardiomyopathy and energy metabolism. Mitochondrial membrane lipid composition and cristae morphology were also altered, impairing the assembly and activity of mitochondrial respiratory complexes. Mitochondrial oxidation was reduced and compensatory glycolytic energy production was insufficient to support demand. Conclusions: Thus, PCSK9 is a key factor in cardiac metabolic function and PCSK9 deficiency is linked to cardiomyopathy, impaired heart function, and compromised energy production.

ORGANISM(S): Mus musculus

PROVIDER: GSE178389 | GEO | 2023/07/12

REPOSITORIES: GEO

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Mouse heart proteomics in Oma1 and Cox10 deficient mice

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Nicotinamide Mononucleotide Requires SIRT3 to Improve Cardiac Function and Bioenergetics in a Friedreich’s Ataxia Cardiomyopathy Model

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2017-07-21 | PXD006754 | Pride

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PCSK9 is involved in human induced pluripotent stem cell proliferation through the regulation of the NODAL signaling pathway II

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