Dataset Information

Multiomic analysis of PI3K in Atrial Myopathy

ABSTRACT: Here, we undertook comprehensive physiological and molecular analyses in cardiac-specific transgenic mice with increased or decreased PI3K to assess the dose response impact of directly regulating PI3K. Elevated PI3K was associated with a dose-dependent increase in heart size, and preserved/enhanced function. In contrast, reduced PI3K led to cardiac dysfunction, fibrosis, arrhythmia, and increased susceptibility to atrial enlargement and thrombi. This phenotype was associated with dysregulation of a lipid species (GM3) that regulates the IGF1-PI3K pathway, cardiac stress and contractility genes. Proteomic profiling identified distinct signatures across atria with varying degrees of atrial dysfunction, enlargement, and presence of atrial thrombi.

INSTRUMENT(S): Q Exactive HF-X

ORGANISM(S): Mus Musculus (ncbitaxon:10090)

SUBMITTER: David Greening

PROVIDER: MSV000092855 | MassIVE |

SECONDARY ACCESSION(S): PXD045372

REPOSITORIES: MassIVE

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Publications

Distinct functional and molecular profiles between physiological and pathological atrial enlargement offer potential new therapeutic opportunities for atrial fibrillation.

Chen Yi Ching YC Wijekoon Seka S Matsumoto Aya A Luo Jieting J Kiriazis Helen H Masterman Emma E Yildiz Gunes G Cross Jonathon J Parslow Adam C AC Chooi Roger R Sadoshima Junichi J Greening David W DW Weeks Kate L KL McMullen Julie R JR

Clinical science (London, England : 1979) 20240801 15

Atrial fibrillation (AF) remains challenging to prevent and treat. A key feature of AF is atrial enlargement. However, not all atrial enlargement progresses to AF. Atrial enlargement in response to physiological stimuli such as exercise is typically benign and reversible. Understanding the differences in atrial function and molecular profile underpinning pathological and physiological atrial remodelling will be critical for identifying new strategies for AF. The discovery of molecular mechanisms ...[more]

PMID: 39018488

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