Cardiac adenylyl cyclase overexpression precipitates and aggravates age-related myocardial dysfunction.

ABSTRACT:

Aims

Increase of cardiac cAMP bioavailability and PKA activity through adenylyl-cyclase 8 (AC8) overexpression enhances contractile function in young transgenic mice (AC8TG). Ageing is associated with decline of cardiac contraction partly by the desensitization of β-adrenergic/cAMP signalling. Our objective was to evaluate cardiac cAMP signalling as age increases between 2 months and 12 months and to explore whether increasing the bioavailability of cAMP by overexpression of AC8 could prevent cardiac dysfunction related to age.

Methods and results

Cardiac cAMP pathway and contractile function were evaluated in AC8TG and their non-transgenic littermates (NTG) at 2- and 12 months old. AC8TG demonstrated increased AC8, PDE1, 3B and 4D expression at both ages, resulting in incre

SUBMITTER: Mougenot N 

PROVIDER: S-EPMC6755357 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature