A novel human S10F-Hsp20 mutation induces lethal peripartum cardiomyopathy.
Guan-Sheng LiuGeorge GardnerGeorge AdlyMin JiangWen-Feng CaiChi Keung LamFawzi AlogailiNathan RobbinsJack RubinsteinEvangelia G KraniasPublished in: Journal of cellular and molecular medicine (2018)
Heat shock protein 20 (Hsp20) has been shown to be a critical regulator of cardiomyocyte survival upon cardiac stress. In this study, we investigated the functional significance of a novel human Hsp20 mutation (S10F) in peripartum cardiomyopathy. Previous findings showed that cardiac-specific overexpression of this mutant were associated with reduced autophagy, left ventricular dysfunction and early death in male mice. However, this study indicates that females have normal function with no alterations in autophagy but died within a week after 1-4 pregnancies. Further examination of mutant females revealed left ventricular chamber dilation and hypertrophic remodelling. Echocardiography demonstrated increases in left ventricular end-systolic volume and left ventricular end-diastolic volume, while ejection fraction and fractional shortening were depressed following pregnancy. Subsequent studies revealed that cardiomyocyte apoptosis was elevated in mutant female hearts after the third delivery, associated with decreases in the levels of Bcl-2/Bax and Akt phosphorylation. These results indicate that the human S10F mutant is associated with dysregulation of cell survival signalling, accelerated heart failure and early death post-partum.
Keyphrases
- left ventricular
- heart failure
- heat shock protein
- aortic stenosis
- cardiac resynchronization therapy
- hypertrophic cardiomyopathy
- endothelial cells
- ejection fraction
- acute myocardial infarction
- left atrial
- mitral valve
- heat shock
- endoplasmic reticulum stress
- cell death
- signaling pathway
- oxidative stress
- heat stress
- pluripotent stem cells
- randomized controlled trial
- wild type
- clinical trial
- blood pressure
- single cell
- preterm birth
- mass spectrometry
- atrial fibrillation
- transcatheter aortic valve replacement
- induced apoptosis
- coronary artery disease
- high resolution
- atomic force microscopy
- angiotensin ii
- stress induced
- pulmonary hypertension
- high speed
- pi k akt
- percutaneous coronary intervention