Myocardial Hypertrophy and Compensatory Increase in Systolic Function in a Mouse Model of Oxidative Stress.
Rohan VarshneyRojina RanjitYing Ann ChiaoMichael KinterBumsoo AhnPublished in: International journal of molecular sciences (2021)
Free radicals, or reactive oxygen species, have been implicated as one of the primary causes of myocardial pathologies elicited by chronic diseases and age. The imbalance between pro-oxidants and antioxidants, termed "oxidative stress", involves several pathological changes in mouse hearts, including hypertrophy and cardiac dysfunction. However, the molecular mechanisms and adaptations of the hearts in mice lacking cytoplasmic superoxide dismutase (Sod1KO) have not been investigated. We used echocardiography to characterize cardiac function and morphology in vivo. Protein expression and enzyme activity of Sod1KO were confirmed by targeted mass spectrometry and activity gel. The heart weights of the Sod1KO mice were significantly increased compared with their wildtype peers. The increase in heart weights was accompanied by concentric hypertrophy, posterior wall thickness of the left ventricles (LV), and reduced LV volume. Activated downstream pathways in Sod1KO hearts included serine-threonine kinase and ribosomal protein synthesis. Notably, the reduction in LV volume was compensated by enhanced systolic function, measured by increased ejection fraction and fractional shortening. A regulatory sarcomeric protein, troponin I, was hyper-phosphorylated in Sod1KO, while the vinculin protein was upregulated. In summary, mice lacking cytoplasmic superoxide dismutase were associated with an increase in heart weights and concentric hypertrophy, exhibiting a pathological adaptation of the hearts to oxidative stress.
Keyphrases
- oxidative stress
- left ventricular
- amyotrophic lateral sclerosis
- heart failure
- ejection fraction
- aortic stenosis
- hypertrophic cardiomyopathy
- high fat diet induced
- mouse model
- dna damage
- blood pressure
- mass spectrometry
- reactive oxygen species
- ischemia reperfusion injury
- induced apoptosis
- protein kinase
- atrial fibrillation
- hydrogen peroxide
- computed tomography
- type diabetes
- high resolution
- amino acid
- liquid chromatography
- pulmonary hypertension
- protein protein
- transcription factor
- wild type
- high intensity
- binding protein
- insulin resistance
- drug delivery
- cancer therapy
- adipose tissue
- anti inflammatory
- nitric oxide
- aortic valve