Myocardial Hypertrophy and Compensatory Increase in Systolic Function in a Mouse Model of Oxidative Stress

Abstract

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.

S2 Heart Sound Detects Aortic Valve Calcification Independent of Hemodynamic Changes in Mice

“…The Adenine group had a significantly higher stroke volume index, LV ejection fraction, and LV mass when compared to the Control group. An increased or preserved ejection fraction has been associated with both systolic ( 34 ) and diastolic ( 35 ) dysfunction in non-CKD mouse models. An increase in stroke volume index and ejection fraction usually occurs due to volume overload, which commonly presents in dialysis patients and is an important prognostic factor in determining interventional outcome ( 36 ).…”

Impact of soft drink on skeletal formation indicated by RSPO2, HAO1, and RUNX2 gene expressions

“…It has been reported that the HAO1 have reported its highest expression value in G2 by 2.89-fold compared to the control group (p≥0.05, Figure2). The oxidative stress is known as the the changes between antioxident level and prooxidant [48]. The gradual significant increase of HAO1 resulted in the increasing of oxidative stress.…”