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Regional myosin heavy chain expression in volume and pressure overload induced cardiac hypertrophy
1Department of Pharmacology and Toxicology, Queen's University, Kingston, Ontario, Canada.
Insights
Regional V3 myosin heavy chain (MHC) expression differs between pressure and volume overload cardiac hypertrophy. This study reveals distinct regional V3 MHC expression patterns in the left ventricle, highlighting adaptive responses to hemodynamic stress.
Area of Science:
- Cardiovascular Physiology
- Molecular Cardiology
- Cardiac Hypertrophy Research
Background:
- The shift to V3 myosin heavy chain (MHC) is linked to cardiac hypertrophy, but regional expression data is limited.
- Understanding regional differences in myosin isoform expression is crucial for comprehending adaptive mechanisms in heart disease.
Purpose of the Study:
- To quantitatively compare and contrast regional ventricular myosin isoform expression in pressure and volume overload models.
- To investigate the relationship between V3 MHC expression and cardiac hypertrophy in distinct hemodynamic states.
Main Methods:
- Utilized aortocaval fistula (ACF) for volume overload and two-kidney-one-clip (2K1C) for pressure overload in rat models.
- Analyzed myosin expression in right ventricle, septum, and left ventricular free wall samples using polyacrylamide gel electrophoresis.
- Differentiated endocardial and epicardial expression patterns in the left ventricle and septum.
Main Results:
- Both ACF and 2K1C models induced significant cardiac hypertrophy, with distinct blood pressure responses.
- V3 MHC expression correlated with left ventricular hypertrophy in both models.
- A significant endo-epi differential in V3 MHC expression was observed in the 2K1C model, but not in the ACF model.
Conclusions:
- Regional V3 myosin expression is a distinct adaptive component of cardiac hypertrophy in response to both volume and pressure overload.
- The observed regional differences in V3 MHC expression correlate with known transmural myocyte hypertrophy patterns.
- Elevated V3 MHC expression persisted even after regression of hypertrophy and normalization of blood pressure.
Abstract:
Although the overall shift towards the V3 myosin heavy chain (MHC) has been shown to be associated with cardiac hypertrophy, quantitative evidence describing regional expression is sparse. The aim of this study was to compare and contrast the regional ventricular myosin isoform expression in two distinct haemodynamic states: pressure and volume overload. Volume overload was achieved using an aortocaval fistula (ACF) model and pressure overload by two-kidney-one-clip (2K1C) hypertension. A separate group (UC-2K1C) had the clip removed 1 week prior to investigation. Sham operated rats (SHAM) served as controls. All groups were studied 4 weeks after surgery. Ventricular tissue samples (approximately 50 mg) were taken from the walls of the right ventricle (RV), septum and left ventricular (LV) free wall. Tissue samples (excluding RV) were divided into endocardium and epicardium, and myosin expression was determined using polyacrylamide gel electrophoresis. Cardiac hypertrophy was substantial in both LV (1.7-fold) and RV (1.9-fold) in ACF rats. The 2K1C rats had similar LV enlargement (1.6-fold) whereas RV hypertrophy was not as great (1.2-fold). Blood pressure (BP) was increased 65% in 2K1C rats, whereas there was no change in ACF rats with respect to SHAM animals. After unclipping (UC-2K1C), LV hypertrophy and BP had returned towards control levels. In general, V3 MHC expression was associated with increasing LV hypertrophy in both 2K1C and ACF models. However, there was a marked endo-epi differential (1.5:1) in the LV free wall and septum of 2K1C rats. In contrast, in ACF rats there was no differential V3 MHC expression in the LV or septal tissue, i.e. expression was similar in both endo- and epi-samples. Elevated expression of V3 MHC persisted despite normotension and regression of cardiac hypertrophy in UC-2K1C rats. Taken together with published results demonstrating that relative transmural myocyte hypertrophy in ACF rats (endo > epi) is in contrast to that seen in 2K1C rats (epi > endo), the present findings reveal that regional V3 myosin expression represents a distinct adaptational component of the overall cardiac hypertrophic response in both volume and pressure overload.