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Myosin isozyme synthesis and mRNA levels in pressure-overloaded rabbit hearts
Abstract:
The in vivo synthesis rates of myosin isozyme heavy chains beta and alpha were measured in right ventricular (RV) muscle at 2 and 4 days following pulmonary artery constriction in rabbits, together with measurements of their relative mRNA levels. The synthesis rate of beta-myosin heavy chains was elevated in 2-day (0.27 +/- 0.06 day-1 or 2.5 +/- 0.7 mg/g RV/day, mean +/- SD) and in 4-day (0.25 +/- 0.08 day-1 or 2.8 +/- 1.0 mg/g RV/day) pressure overload, when compared to untreated rabbits (0.15 +/- 0.04 day-1 or 1.5 +/- 0.4 mg/g RV/day). However, the synthesis rates of alpha-myosin heavy chains in the same hearts were not altered significantly. There was a differential increase in the fractional synthesis rate of beta vs. alpha heavy chains in 2-day and 4-day pressure overload and in 2-day shams, suggesting switching toward beta heavy chain synthesis had occurred at these time points. beta heavy chain synthesis, as a proportion of total (alpha + beta) heavy chain synthesis, was significantly higher in 4-day pressure overload (78 +/- 9%) than in 4-day sham rabbits (63 +/- 6%). This increase in relative beta-synthesis was associated with a significant increase in the relative proportion of beta heavy chain mRNA level (76 +/- 13% vs. 56 +/- 7%). Furthermore, relative beta-synthesis and the beta-mRNA levels correlated linearly with each other in all experimental groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Pulmonary artery constriction increases beta-myosin heavy chain synthesis and mRNA in rabbit right ventricles. This indicates a shift towards beta-myosin heavy chain production during pressure overload.
Area of Science:
- Cardiovascular Physiology
- Molecular Cardiology
- Cardiac Remodeling
Background:
- Right ventricular (RV) adaptation to pressure overload is crucial for maintaining cardiac function.
- Myosin heavy chains (MHCs) are key contractile proteins, with alpha and beta isoforms exhibiting different contractile properties.
- Understanding isoform switching in MHCs is vital for comprehending cardiac remodeling.
Purpose of the Study:
- To investigate the in vivo synthesis rates of beta- and alpha-myosin heavy chains (MHCs) in the rabbit right ventricle.
- To determine the relative mRNA levels of beta- and alpha-MHCs under pressure overload conditions.
- To assess the potential for MHC isoform switching in response to pulmonary artery constriction.
Main Methods:
- Measurement of in vivo synthesis rates of beta- and alpha-myosin heavy chains in rabbit right ventricular muscle.
- Quantification of relative mRNA levels for beta- and alpha-myosin heavy chains.
- Utilized pulmonary artery constriction model in rabbits to induce pressure overload.
Main Results:
- Beta-myosin heavy chain synthesis rate significantly increased in response to 2-day and 4-day pressure overload.
- Alpha-myosin heavy chain synthesis rates remained unchanged.
- A significant shift towards beta-myosin heavy chain synthesis and increased beta-myosin heavy chain mRNA proportion were observed, correlating linearly.
Conclusions:
- Pulmonary artery constriction induces a significant increase in beta-myosin heavy chain synthesis in the rabbit right ventricle.
- The observed changes suggest an adaptive isoform switch towards beta-myosin heavy chains under pressure overload.
- The regulation of this isoform switch is closely linked to the corresponding changes in beta-myosin heavy chain mRNA levels.