Gene expression in cardiac hypertrophy in rat and human heart muscle

Abstract

Changes in the cardiac contents of microsomal RNA and poly(A)-containing mRNA have been examined during induction and regression of heart muscle hypertrophy in rat hearts, as well as possible changes in the subcellular distribution and protein-synthetic activity of cardiac mRNA. In addition, cardiac biopsies from patients with mitral valve diseases were evaluated for their mRNA contents. Induction of heart muscle hypertrophy was accompanied by substantial increases in cardiac microsomal RNA (30-60%) and cardiac mRNA (20-80%). During regression of hypertrophy increased levels of cardiac microsomal RNA and mRNA returned to normal values within 10-16 days. In general, cardiac mRNA levels were lower in human heart muscle than in rat heart muscle. Since the subcellular distribution of the microsomal RNA and of the mRNA as well as the protein-synthetic activity of the mRNA were not changed in the hypertrophied animals as compared with normal animals, and since the cardiac contents of most specific cardiac mRNA species (mRNAs for MHC, MLC1 and MLC2, actin, tropomyosin, troponin-T, myoglobin) increased proportionately, it is concluded that during induction of hypertrophy activation of gene expression occurs and affects the genes coding for the major cardiac proteins to a similar extent. This does, however, not exclude the possibility of more specific shifts in isoprotein patterns and in the levels of their corresponding mRNAs. It is proposed that changes in cardiac mRNA levels are the major regulatory factor in causing changes in cardiac protein synthesis rates leading to the induction and regression of cardiac hypertrophy.

High-sensitivity troponin T is a prognostic marker for patients with aortic stenosis after valve replacement surgery

“…Stenosis of aortic valve increases pressure afterload and ventricular wall stress, resulting in pressure overload to the left ventricle. Indeed, the strong association between left ventricular mass and hs-TnT levels is also in line with experimental and clinical works showing the increased production of troponin T in human and rat myocardium during pressure overload [23]. The troponin elevation seen with left ventricular hypertrophy (LVH) may be the result of myocardial ischemia due to a supply/demand mismatch in hypertrophied myocytes [24].…”

Transgenic Mice with Cardiac-Specific Expression of Activating Transcription Factor 3, a Stress-Inducible Gene, Have Conduction Abnormalities and Contractile Dysfunction

“…Consistent with this notion, TG1 ventricles had significant down-regulation of myosin light chain 2 ventricular isoform (MLC2V) (63 Ϯ 19 versus 100 Ϯ 17, P ϭ 0.0116), a down-regulation also observed in tissues from hypertrophic human hearts and in hypertrophic and hypertensive primate and rodent models. [25][26][27][28] SERCA2a, a marker of heart failure 29 -31 was not significantly different in the ventricles or atria of either line. It is apparent from the literature that different patterns of dysregulation for hypertrophic markers characterize specific murine models; importantly, although some markers may not be up-regulated in specific models, an increase in ␣-skeletal actin is always observed.…”

Troponin T Expression in Normal and Pressure-Loaded Fetal Sheep Heart

“…in samples taken from human hearts at autopsy or surgery (2)(3)(4) In our present study, we elected to use the fetal lamb as a have been noted. For example, Aukland et al (2) found that the model for congenital pulmonary stenosis and preductal coarctapattern of myosin iight chain isotype expression was altered in tion of the AO by banding the great vessels in vlero.…”

“…3. Derived amino acid sequence of the dominant isoform of sheep cardiac TNT compared with other mammalian cardiac TNT amino acid sequences.…”