Isomyosins, microtubules and desmin during the onset of cardiac hypertrophy in the rat

Abstract

Chronic overloading of the rat heart induces a cascade of adaptational events which compensate for the increase in work. Two of these have been extensively described: a qualitative event with an isomyosin change leading to an improved efficiency and a quantitative event resulting in cardiac hypertrophy. By means of immunofluorescence, we investigated if elements of the cytoskeleton, i.e. microtubules and intermediate filaments, could be triggers for these adaptational mechanisms. Studies of overloaded heart were performed in young rats with aortic stenosis or adult rats with aortic insufficiency. Cardiac myocytes were isolated and labelled by immunofluorescence with antibodies raised against V1 or V3 isomyosin, desmin or tubulin. The aim of the work was to visualize: when and where the shift in the expression of isomyosins occurs within the myocytes; the eventual changes in the pattern of intermediate filaments of desmin and/or of microtubules during the adaptation of myocytes to overload. We observed: that the shift from the high (V1) to low (V3) ATPase isomyosin occurred in a population of myocytes soon after stenosis; that changes in the pattern of microtubules occurred soon after induction of hypertrophy; no changes in the distribution or intensity of the staining of desmin.

Nonsynchronous accumulation of alpha-skeletal actin and beta-myosin heavy chain mRNAs during early stages of pressure-overload--induced cardiac hypertrophy demonstrated by in situ hybridization.

“…Thus, even minor increases in /3-MHC and a-sk-actin mRNAs can be expected to be easily identified, as was previously shown at the protein level for /3-MHC using immunocytochemical methods. 11 Through use of /3-MHC and a-sk-actin genespecific probes and in situ hybridization procedures, we show here that the accumulation of the corresponding mRNAs in the ventricular wall is neither spatially nor temporally coordinated after aortic banding.…”

Microtubules Modulate the Stiffness of Cardiomyocytes Against Shear Stress

“…Because microtubules have been implicated in many pathological conditions of the heart, such as cardiac hypertrophy, heart failure, and ischemia, 5,6,28 many researchers have studied their roles in determining the mechanical properties. [11][12][13]29,30 These studies by applying either stretch or anisoosmotic stress to the myocyte or muscle preparations found no significant change in the passive stiffness of the myocardium 11,12,29,30 but only found an effect on viscosity of the microtubule proliferation.…”

“…Their relative content of microtubules (tubulin) is small compared with other types of cells 4 but increases in various disease conditions, such as cardiac hypertrophy or heart failure, in which the heart is subjected to abnormally high loads. 5,6 In this context, studies at the tissue (papillary muscle) and cellular levels have focused on the impact of microtubule proliferation on the contractile function of the myocardium, but the results obtained are controversial. The microtubule proliferation observed in hypertrophied hearts was associated with contractile dysfunction and pharmacological disruption of the microtubules by colchicines (COLs) normalized the contractile function.…”

β-Myosin Heavy Chain Is Induced by Pressure Overload in a Minor Subpopulation of Smaller Mouse Cardiac Myocytes

“…First, β-MyHC should be induced in most or all myocytes in a hypertrophied heart, and, second, the myocytes expressing β-MyHC should be hypertrophied, or larger in size. However, a few reports indicate that endogenous β-MyHC is expressed heterogeneously in the overloaded myocardium, 15,16 a mean 30% of myocytes in one report, 15 and the same can be true for other fetal genes. 16–18 The most extensive study used a knockin reporter mouse with yellow fluorescent protein (YFP) fused to the N-terminus of β-MyHC (YFP-β-MyHC).…”