Why fibrosis after exposure to low frequency noise? (original) (raw)

Unique patterns of cardiogenic and fibrotic gene expression in rat cardiac fibroblasts

Veterinary World, 2020

Background and Aim: Cardiac fibroblasts are important for both normal and pathological states of the heart, but the knowledge in cell physiology and genomics is still poorly understood. The aims of the present study were; first, to investigate the expression of cardiac and fibrotic genes in rat cardiac fibroblasts compared to cardiomyocytes and other fibroblasts (skin and muscle fibroblasts), second, to examine the in vitro effect of serum concentration on fibroblast gene expression. The findings can potentially be applied in ischemia/reperfusion models. Materials and Methods: Rat cardiac fibroblasts were collected and cultured in different conditions, and their gene expression (21 cardiogenic genes and 16 fibrotic genes) was compared with cardiomyocytes and other fibroblasts using comparative quantitative polymerase chain reaction. We also mimicked myocardial ischemia/reperfusion by depleting and then adding a serum into the culture in conventional culture (10% serum). Results: Cardiac fibroblasts expressed most of the cardiogenic genes, but their expression levels were significantly lower than in cardiomyocytes, while almost all fibrotic genes in the cardiac fibroblasts were significantly more highly expressed than in cardiomyocytes, except matrix metallopeptidase 9 (Mmp9) which also had greater expression in other fibroblasts. After mimicking cardiac ischemia and reperfusion in vitro by starving and then adding a serum into the cardiac fibroblast culture, the results revealed that Mmp9 expression was significantly increased (>30 times) after increasing but not reducing the serum in the culture. The expression of most cardiogenic and fibrotic genes in cardiac fibroblasts tended to decrease after increasing the serum in the culture. These changes were specific to cardiac fibroblasts but no other fibroblasts. Conclusion: Cardiac fibroblasts have a distinct pattern of gene expression from other fibroblasts and cardiomyocytes. They are also sensitive to high serum concentration but not affected by serum depletion, suggesting that the process of developing cardiac fibrosis might be stimulated by reperfusion or overcirculation rather than ischemia. The cell starvation followed the adding of serum may serve as a useful model to study cardiac fibrosis cause by the change of blood flow.

Myocardial fibrosis in rats exposed to low frequency noise

Acta cardiologica, 2013

Low frequency noise (LFN) characterized by large pressure amplitude (> or =90 dB SPL) and low frequency bands (< or =500 Hz) can lead to structural and ultrastructural modifications in the extracellular matrix of several tissues, with an abnormal proliferation of collagen and development of fibrosis. It is not known whether LFN induces similar structural alterations in the ventricular myocardium of rats. The aim of this study was to evaluate and measure the myocardial fibrosis induced by LFN. Two groups of…

Changing Patterns of Gene Expression in the Pulmonary Trunk-banded Rat Heart

Journal of Molecular and Cellular Cardiology, 1998

A pressure-overload model in the rat by banding the pulmonary trunk (PT) was developed to investigate alterations in gene expression in left-and right-ventricular compartments during the transition from compensated right-ventricular (RV) hypertrophy to right heart failure. Right heart failure in rat is characterized by liver cirrhosis, hydrothorax and ascites. The diameter of constriction was found to determine the time course of heart failure development. Only the RV free wall and the right atrium increased in weight, without a difference between compensated and failing RV. An increase in circulating ANP revealed a hypertrophic response of the myocardium, while increased circulating ammonia levels discriminated between compensated hypertrophy and failure. As parameters for stress, fibrosis and Ca 2+ -handling, changes in the pattern and level of the mRNAs encoding atrial natriuretic peptide (ANP), collagenIII 1 , and sarcoplasmic endoplasmic reticular calcium ATPase 2 (SERCA2), phospholamban (PLB) and calsequestrin (CSQ) were studied by Northern blot and in situ hybridization analyses. Pulmonary trunk banding resulted in an induction of ANP mRNA, a moderate increase in collagenIII 1 mRNA and a decrease in SERCA2 and PLB mRNA levels in both the left and right ventricles, but changes were most pronounced in the myocardium surrounding the RV cavity. Increased ammonia blood levels are a promising prognostic marker to detect the development of right heart failure.

Cellular repressor of E1A-stimulated genes attenuates cardiac hypertrophy and fibrosis

Journal of Cellular and Molecular Medicine, 2009

Cellular repressor of E1A-stimulated genes (CREG) is a secreted glycoprotein of 220 amino acids. It has been proposed that CREG acts as a ligand that enhances differentiation and/or reduces cell proliferation. CREG has been shown previously to attenuate cardiac hypertrophy in vitro. However, such a role has not been determined in vivo. In the present study, we tested the hypothesis that overexpression of CREG in the murine heart would protect against cardiac hypertrophy and fibrosis in vivo. The effects of constitutive human CREG expression on cardiac hypertrophy were investigated using both in vitro and in vivo models. Cardiac hypertrophy was produced by aortic banding and infusion of angiotensin II in CREG transgenic mice and control animals. The extent of cardiac hypertrophy was quantitated by two-dimensional and M-mode echocardiography as well as by molecular and pathological analyses of heart samples. Constitutive over-expression of human CREG in the murine heart attenuated the hypertrophic response, markedly reduced inflammation. Cardiac function was also preserved in hearts with increased CREG levels in response to hypertrophic stimuli. These beneficial effects were associated with attenuation of the mitogen-activated protein kinase (MAPK)-extracellular signal-regulated kinase 1 (MEK-ERK1)/2-dependent signalling cascade. In addition, CREG expression blocked fibrosis and collagen synthesis through blocking MEK-ERK1/2-dependent Smad 2/3 activation in vitro and in vivo. Therefore, the expression of CREG improves cardiac functions and inhibits cardiac hypertrophy, inflammation and fibrosis through blocking MEK-ERK1/2-dependent signalling.

Stress-induced differential gene expression in cardiac tissue

Scientific Reports, 2021

The stress response is adaptive and aims to guarantee survival. However, the persistence of a stressor can culminate in pathology. Catecholamines released as part of the stress response over activate beta adrenoceptors (β-AR) in the heart. Whether and how stress affects the expression of components of the intracellular environment in the heart is still, however, unknown. This paper used microarray to analyze the gene expression in the left ventricle wall of rats submitted to foot shock stress, treated or not treated with the selective β2-AR antagonist ICI118,551 (ICI), compared to those of non-stressed rats also treated or not with ICI, respectively. The main findings were that stress induces changes in gene expression in the heart and that β2-AR plays a role in this process. The vast majority of genes disregulated by stress were exclusive for only one of the comparisons, indicating that, in the same stressful situation, the profile of gene expression in the heart is substantially d...

Altered Expression of ORAI and STIM Isoforms in Activated Human Cardiac Fibroblasts

Physiological Research, 2021

Cardiac fibrotization is a well-known process characteristic of many cardiac pathological conditions. The key element is excessive activation of cardiac fibroblasts, their transdifferentiation into myofibroblasts, increased production, and accumulation of extracellular matrix proteins, resulting in cardiac stiffness. The exact cellular mechanisms and molecular components involved in the process are not fully elucidated, but the SOCE mechanism could play an important role. Its key molecules are the molecular sensor of calcium in ER/SR-STIM and the highly selective calcium channels Orai located in the plasma membrane. This study aims to evaluate selected SOCEassociated genes in the activation of HCF cell culture by several known substances (phenylephrine, isoprenaline) that represent cardiovascular overload. After cell cultivation, cell medium was collected to measure the soluble collagen content. From the harvested cells, qRT-PCR was performed to determine the mRNA levels of the corresponding genes. The activation of cells was based on changes in the relative expression of collagen genes as well as the collagen content in the medium of the cell culture. We detected an increase in the expression of the Orai2 isoform, a change in the Orai1/Orai3 ratio and also an increase in the expression of the STIM2 isoform. These results suggest an increased activation of the SOCE mechanism under stress conditions of fibroblasts, which supports the hypothesis of fibroblast activation in pathological processes by altering calcium homeostasis through the SOCE mechanism.