Structural analysis of pressure versus volume overload hypertrophy of cat right ventricle

Marino, Thomas A.; Kent, Robert L.; Uboh, Cornelius E.; Fernández, E. Becerra; Thompson, E. W.; Cooper, George

doi:10.1152/ajpheart.1985.249.2.h371

Cited by 58 publications

(45 citation statements)

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“…On induction of hemodynamic stress by pressure overload-induced hypertrophy, myofibroblasts increase in number (19,21). Because excessive accumulation of collagen in the cardiac interstitium is associated with pressure-overload hypertrophy, we speculate that myofibroblast conversion and the accompanying increase in collagenous ECM deposition by myofibroblasts contributes to increased amounts of collagen (24,42). Overdeposition of collagen in the heart has been associated with cardiac dysfunction, particularly in respect to relaxation of the ventricles during diastole (33,44).…”

Section: Discussionmentioning

confidence: 99%

Cardiac myofibroblasts differentiated in 3D culture exhibit distinct changes in collagen I production, processing, and matrix deposition

Poobalarahi¹,

Baicu²,

Bradshaw³

2006

American Journal of Physiology-Heart and Circulatory Physiology

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Myofibroblasts are a differentiated fibroblast cell type characterized by increased contractile capacity and elevated production of extracellular matrix (ECM) proteins. In the heart, myofibroblast expression is implicated in fibrosis associated with pressure-overload hypertrophy, among other pathologies. Although enhanced expression of ECM proteins by myofibroblasts is established, few studies have addressed the nature of the ECM deposited by myofibroblasts. To characterize ECM production and assembly by cardiac myofibroblasts, we developed a threedimensional (3D) culture system using primary cardiac fibroblasts seeded into a nylon mesh that allows us to reversibly interconvert between myofibroblast and fibroblast phenotypes. We report that an increase in collagen I production by myofibroblasts was accompanied by a significant increase in collagen deposition into insoluble ECM. Furthermore, myofibroblasts exhibited increased levels of procollagen ␣1(I) with C-propeptide attached (and N-propeptide removed) relative to procollagen ␣1(I) compared with fibroblast cultures. An increase in production of the myofibroblast-associated splice variant of fibronectin (EDA-Fn) was seen in myofibroblast 3D cultures. Because the regulation of procollagen I processing is known to have profound effects on ECM assembly, differences in procollagen I secretion and maturation coupled with expression of EDA-Fn are shown to contribute to the production of a distinct ECM by the cardiac myofibroblast.

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Section: Discussionmentioning

confidence: 99%

Cardiac myofibroblasts differentiated in 3D culture exhibit distinct changes in collagen I production, processing, and matrix deposition

Poobalarahi¹,

Baicu²,

Bradshaw³

2006

American Journal of Physiology-Heart and Circulatory Physiology

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“…Such myofibrillar loss would not, however, appear to be specific to MR, because it has been shown to be characteristic of failing myocardium in a variety of settings,61,62 including MR63 It is certainly not a morphological feature characteristic of volume-overload hypertrophy itself. 64 Rather, given that this ultrastructural feature has no relation to the degree of hypertrophy, as is seen in Figure 9, but rather relates well to the degree of ventricular and cellular contractile dysfunction, as is seen in Figure 8, …”

Section: Basis For Contractile Dysfunction In Mitral Regurgitationmentioning

confidence: 96%

Cellular and ventricular contractile dysfunction in experimental canine mitral regurgitation.

Urabe

Mann

Kent

et al. 1992

Circulation Research

135

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This study was designed to answer two questions. First, does the left ventricular contractile dysfunction resulting from mitral regurgitation (MR) reflect a primary defect in the cardiac muscle cell? Second, what is the basis for any change in cellular contractile function that might be observed? Left ventricular volume overload was produced in 10 dogs by catheter transection of mitral chordae tendineae. Three months later in these and in seven control dogs, left ventricular contractile function was characterized by the end-ejection stress-volume relation (EESVR). Investigators who were blinded to these results then characterized the contractile performance of cardiac muscle cells, or cardiocytes, from these same left ventricles in terms of the viscosity (graded external load)-velocity relation. Finally, the tissue and cellular components of these same left ventricles were analyzed morphometrically. Both the left ventricles from the MR group and their constituent cardiocytes showed marked contractile abnormalities. By matching ventricles with cells from the same MR dogs, ventricular EESVR was correlated with cardiocyte peak sarcomere shortening velocity (SSV). The correlation coefficient between EESVR and SSV was 0.63, but between a size-independent measure of active ventricular stiffness and SSV, it was 0.88. No change in left ventricular interstitial volume fraction was found in MR dogs, but both ventricular and cellular contractile dysfunction strongly correlated with a decreased volume fraction of cardiocyte myofibrils. Last, in an attempt to relate the degree of contractile dysfunction to the hypertrophic response, left ventricular mass in the MR dogs was correlated with both cellular and ventricular contractile indexes; no significant correlation was found. Three conclusions are warranted by these studies. First, chronic left ventricular volume overload from mitral regurgitation leads to contractile defects at both the ventricular and cellular levels, the extent of which correlates well in individual animals. Second, no quantitative interstitial change resulted from MR. Taken together, these two findings strongly suggest that the contractile defect is intrinsic to the cardiocyte. Third, while the contractile abnormality in MR remains undefined, the most basic defects appear to be a combination of myofibrillar loss with the failure of compensatory hypertrophy to occur in response to progressive decrements in cellular and ventricular function.

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“…Hypertrophy of the myocardium is produced by a global increase in protein synthesis that facilitates accumulation of myofibrils, mitochondria and other primary components of the cardiac muscle cell (cardiocyte) [3,4]. Translational mechanisms play a major role in accelerating the rate of protein synthesis in response to pressure overload by increasing the activity (efficiency) and amount (capacity) of the translation machinery, i.e., ribosomes and associated components such as eukaryotic initiation factors (eIFs) [5,6].…”

Section: Introductionmentioning

confidence: 99%

Selective translation of mRNAs in the left ventricular myocardium of the mouse in response to acute pressure overload

Spruill¹,

Baicu²,

Zile³

et al. 2008

Journal of Molecular and Cellular Cardiology

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During pressure overload hypertrophy, selective changes in cardiac gene expression occur that regulate growth and modify the structural and functional properties of the myocardium. To determine the role of translational mechanisms, a murine model of transverse aortic constriction was used to screen a set of specified mRNAs for changes in translational activity by measuring incorporation into polysomes in response to acute pressure overload. Candidate mRNAs were selected on the basis of two main criteria: 1) the 5′-untranslated region of the mRNA contains an excessive amount of secondary structure (ΔG < −50 kCal/mol), which is postulated to regulate efficiency of translation, and 2) the protein product has been implicated in the regulation of cardiac hypertrophy. After 24 hours of transverse aortic constriction, homogenates derived from the left ventricle were layered onto 15%-50% linear sucrose gradients and resolved into monosome fractions (messenger ribonucleoprotein particles) and polysome fractions by density gradient ultracentrifugation. The levels of mRNA in each fraction were quantified by real-time RT-PCR. The screen revealed that pressure overload increased translational activity of 6 candidate mRNAs as determined by a significant increase in the percentage of total mRNA incorporated into the polysome fractions. The mRNAs code for several functional classes of proteins linked to cardiac hypertrophy: the transcription factors c-myc, c-jun and MEF2D, growth factors VEGF and FGF-2, and the E3 ubiquitin ligase MDM2. These studies demonstrate that acute pressure overload alters cardiac gene expression by mechanisms that selectively regulate translational activity of specific mRNAs.

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Structural analysis of pressure versus volume overload hypertrophy of cat right ventricle

Cited by 58 publications

References 0 publications

Cardiac myofibroblasts differentiated in 3D culture exhibit distinct changes in collagen I production, processing, and matrix deposition

Cardiac myofibroblasts differentiated in 3D culture exhibit distinct changes in collagen I production, processing, and matrix deposition

Cellular and ventricular contractile dysfunction in experimental canine mitral regurgitation.

Selective translation of mRNAs in the left ventricular myocardium of the mouse in response to acute pressure overload

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