Cellular changes in mechanically overloaded heart

Hatt, P. Y.

doi:10.1007/bf01906361

Cited by 19 publications

(5 citation statements)

References 10 publications

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“…At the fiber level, the growth of muscle cells is classically attributed to parallel or serial additions of sarcomeres [21][22][23], commonly referred to as concentric and eccentric hypertrophy [24,25], respectively. Concentric hypertrophy leads to wall thickening with small changes in the ventricle volume, whereas the eccentric hypertrophy induces volume dilation together with potential wall thinning through elongation of the free wall.…”

Section: Introductionmentioning

confidence: 99%

Interactions Between Structural Remodeling and Hypertrophy in the Right Ventricle in Response to Pulmonary Arterial Hypertension

Avazmohammadi¹,

Mendiola²,

Li³

et al. 2019

Journal of Biomechanical Engineering

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Pulmonary arterial hypertension (PAH) exerts substantial pressure overload on the right ventricle (RV), inducing RV remodeling and myocardial tissue adaptation often leading to right heart failure. The associated RV free wall (RVFW) adaptation involves myocardial hypertrophy, augmented intrinsic contractility, collagen fibrosis, and structural remodeling in an attempt to cope with pressure overload. If RVFW adaptation cannot maintain the RV stroke volume (SV), RV dilation will prevail as an exit mechanism, which usually decompensates RV function, leading to RV failure. Our knowledge of the factors determining the transition from the upper limit of RVFW adaptation to RV decompensation and the role of fiber remodeling events such as extracellular fibrosis and fiber reorientation in this transition remains very limited. Computational heart models that connect the growth and remodeling (G&R) events at the fiber and tissue levels with alterations in the organ-level function are essential to predict the temporal order and the compensatory level of the underlying mechanisms. In this work, building upon our recently developed rodent heart models (RHM) of PAH, we integrated mathematical models that describe volumetric growth of the RV and structural remodeling of the RVFW. The time-evolution of RV remodeling from control and post-PAH time points was simulated. The results suggest that the augmentation of the intrinsic contractility of myofibers, accompanied by an increase in passive stiffness of RVFW, is among the first remodeling events through which the RV strives to maintain the cardiac output. Interestingly, we found that the observed reorientation of the myofibers toward the longitudinal (apex-to-base) direction was a maladaptive mechanism that impaired the RVFW contractile pattern and advanced along with RV dilation at later stages of PAH. In fact, although individual fibers were more contractile post-PAH, the disruption in the optimal transmural fiber architecture compromised the effective contractile function of the RVFW, contributing to the depressed ejection fraction (EF) of the RV. Our findings clearly demonstrate the critical need for developing multiscale approaches that can model and delineate relationships between pathological alterations in cardiac function and underlying remodeling events across fiber, cellular, and molecular levels.

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Section: Introductionmentioning

confidence: 99%

Interactions Between Structural Remodeling and Hypertrophy in the Right Ventricle in Response to Pulmonary Arterial Hypertension

Avazmohammadi¹,

Mendiola²,

Li³

et al. 2019

Journal of Biomechanical Engineering

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“…This has been described in other types of overloaded hearts (9,10,11,26), but the metabolic significance of this feature is still unknown. This process seems to have a certain inertia: mitochondria do not stop proliferating after constriction is released.…”

Section: Discussionmentioning

confidence: 84%

Entwicklung und Rückbildung druckinduzierter Herzhypertrophie

et al. 1978

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Light and electron microscopy, combined with morphometry, were utilized to study myocardial cell modifications induced by a temporary abdominal aortic constriction in the rat. During the early stage of active hypertrophy, cell enlargement in the subendocardial layers of the left ventricle was predominant. This enlargement may be partly due to intracellular edema, characteristic of cell damage. Degenerative foci leading to fibrous scars were found primarily in the subendocardium and midwall layers. The times taken by the different cell structures to adapt to modifications of the load were rather different; some adapted very rapidly (nucleoli, intercalated discs), while others were much slower (cell diameter, mitochondria).

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“…ANF is normally constitutively secreted from the ventricular myocytes (Bloch et al 1988;, whereas in volume-overloaded hearts the synthesis and secretion is upregulated. Accordingly, increased levels of ANF mRNA are observed (Lattion et al 1986) and secretory granules similar to those seen in the atria occur (Hatt 1975;Takemura et al 1990;. Characteristically, the expression of ANF immunoreactivity is most significant in the regions close to the infarcted myocardium .…”

Section: Discussionmentioning

confidence: 88%

Regional activation of the immediate‐early response gene c‐fos in infarcted rat hearts

Larsen

Skar

Frotjold

et al. 1998

Int J Experimental Path

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Regional infarction of the left ventricle is followed by hypertrophy of the viable myocardium. This compensatory growth of cardiac myocytes requires induction of gene transcription and synthesis of proteins. In this study, we examined the expression of the immediate-early response gene c-fos following ligation of the left coronary artery in rat hearts. RNase protection assay demonstrated a rapid increase in the c-fos mRNA level in the ventricular myocardium. After two days of infarction, the c-fos expression was attenuated and was comparable to that observed in sham-operated control hearts. In situ tissue distribution of Fos protein-like immunoreactivity revealed the appearance of positively stained cells adjacent to the lateral border of the ischaemic myocardium, in the left ventricular subendocardial areas, in the papillary muscles of the left ventricle, in the proximity of great transmural vessels, and focally in the normo-perfused subepicardial myocardium. Double staining using antibodies recognizing the Fos protein and alpha-actinin, confirmed that the accumulation of nuclear Fos protein-like immunoreactivity was mainly seen in the cardiac myocytes. However, double staining of the Fos protein and Hoechst DNA labelling showed that detectable immunoreactivity occurred only in a limited proportion of the total nuclei present in these myocardial regions. Moreover, the regions showing c-fos activation correspond to the areas in which the appearance of subsequent growth responses are most pronounced following myocardial infarction. The present results therefore indicate that an early and regional c-fos activation is taking place in viable cardiac myocytes following left coronary artery ligation, and that c-fos is a possible regulating factor of sequential events leading to altered pattern of gene expression and protein synthesis in the hypertrophying heart.

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Cellular changes in mechanically overloaded heart

Cited by 19 publications

References 10 publications

Interactions Between Structural Remodeling and Hypertrophy in the Right Ventricle in Response to Pulmonary Arterial Hypertension

Interactions Between Structural Remodeling and Hypertrophy in the Right Ventricle in Response to Pulmonary Arterial Hypertension

Entwicklung und Rückbildung druckinduzierter Herzhypertrophie

Regional activation of the immediate‐early response gene c‐fos in infarcted rat hearts

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