Pressure- and Volume-Induced Left Ventricular Hypertrophies Are Associated With Distinct Myocyte Phenotypes and Differential Induction of Peptide Growth Factor mRNAs

Calderone, Angelino; Takahashi, Nobuyuki; Izzo, Nicholas J.; Thaik, Cynthia M.; Colucci, Wilson S.

doi:10.1161/01.cir.92.9.2385

Cited by 154 publications

(98 citation statements)

References 37 publications

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“…In concentric LV hypertrophy, cardiomyocytes grow in a transverse direction while maintaining a constant cell length, whereas in eccentric hypertrophy, cardiomyocytes grow proportionally in longitudinal and transverse directions. This difference in cardiomyocyte remodeling correlates with distinct patterns of peptide growth factor induction in both conditions [9]. As shown in our studies, different correlation exists between cardiomyocyte hypertrophy and fibrosis in HFREF and HFREF patients [39].…”

Section: Cardiomyocyte Level: Structural and Functional Alterations Isupporting

confidence: 69%

Molecular determinants of heart failure with normal left ventricular ejection fraction

Borbély

Papp

Édes

et al. 2009

Pharmacological Reports

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Abstract:In population-based studies, heart failure with normal left ventricular (LV) ejection fraction (HFNEF) is now increasingly recognized and referred to as diastolic heart failure. However, the pathogenic mechanisms underlying HFNEF are incompletely understood, mainly because of limited availability of human myocardial biopsy material. Nevertheless, recent studies have examined in vivo hemodynamics, in vitro cardiomyocyte function, myofilamentary protein composition, collagen content and deposition of advanced glycation end products from LV endomyocardial biopsies. These measures were compared between HFNEF patients, subjects without symptoms of heart failure (controls), patients with heart failure and reduced ejection function (HFREF), and patients with HFNEF and HFREF with diabetes mellitus. This article summarizes the various findings of these studies and focuses on the possible correlations among altered LV myocardial structure, cardiomyocyte function, myofilamentary proteins, and extracellular matrices. These findings revealed novel mechanisms responsible for diastolic LV dysfunction, and they have important therapeutic implications, particularly HFNEF, for which a specific heart failure treatment strategy is largely lacking.

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Section: Cardiomyocyte Level: Structural and Functional Alterations Isupporting

confidence: 69%

Molecular determinants of heart failure with normal left ventricular ejection fraction

Borbély

Papp

Édes

et al. 2009

Pharmacological Reports

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“…Although the underlying mechanism by which E 2 prevented the increase of LVEDP remains undetermined, a role for nitric oxide may be postulated. In the myocardium, nitric oxide has been shown to increase diastolic distensibility (Prendergast et al, 1997;Paulus et al, 1994), and nitric oxide synthase activity in the heart can be enhanced by oestrogen treatment (Neudling et al, 1999) A sustained increase in systolic load, as observed in systemic hypertension leads to a concentric pattern of cardiac hypertrophy, characterized by the increased expression of the putative hypertrophic marker prepro-ANP mRNA and the progression of interstitial ®brosis (Boluyt & Bing, 1995;Calderone et al, 1995;Weber & Brilla, 1991;Grossman et al, 1975). Direct morphological examination was not performed to determine whether a concentric pattern of cardiac remodelling had occurred.…”

Section: Discussionmentioning

confidence: 99%

Elevated mean arterial pressure in the ovariectomized rat was normalized by ET_A receptor antagonist therapy: absence of cardiac hypertrophy and fibrosis

Mercier

Pham-Dang

Clement

et al. 2002

British J Pharmacology

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1 The in¯uence of menopause on ventricular function and remodelling remains unde®ned. The following study examined the e ect of ovariectomy on ventricular contractility, cardiac hypertrophy and extracellular matrix protein expression. 2 Elevated circulating levels of the vasoconstrictor endothelin-1 have been reported in postmenopausal women. Moreover, endothelin-1 has been shown to in¯uence blood pressure, ventricular function and cardiac remodelling. In this regard, the potential pathophysiological role of endothelin-1 in the ovariectomized rat was assessed via the administration of the selective endothelin A receptor (ET A ) antagonist BMS-182874.3 In 3 and 6 week ovariectomized female Sprague ± Dawley rats, uterus atrophy was associated with a signi®cant increase in mean arterial pressure, and left ventricular systolic pressure, as compared to sham. By contrast, right ventricular contractile indices were normal in the ovariectomized rat. Despite increased systolic load, left ventricular hypertrophy was not evident, prepro-atrial natriuretic peptide (prepro-ANP) mRNA levels and collagen protein content were similar to sham. 4 The treatment of ovariectomized rats with BMS-182874 (60 mg kg 71 per day) did not reverse uterus atrophy. However, BMS-182874 normalized mean arterial pressure, and left ventricular systolic pressure in the ovariectomized rat. 5 Thus, despite elevated blood pressure, ovariectomized rats were not associated with either cardiac hypertrophy or ®brosis. Lastly, endothelin-1, acting via the stimulation of the ET A receptor represents an integral mechanism implicated in the increase of mean arterial pressure following ovariectomy.

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“…130 Pressure and volume stress induce distinct molecular responses; despite a similar degree of hypertrophy and ANP induction, marked differences in the expression levels of ␤-myosin, ␣-skeletal actin, and SERCA2a were observed in pressure overload-induced hypertrophy relative to volume overload. 131 Taken together, hypertrophic signaling can be viewed as a web that integrates and modulates a multitude of input signals (Figure). Whereas multiple endogenous and exogenous inhibitors of cardiac hypertrophy have been identified, it will be critical to specifically target "pathological" hypertrophy while preserving the heart's ability to adapt to an increase in physiological demands.…”

Section: Physiological Versus Pathological Hypertrophymentioning

confidence: 99%

Hypertrophy of the Heart

et al. 2004

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Abstract-Recent studies call into question the necessity of hypertrophic growth of the heart as a "compensatory" response to hemodynamic stress. These findings, coupled with recent progress in dissecting the molecular bases of hypertrophy, raise the prospect of suppressing hypertrophy without provoking circulatory insufficiency. In this article, we focus on signaling pathways that hold promise as potential targets for therapeutic intervention. We also summarize observations from animal models and clinical trials that suggest benefit from an antihypertrophic strategy. Key Words: hypertrophy Ⅲ heart failure Ⅲ signal transduction C ardiac hypertrophy is an adaptive response to pressure or volume stress, mutations of sarcomeric (or other) proteins, or loss of contractile mass from prior infarction. Hypertrophic growth accompanies many forms of heart disease, including ischemic disease, hypertension, heart failure, and valvular disease. In these types of cardiac pathology, pressure overload-induced concentric hypertrophy is believed to have a compensatory function by diminishing wall stress and oxygen consumption. 1-3 At the same time, ventricular hypertrophy is associated with significantly increased risk of heart failure and malignant arrhythmia. 4,5 In the 1960s, Meerson and colleagues 6 divided hypertrophic transformation of the heart into 3 stages: (1) developing hypertrophy, in which load exceeds output, (2) compensatory hypertrophy, in which the workload/mass ratio is normalized and resting cardiac output is maintained, and (3) overt heart failure, with ventricular dilation and progressive declines in cardiac output despite continuous activation of the hypertrophic program. The late-phase "remodeling" process that leads to failure is associated with functional perturbations of cellular Ca 2ϩ homeostasis 7 and ionic currents, 8,9 which contribute to an adverse prognosis by predisposing to ventricular dysfunction and malignant arrhythmia. Significant morphological changes include increased rates of apoptosis, 10 fibrosis, and chamber dilation. Even though the dichotomy between adaptive and maladaptive hypertrophy has been appreciated for more than a century, 11 mechanisms that determine how long-standing hypertrophy ultimately progresses to overt heart failure are poorly understood.At the cellular level, cardiomyocyte hypertrophy is characterized by an increase in cell size, enhanced protein synthesis, and heightened organization of the sarcomere.Classically, 2 different hypertrophic phenotypes can be distinguished: (1) concentric hypertrophy due to pressure overload, which is characterized by parallel addition of sarcomeres and lateral growth of individual cardiomyocytes, and (2) eccentric hypertrophy due to volume overload or prior infarction, characterized by addition of sarcomeres in series and longitudinal cell growth. 12 At the molecular level, these changes in cellular phenotype are accompanied by reinduction of the so-called fetal gene program, because patterns of gene expression mimic those seen during ...

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Pressure- and Volume-Induced Left Ventricular Hypertrophies Are Associated With Distinct Myocyte Phenotypes and Differential Induction of Peptide Growth Factor mRNAs

Cited by 154 publications

References 37 publications

Molecular determinants of heart failure with normal left ventricular ejection fraction

Molecular determinants of heart failure with normal left ventricular ejection fraction

Elevated mean arterial pressure in the ovariectomized rat was normalized by ET_A receptor antagonist therapy: absence of cardiac hypertrophy and fibrosis

Hypertrophy of the Heart

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Pressure- and Volume-Induced Left Ventricular Hypertrophies Are Associated With Distinct Myocyte Phenotypes and Differential Induction of Peptide Growth Factor mRNAs

Cited by 154 publications

References 37 publications

Molecular determinants of heart failure with normal left ventricular ejection fraction

Molecular determinants of heart failure with normal left ventricular ejection fraction

Elevated mean arterial pressure in the ovariectomized rat was normalized by ETA receptor antagonist therapy: absence of cardiac hypertrophy and fibrosis

Hypertrophy of the Heart

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Resources

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Elevated mean arterial pressure in the ovariectomized rat was normalized by ET_A receptor antagonist therapy: absence of cardiac hypertrophy and fibrosis