Alterations in cardiac gene expression during the transition from stable hypertrophy to heart failure. Marked upregulation of genes encoding extracellular matrix components.

Boluyt, Marvin O.; O’Neill, Lydia; Meredith, Andrea L.; Bing, O.; Brooks, Wesley W.; Conrad, Chester H.; Crow, Michael T.; Lakatta, Edward G.

doi:10.1161/01.res.75.1.23

Cited by 302 publications

(209 citation statements)

References 56 publications

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“…The diastolic function was assessed by E-waves and A, ratio between E-waves and A-wave (E/A), E-wave deceleration times (WDT) and the LV isovolumetric relaxation time (LV-IVRT) 15,16 .…”

Section: Echocardiographic Assessmentmentioning

confidence: 99%

“…Improvement of systolic function in the SVASG versus the CG must be linked to the development of concentric hypertrophy, normalization of systolic tension and maintenance of physiological limits of oxygen consumption of myocardial fibers 2,16,19,29 . Progressive loss of systolic function may be connected with: 1) adverse geometrical remodeling of the cavity 30,31 ; 2) alterations in the composition of the heart muscle, with increase of the extracellular matrix and decrease in the number of myocytes, due to necrosis or apoptosis 16,31 ; 3) compromising of the capacity to contract 32 or 4) the combination of these factors 2,19,28 .…”

Section: Weeksmentioning

confidence: 99%

“…Progressive loss of systolic function may be connected with: 1) adverse geometrical remodeling of the cavity 30,31 ; 2) alterations in the composition of the heart muscle, with increase of the extracellular matrix and decrease in the number of myocytes, due to necrosis or apoptosis 16,31 ; 3) compromising of the capacity to contract 32 or 4) the combination of these factors 2,19,28 .…”

Section: Weeksmentioning

confidence: 99%

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Remodelamento cardíaco: análise seriada e índices de detecção precoce de disfunção ventricular

Mendes¹,

Campos²,

Damatto³

et al. 2010

Arq. Bras. Cardiol.

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Background: Supravalvar aortic stenosis (SVAS) is used to study overload-induced cardiac remodeling (CR). In this model, neither CR behavior since beginning stage nor the best parameters to identify ventricular dysfunction are clearly stated.Objective: ) Characterizing, early and evolutively, morphological and functional modifications during CR in rats with SVAS and ) identifying the most sensitive index for detecting the moment when the diastolic and systolic dysfunction first appeared in the left ventricle (LV). Methods IntroductionCardiac remodeling (CR) refers to an alteration in gene expression in response to an aggression, resulting in molecular changes, cellular changes and myocardial interstitial alterations, expressed in variations of the heart size, shape and function 1 . This is also a mechanism in adaptation to hemodynamic overload, allowing the heart to keep its functions in view of load increase 2-4 . This is deemed as a risk factor for development of ventricular dysfunction and heart failure (HF) 5 .Several experimental models have been proposed for the study of CR due to pressure overload, such as supravalvar aortic stenosis (SVAS) in rats [6][7][8] . When young animals are subject to aortic constriction, pressure overload is low at the beginning, being increased proportionally with their growth. SVAS advantages are: gradual development of CR, associated in short term to the improvement of systolic function; absence of severe lesions in myocardial anatomy; and low maintenance cost 9 . Around the 20 th week of SVAS, deterioration of systolic performance and HF [10][11][12][13] begin. This model is partially similar to SVAS in men 11 .Experiments in our lab with rats with SVAS assessed morphological and functional cardiac aspects, by means of echocardiogram (ECHO), in different periods of CR, finding out supranormal systolic function in 6 th or 8 th week 4,9,12 , diastolic dysfunction as of the 12nd week 9 and deterioration of systolic performance in the 21 st week. This last group of animals also had signs of heart failure 9 . Some authors, using hemodynamic evaluation, verified increase in left ventricular end-diastolic pressure after the 6 th week -in contrast, evaluation of diastolic function by means of ECHO has been found inaltered 13 . Litwin et al 8 assessed rats with SVAS by means of ECHO during 6 th , 12 th and 18 th weeks, and observed diastolic dysfunction as of the 6 th week and deterioration of systolic performance in the 18 th week.Analysis of mentioned studies has shows controversial results and absence of evaluation in an earlier post-induction of SVAS. The study aimed at characterizing, early and evolutively, Original ArticleArq Bras Cardiol 2010; 94(1) : 59-66

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“…The diastolic function was assessed by E-waves and A, ratio between E-waves and A-wave (E/A), E-wave deceleration times (WDT) and the LV isovolumetric relaxation time (LV-IVRT) 15,16 .…”

Section: Echocardiographic Assessmentmentioning

confidence: 99%

Section: Weeksmentioning

confidence: 99%

Section: Weeksmentioning

confidence: 99%

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Remodelamento cardíaco: análise seriada e índices de detecção precoce de disfunção ventricular

Mendes¹,

Campos²,

Damatto³

et al. 2010

Arq. Bras. Cardiol.

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“…It has been documented that concentric hypertrophy occurs in SHR between 6 and 12 mo of age, decompensating to heart failure near 15 mo (15,38). We chose to study these animals at 7 mo of age because cardiac function is well maintained and fibrosis is minimal (7). There are several design considerations that may affect the interpretability of the present study.…”

Section: Increased [Ca 2ϩmentioning

confidence: 99%

Effects of forskolin on inotropic performance and phospholamban phosphorylation in exercise-trained hypertensive myocardium

Kolwicz

Kubo

MacDonnell

et al. 2007

Journal of Applied Physiology

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responsiveness is downregulated in left ventricular (LV) hypertrophy induced by chronic hypertension. While exercise training in hypertension enhances ␤-AR responsiveness, the role of adenylyl cyclase remains unclear. The purpose of the present study was to test whether treadmill running in the spontaneously hypertensive rat (SHR) model improves LV responsiveness to forskolin (FOR) or the combination of FOR ϩ isoproterenol (FORϩISO). Female SHR (16-wk) were randomly placed into sedentary (SHR-SED; n ϭ 7) or treadmill-trained (SHR-TRD; n ϭ 8) groups. Wistar-Kyoto (WKY; n ϭ 7) animals acted as normotensive controls. Langendorff, isovolumic LV performance was established at baseline and during incremental FOR infusion (1 and 5 mol/l) and FORϩISO (5 mol/l ϩ 1ϫ10 Ϫ8 mol/l). Heart rate, systolic blood pressure, and heart-to-body weight ratio were lower in WKY relative to both SHR groups (P Ͻ 0.05). LV performance and heart rate significantly increased in all groups to a similar extent with incremental FOR infusion. However, in the presence of 5 mol/l FOR, ISO increased LV developed pressure, positive change in LV pressure, and negative change in LV pressure to a greater extent in SHR-TRD relative to SHR-SED (P Ͻ 0.05). Phospholamban phosphorylation at the Thr 17 was greater in SHR-TRD relative to SHR-SED and WKY (P Ͻ 0.05). Absolute LV developed pressure was moderately correlated with phospholamban phosphorylation at both the Ser 16 (r ϭ 0.64; P Ͻ 0.05) and Thr 17 (r ϭ 0.52; P Ͻ 0.05). Our data suggest that the adenylyl cyclase step in the ␤-AR cascade is not downregulated in the early course of hypertension and that the enhanced ␤-AR responsiveness with training is likely mediated at levels other than adenylyl cyclase. Our data also suggest that ␤-AR inotropic responsiveness in the presence of direct adenylyl cyclase agonism is improved in trained compared with sedentary SHR hearts.heart; hypertrophy; diastole; proteins; spontaneously hypertensive rat THE ␤-ADRENERGIC RECEPTOR (␤-AR) system is an integral pathway in regulating myocardial inotropy and lusitropy, particularly during the stress of exercise (43,46,51). With hypertension, however, the ␤-AR system is downregulated via receptor uncoupling (10, 27) and is clearly one hallmark of the maladaptive phenotype associated with compensatory hypertrophy (50). Recent data from our laboratory have shown that exercise training improves ␤-AR responsiveness in the spontaneously hypertensive rat (SHR) model by mitigating the left ventricular (LV) abundance of the ␤-AR receptor desensitizing kinase, G protein receptor kinase 2 (GRK2) (27). As a result of "restored" ␤-AR signaling, PKA-mediated phosphorylation of key sarcoplasmic reticulum (SR) Ca 2ϩ handling proteins, such as the ryanodine receptor and phospholamban (PLB), were improved with training (27). However, given that direct adenylyl cyclase/cAMP signaling may also be altered with hypertension (9, 28, 31), it remains unclear from our previous work whether "downstream-associated" ␤-AR mechanisms are likewise improved...

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“…O entendimento da etiopatogenia e fisiopatologia da disfunção diastólica isolada ou em associação com disfunção sistólica está bem fundamentado. Após dano miocárdico, ocorre um processo reparativo, onde se observa acúmulo de coláge-no, formando áreas fibróticas e que levam a uma diminuição da complacência ventricular 68,69 . Outra causa importante de disfunção ventricular inclui a hipertrofia que acompanha situações de sobrecarga de pressão, que depende da ação da aldosterona no miocárdio 70 .…”

Section: Paradigmas Atuaisunclassified

Em busca de novos paradigmas para o manejo da insuficiência cardíaca

Clausell¹,

Ribeiro²

1998

Arq. Bras. Cardiol.

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Estado da ArteConforme dados do Serviço Único de Saúde referentes ao ano de 1996 (Ministério da Saúde -Secretaria Executiva -DATASUS), as doenças cardiovasculares são responsá-veis por 16% do custo das internações hospitalares no Brasil, representando um custo anual de quase 500 milhões de reais. Deste valor, quase 150 milhões de reais foram destinados ao pagamento de internações hospitalares por insuficiência cardíaca (IC), sendo esta a causa mais freqüente de internações por doenças cardiovasculares. Portanto, no Brasil, medidas que pudessem reduzir o número de internações por IC teriam imenso impacto social.O manejo moderno da IC está bem definido na literatura 1,2 e parece seguir diversos paradigmas ou modelos que servem como exemplos de condutas. Seguindo a mesma abordagem por nós adotada para a cardiopatia isquêmica 3 , um paradigma de ação médica é baseado num conceito fisiopatológico, dispõe de um método diagnóstico confiá-vel e que permite estimar prognóstico, resultando em terapêutica capaz de controlar sintomas, diminuir morbidade e, preferencialmente, aumentar a sobrevida. Na 1ª parte deste artigo, apresentaremos, de forma didática, os paradigmas que têm orientado o manejo da IC nas últimas décadas (quadro I), discutindo suas limitações. Na 2ª parte, discutiremos alguns paradigmas que, no futuro breve, poderão melhorar o manejo desta síndrome. Finalmente, contrastaremos o manejo da IC baseado puramente no raciocínio clínico com aquele baseado na farmacologia clínica.

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Alterations in cardiac gene expression during the transition from stable hypertrophy to heart failure. Marked upregulation of genes encoding extracellular matrix components.

Cited by 302 publications

References 56 publications

Remodelamento cardíaco: análise seriada e índices de detecção precoce de disfunção ventricular

Remodelamento cardíaco: análise seriada e índices de detecção precoce de disfunção ventricular

Effects of forskolin on inotropic performance and phospholamban phosphorylation in exercise-trained hypertensive myocardium

Em busca de novos paradigmas para o manejo da insuficiência cardíaca

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