Patterns of myocardial fibrosis*1

Weber, Karl T.; Pick, Ruth; Jalil, Jorge; Janicki, Joseph S.; Carroll, Eugenia P.

doi:10.1016/0022-2828(89)90778-5

Cited by 162 publications

(84 citation statements)

References 37 publications

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“…The concentric hypertrophy is a result of the increase of the myocytes' diameter with little or no change in the cellular size 26 . Concomitantly, there are changes in the proportions of myocardial interstitial components, including accumulation of collagen in ventricular musculature 27,28 . Stimulus to CR happens due to mechanical and biochemical factors that act on receptors, ion channels and integrins present in sarcolemal membrane which, by activating biochemical citosolic signalizers, trigger increase of protein synthesis and alterations in gene expression 2,12 .…”

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%

See 1 more Smart Citation

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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Section: Weeksmentioning

confidence: 99%

Section: Weeksmentioning

confidence: 99%

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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“…While both types of myocardial fibrosis result from a dysregulated collagen turnover (i.e. synthesis exceeds degradation, facilitating the deposition of highly cross‐linked, stiff, and degradation‐resistant collagen fibres)2, 3 impairing cardiac funtion,4 the excessive accumulation of collagen in the ECM may result from various altered signalling pathways 5. While fibrosis is essential for cardiac repair, its excessive and aberrant accumulation is deleterious; hence, there is a thin line separating ‘good’ from ‘bad’ fibrosis.…”

Section: Introductionmentioning

confidence: 99%

Rationale of the FIBROTARGETS study designed to identify novel biomarkers of myocardial fibrosis

et al. 2017

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AimsMyocardial fibrosis alters the cardiac architecture favouring the development of cardiac dysfunction, including arrhythmias and heart failure. Reducing myocardial fibrosis may improve outcomes through the targeted diagnosis and treatment of emerging fibrotic pathways. The European‐Commission‐funded ‘FIBROTARGETS’ is a multinational academic and industrial consortium with the main aims of (i) characterizing novel key mechanistic pathways involved in the metabolism of fibrillary collagen that may serve as biotargets, (ii) evaluating the potential anti‐fibrotic properties of novel or repurposed molecules interfering with the newly identified biotargets, and (iii) characterizing bioprofiles based on distinct mechanistic phenotypes involving the aforementioned biotargets. These pathways will be explored by performing a systematic and collaborative search for mechanisms and targets of myocardial fibrosis. These mechanisms will then be translated into individualized diagnostic tools and specific therapeutic pharmacological options for heart failure.Methods and resultsThe FIBROTARGETS consortium has merged data from 12 patient cohorts in a common database available to individual consortium partners. The database consists of >12 000 patients with a large spectrum of cardiovascular clinical phenotypes. It integrates community‐based population cohorts, cardiovascular risk cohorts, and heart failure cohorts.ConclusionsThe FIBROTARGETS biomarker programme is aimed at exploring fibrotic pathways allowing the bioprofiling of patients into specific ‘fibrotic’ phenotypes and identifying new therapeutic targets that will potentially enable the development of novel and tailored anti‐fibrotic therapies for heart failure.

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“…It is characterized by excessive accumulation of fibrillar collagen in the extracellular space, either because of a loss of cardiomyocytes (replacement fibrosis) and/or as an interstitial response to various chronic cardiovascular diseases such as hypertension, myocarditis, and congestive heart failure (reactive fibrosis). 1 In humans, cardiac fibrosis is universal in the aging heart. Activated fibroblasts play a pivotal role in the formation and maintenance of fibrous tissue by the production of various extracellularmatrix proteins, including collagen and fibronectin.…”

mentioning

confidence: 99%