Cardiac Remodeling: Concepts, Clinical Impact, Pathophysiological Mechanisms and Pharmacologic Treatment

Azevedo, Paulo Furquim de; Polegato, Bertha Furlan; Minicucci, Marcos F.; Paiva, Sérgio Alberto Rupp de; Zornoff, Leonardo A. M.

doi:10.5935/abc.20160005

Cited by 307 publications

(358 citation statements)

References 52 publications

Supporting

Mentioning

331

Contrasting

Unclassified

Order By: Relevance

“…It should be emphasized that although the remodeling is an extremely complex event, after the infarction this process is clinically recognized by an increase in the LV cavity. In addition, a well-accepted concept is that the remodeling process is usually associated with deterioration of ventricular function [2][3][4][5]. Therefore, our study suggests that zinc administration attenuated infarct-induced ventricular remodeling, associated with improved systolic and diastolic function.…”

Section: Discussionmentioning

confidence: 59%

“…In the acute phase, remodeling favors the formation of the aneurysm and predisposes the infarcted heart to ventricular rupture. Chronically, it is associated with a higher prevalence of malignant arrhythmias and ventricular dysfunction, as the noninfarcted region undergoes genetic, structural, and biochemical changes that will result in deterioration of the heart's functional capacity and death [1][2][3][4][5]. Therefore, strategies that attenuate remodeling result in improved postinfarction prognosis.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Zinc Supplementation Attenuates Cardiac Remodeling After Experimental Myocardial Infarction

Gonçalves¹,

Polegato²,

Fernandes³

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: The objective of our study was to evaluate the effects of zinc supplementation on cardiac remodeling following acute myocardial infarction in rats. Methods: Animals were subdivided into 4 groups and observed for 3 months: 1) Sham Control; 2) Sham Zinc: Sham animals receiving zinc supplementation; 3) Infarction Control; 4) Infarction Zinc. After the followup period, we studied hypertrophy and ventricular geometry, functional alterations in vivo and in vitro, changes related to collagen, oxidative stress, and inflammation, assessed by echocardiogram, isolated heart study, western blot, flow cytometer, morphometry, and spectrophotometry. Results: Infarction induced a significant worsening of the functional variables. On the other hand, zinc attenuated both systolic and diastolic cardiac dysfunction induced by infarction. Considering the infarct size, there was no difference between the groups. Catalase and superoxide dismutase decreased in infarcted animals, and zinc increased its activity. We found higher expression of collagens I and III in infarcted animals, but there was no effect of zinc supplementation. Likewise, infarcted animals had higher levels of IL-10, but without zinc interference. Nrf-2 values were not different among the groups. Infarction increased the amount of Treg cells in the spleen as well as the amount of total lymphocytes. Zinc increased the amount of CD4+ in infarcted animals, but we did not observe effects in relation to Treg cells. Conclusion: zinc attenuates cardiac remodeling after infarction in rats; this effect is associated with modulation of antioxidant enzymes, but without the involvement of collagens I and III, Nrf-2, IL-10, and Treg cells.

show abstract

Section: Discussionmentioning

confidence: 59%

Section: Introductionmentioning

confidence: 99%

Zinc Supplementation Attenuates Cardiac Remodeling After Experimental Myocardial Infarction

Gonçalves¹,

Polegato²,

Fernandes³

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

show abstract

“…Our results demonstrated that RA, added to a normal rat chow diet, induced myocardial hypertrophy, as assessed by CSA. Regardless of the complexity of the remodeling process, it is well established that myocardium hypertrophy plays a key role on cardiac remodeling [28]. Interestingly, LV function was preserved with the treatment.…”

Section: Discussionmentioning

confidence: 91%

Cardiac Remodeling Induced by All-Trans Retinoic Acid is Detrimental in Normal Rats

Silva¹,

Gonçalves²,

Santos³

et al. 2017

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: This study aimed to discern whether the cardiac alterations caused by retinoic acid (RA) in normal adult rats are physiologic or pathologic. Methods and Results: Wistar rats were assigned into four groups: control animals (C, n = 20) received a standard rat chow; animals fed a diet supplemented with 0.3 mg/kg/day all-trans-RA (AR1, n = 20); animals fed a diet supplemented with 5 mg/kg/day all-trans-RA (AR2, n = 20); and animals fed a diet supplemented with 10 mg/kg/day all-trans-RA (AR3, n = 20). After 2 months, the animals were submitted to echocardiogram, isolated heart study, histology, energy metabolism status, oxidative stress condition, and the signaling pathway involved in the cardiac remodeling induced by RA. RA increased myocyte cross-sectional area in a dose-dependent manner. The treatment did not change the morphological and functional variables, assessed by echocardiogram and isolated heart study. In contrast, RA changed catalases, superoxide dismutase, and glutathione peroxidases and was associated with increased values of lipid hydroperoxide, suggesting oxidative stress. RA also reduced citrate synthase, enzymatic mitochondrial complex II, ATP synthase, and enzymes of fatty acid metabolism and was associated with increased enzymes involved in glucose use. In addition, RA increased JNK 1/2 expression, without changes in TGF-β, PI3K, AKT, NFκB, S6K, and ERK. Conclusion: In normal rats, RA induces cardiac hypertrophy in a dose-dependent manner. The non-participation of the PI3K/Akt pathway, associated with the participation of the JNK pathway, oxidative stress, and changes in energy metabolism, suggests that cardiac remodeling induced by RA supplementation is deleterious.

show abstract

“…Transverse aortic constriction (TAC) in mice or rats is the most commonly used experimental method of modelling cardiac hypertrophy and fibrosis in animals . Currently employed treatments for patients with cardiac hypertrophy include calcium channel blockers, beta blockers, angiotensin‐converting enzyme inhibitors, angiotensin II receptor blockers, and diuretics …”

Section: Introductionmentioning

confidence: 99%

Gentisic acid attenuates pressure overload‐induced cardiac hypertrophy and fibrosis in mice through inhibition of the ERK1/2 pathway

Sun

Kee

Jin

et al. 2018

J Cellular Molecular Medi

View full text Add to dashboard Cite

We previously reported that gentisic acid (2,5‐dihydroxybenzoic acid) is the third most abundant phenolic component of Dendropanax morbifera branch extracts. Here, we investigated its effects on cardiac hypertrophy and fibrosis in a mouse model of pressure overload and compared them to those of the beta blocker bisoprolol and calcium channel blocker diltiazem. Cardiac hypertrophy was induced in mice by transverse aortic constriction (TAC). Beginning 2 weeks after this procedure, the mice were given daily intraperitoneal injections of gentisic acid (100 mg/kg/d), bisoprolol (5 mg/kg/d) or diltiazem (10 mg/kg/d) for 3 weeks. Cardiac hypertrophy was evaluated by the heart weight‐to‐body weight ratio, the cardiomyocyte cross‐sectional area after haematoxylin and eosin staining, and echocardiography. Markers of cardiac hypertrophy and fibrosis were tested by reverse transcription‐quantitative real‐time polymerase chain reaction, western blotting and Masson's trichrome staining. The suppressive effects of gentisic acid treatment on TAC‐induced cardiac hypertrophy and fibrosis were comparable to those of bisoprolol administration. Cardiac hypertrophy was reversed and left ventricular septum and posterior wall thickness were restored by gentisic acid, bisoprolol and diltiazem treatment. Cardiac hypertrophic marker gene expression and atrial and brain natriuretic peptide levels were decreased by gentisic acid and bisoprolol, as were cardiac (interstitial and perivascular) fibrosis and fibrosis‐related gene expression. Cardiac hypertrophy‐associated upregulation of the transcription factors GATA4 and Sp1 and activation of extracellular signal‐regulated kinase 1/2 were also negated by these drugs. These results suggest that gentisic acid could serve as a therapeutic agent for cardiac hypertrophy and fibrosis.

show abstract

Cardiac Remodeling: Concepts, Clinical Impact, Pathophysiological Mechanisms and Pharmacologic Treatment

Cited by 307 publications

References 52 publications

Zinc Supplementation Attenuates Cardiac Remodeling After Experimental Myocardial Infarction

Zinc Supplementation Attenuates Cardiac Remodeling After Experimental Myocardial Infarction

Cardiac Remodeling Induced by All-Trans Retinoic Acid is Detrimental in Normal Rats

Gentisic acid attenuates pressure overload‐induced cardiac hypertrophy and fibrosis in mice through inhibition of the ERK1/2 pathway

Contact Info

Product

Resources

About