FELIX JOSE ALVAREZ RAMIRES
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/11 - Laboratório de Cirurgia Cardiovascular e Fisiopatologia da Circulação, Hospital das Clínicas, Faculdade de Medicina
LIM/11 - Laboratório de Cirurgia Cardiovascular e Fisiopatologia da Circulação, Hospital das Clínicas, Faculdade de Medicina
12 resultados
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- Erythropoietin reduces collagen deposition after myocardial infarction but does not improve cardiac function(2018) PESSOA, Fernanda Gallinaro; MADY, Charles; FONSECA, Keila Cardoso Barbosa; OLIVEIRA-FONOFF, Adriana Morgan de; SALEMI, Vera Maria Cury; JORDAO, Mauricio Rodrigues; FERNANDES, Fabio; RAMIRES, Felix Jose AlvarezMyocardial remodeling includes inappropriate collagen deposition in the interstitium. Erythropoietin (EPO) may have cardioprotective effects. We aimed to assess the role of EPO on myocardial remodeling during the chronic phase. We studied 60 Wistar rats divided into the following groups: control (CT), control + EPO (CT + EPO), myocardial infarction + EPO (MI + EPO), and myocardial infarction (MI). The interstitial collagen volume fraction (ICVF) was quantified and echocardiography was performed. We quantified asymmetric dimethylarginine and glutathione by ELISA, and used real-time PCR to assess apoptosis and inflammation. Western blotting was used to evaluate inflammatory proteins and tissue inhibitors of metalloproteinases (TIMPs), and TUNEL staining was used to detect apoptosis. For matrix metalloproteinases (MMPs), we performed zymography. Parametric and nonparametric analyses were performed according to normality testing. ICVF was greater in MI groups (p < 0.001) and was attenuated by EPO (p = 0.05). The MMP-2 did not show any difference between groups. The TIMP-1 and TIMP-2 did not have difference between groups. The MI groups had worse fraction shortening (p < 0.001), without EPO protection (p = 0.666). The MI groups had increased left ventricle diastolic dimension (p < 0.001) without EPO attenuation (p = 0.79). EPO did not act on oxidative stress. Apoptosis and inflammation were not modulated by EPO. We concluded that EPO attenuated interstitial collagen accumulation, but did not protect from heart dilation or dysfunction.
conferenceObject Lack of Effect of Simvastatin on Structural Remodeling in Animal Model of Chagas Cardiomyopathy(2012) IANNI, Barbara M.; RAMIRES, Felix J. A.; SALEMI, Vera M. C.; FERNANDES, Fabio; OLIVEIRA, Adriana M.; PESSOA, Fernanda G.; FONSECA, Keila C. B.; ARTEAGA, Edmundo; NASTARI, Luciano; MADY, CharlesPurpose: Chagas cardiomyopathy(CM) is characterized by a large amount of fibrosis and inflamation. As simvastatin (simva) has anti-inflamatory effects, we hypothetized that it could be an important drug in the treatment of patients with CM. The purpose was to evaluate simva in the myocardium remodeling and inflammation in na animal model of CM. Methods: 123 hamsters were divided: C-controls(25), CSimva-controls with simva 10mg/Kg/day(25), Simva1-infected treated from beginning with the same dose of simva(25), Simva2-infected treated after 4 months(24); Infect-untreated(24). Follow-up of 10 months. Interstitial collagen volume fraction (ICVF) RV and LV measured using videomorphometry and picrosirius red stained heart. Metalloproteinase9 (MMP9) was obtained by zymography. Gene expression of TNFalpha, IFNgamma, IL10 by real time PCR and ΔCt. Survival by Kaplan-Meier and log rank. Comparison between groups by Kruskal-Wallis; p≤0.05. Results: Infected animals Simva1=189±133 days Simva2=150±124; Infect=138±123) lived less than controls (C=257±80; CSimva=283±58)(p≤0.05) with no difference among infected. ICVF-RV(%) was greater in infected groups (Simva1=3.88±1.14, Simva2=2.22±0.64; Infect=4.38±0.83) than in controls C=1.12±0.31; CSimva=2.18±0.73)(p≤0.05)with no difference among infected groups. ICVF-LV(%) was greater in infected animals (Simva1=1.83±1.01, Simva2=1.52±0.93; Infect=3.01±0.66) than in controls (C=0.68±0.31; CSimva=0.81±0.28)(p≤0.05) with no difference among infected. MMP9 was higher in infected groups (Simva1=2394±2441, Simva2=5673±4091; Infect=2392±2042) compared to controls (C=954±2332; CSimva=454±1123)(p≤0.05) with no difference among infected. TNFalpha did not have difference among infected groups (Simva1=5.33±3.66, Simva2=4.44±2.17; Infect=6.13±3.24). IFNgamma in infected groups (Simva1=5.47±3.56, Simva2=4.46±2.08; Infect=4.21±2.09) was higher than in controls (C=8.50±2.59; CSimva=6.84±2.53)(p≤0.05) with no difference among infected. IL10 in infected animals (Simva1=9.07±4.62, Simva2=7.76±4.77; Infect=8.11±4.48) did not have difference and the values were greater than controls (C=14.11±4.40; CSimva=12.55±3.90)(p≤0.05). Conclusions: Simva did not attenuate deposition of interstitial collagen, did not change dynamics of collagen degradation, did not decrease inflammation, and did not reduce mortality.conferenceObject Influence of air pollution upon myocardial remodeling(2013) OLIVEIRA, A. M.; RAMIRES, F.; FONSECA, K. C. B.; SALEMI, V. M.; PESSOA, F. G.; FERNANDES, F.; SALDIVA, P.; MADY, C.conferenceObject EFFECTS OF DIGITOXIN ON MYOCARDIAL COLLAGEN DEPOSITION IN AN EXPERIMENTAL FIBROSIS MODEL(2012) MADY, Charles; TAVARES, Leandro; RAMIRES, Felix; PESSOA, Fernanda; OLIVEIRA, Adriana; FERREIRA FILHO, Julio; FERNANDES, Fabio; SALEMI, VeraBackground Recent studies showed that digital compounds may regulate the interstitial collagen deposition. The objective of our study was to evaluate the role of the digital on myocardial fibrosis in an experimental model. Methods The sample was divided in 20 rats from the control group (CG); 20 rats submitted to an experimental model of fibrosis, in which the rats were uninefrectomized, drank water with 1% NaCl during the protocol and received aldosterone through an osmotic minipump (AG); and 20 rats submitted to the same experimental model were treated with digitoxin in a daily dose of 100 g/Kg (DAG). All animals were submitted to high resolution echocardiography at the beginning and the end of the study. Serum B-type natriuretic peptide (BNP) levels were measured by Elisa. After 6 weeks of treatment the animals were euthanized, Picrosirius Red stain was used to quantify myocardial collagen, and gelatin zymography was performed for metalloproteinases-2 and metalloproteinases-9 activity of the heart samples. Results The AG (1.4 ± 0.14 g) and DAG (1.25 ± 0.1 g) showed increased left ventricular mass compared to CG (1.13 ± 0.08 g; p=0.001) and relative wall thickness (AG: 0.68 ± 0.15 and DAG: 0.75 ± 0.22 vs CG: 0.47± 0.07; p=0.001) reflecting concentric hypertrophy by high resolution echocardiogram. The myocardial performance index showed a increased in AG (0.49 ± 0.08) compared to DAG (0.40 ± 0.13) and CG (0.32 ± 0.06; p=0.001), reflecting global myocardial dysfunction. The right and left ventricular interstitial and the perivascular collagen volume fraction showed a significant increase of AG compared to DAG and CG (p< 0.001). The BNP levels were increased in AG (1.07 ± 0.32 ng/ml) compared to DAG (0.84 ± 0.21 ng/ml) and CG (0.75 ± 0.19 ng/ml; p=0.01). The metalloproteinases levels did not differ among the groups. There was a positive correlation between fractional shortening and BNP levels of the GAD animals (r= 0.95; p= 0.0001). Conclusions These data demonstrate the digitoxin positive effect on the myocardial collagen deposition in this experimental model of interstitial fibrosis and could have a new therapeutic target previously unexplored. ACC Moderated Poster Contributions McCormick Place South, Hall A Monday, March 26, 2012, 11:00 a.m.-Noon Session Title: Alterations in Cardiac Morphology and Function Abstract Category: 15. Heart Failure: Basic Presentation Number: 1231-553- The effect of beta-blockade on myocardial remodelling in Chagas' cardiomyopathy(2012) PIMENTEL, Walace de Souza; RAMIRES, Felix Jose Alvarez; IANNI, Barbara Maria; SALEMI, Vera Maria Cury; BILATE, Angelina Morand Bianchi; CUNHA-NETO, Edecio; OLIVEIRA, Adriana Morgan de; FERNANDES, Fabio; MADY, CharlesOBJECTIVE: Chagas' disease has spread throughout Latin America because of the high rate of migration among these countries. Approximately 30% of Chagas' patients will develop cardiomyopathy, and 10% of these will develop severe cardiac damage leading to heart failure. Beta-blockade improves symptoms and survival in heart failure patients; however, its efficacy has not been well established in Chagas' disease. We evaluated the role of carvedilol in cardiac remodeling and mortality in a Chagas' cardiomyopathy animal model. METHODS: We studied Trypanosoma cruzi infection in 55 Syrian hamsters that were divided into three groups: control (15), infected (20), and infected + carvedilol (20). Animals underwent echocardiography, electrocardiography, and morphometry for collagen evaluation in ventricles stained with picrosirius red. RESULTS: The left ventricular diastolic diameter did not change between groups, although it was slightly larger in infected groups, as was left ventricular systolic diameter. Fractional shortening also did not change between groups, although it was slightly lower in infected groups. Collagen accumulation in the interstitial myocardial space was significantly higher in infected groups and was not attenuated by carvedilol. The same response was observed in the perivascular space. The survival curve showed significantly better survival in the control group compared with the infected groups; but no benefit of carvedilol was observed during the study. However, in the acute phase (up to 100 days of infection), carvedilol did reduce mortality. CONCLUSION: Carvedilol did not attenuate cardiac remodeling or mortality in this model of Chagas' cardiomyopathy. The treatment did improve survival in the acute phase of the disease.
- The role of air pollution in myocardial remodeling(2017) OLIVEIRA-FONOFF, A. M. de; MADY, C.; PESSOA, F. G.; FONSECA, K. C. B.; SALEMI, V. M. C.; FERNANDES, F.; SALDIVA, P. H. N.; RAMIRES, F. J. A.Background Excessive air pollution in urban environments can impact morbidity and mortality. The authors evaluated the role of particulate matter(2.5) (PM2.5) in structural, geometric, and functional remodeling in hearts, using an experimental model of myocardial infarction. Methods and findings Seventy-five rats were divided into 5 groups: control (CG), CG exposed to PM2.5 pollution (CGP), myocardial infarcted group (MI), infarcted group immediately exposed to pollution (IGP-I), and infarcted group previously exposed to pollution and kept exposed after infarction (IGP-II). Greater deposition of interstitial collagen occurred in the left ventricle in CGP, MI, IGP-I, and IGP-II groups compared with that in controls (p = 0.002 CG vs CGP and p<0.0001 CG vs MI, IGP-I, and IGP-II). In the right ventricle, greater collagen deposition existed in CGP, MI, IGP-I, and IGP-II compared with that in CG (p<0.021 CG vs CGP and p<0.0001 CG vs MI, IGP-I, and IGP-II). At the end of the study, CG had a higher mean shortening fraction than the other groups had (p <= 0.03). Left ventricular systolic diameter was lower in CG than in infarcted groups (p <= 0.003). The infarcted groups had greater expression of TGF-beta (p <= 0.04). PM2.5 increased the expression of TGF-beta in the IGP-II compared with the MI group (p = 0.004). The TNF-alpha gene was overexpressed in the IGP-II compared with the CGP group (p = 0.012). INF-gamma gene expression was greater in IGP-II (p <= 0.01). Oxidative stress analysis showed a higher glutathione concentration in CGP (p = 0.03), MI (p = 0.014), and IGP-I (p = 0.008) compared with that in CG. Conclusions PM2.5 stimulates the deposition of fibrosis in the myocardium of healthy hearts, but not in infarcted hearts. PM2.5 modulates the inflammatory response, which was greater in the IGP-II group. It also modulates oxidative stress in healthy hearts but not in infarcted hearts.
conferenceObject The role of erythropoieitin upon myocardial fibrosis(2014) PESSOA, FFernanda; RAMIRES, F.; FONSECA, K.; OLIVEIRA, A.; SALEMI, V.; FERNANDES, F.; MADY, C.conferenceObject The Role of Erythropoietin Upon Myocardial Fibrosis(2012) PESSOA, Fernanda G.; RAMIRES, Felix J. A.; FONOFF, Adriana M. O.; FONSECA, Keila C. B.; SALEMI, Vera M. C.; FERNANDES, Fabio; MADY, CharlesconferenceObject The Role of Air Pollution upon Myocardial Remodeling(2014) FONOFF, Adriana M. O.; RAMIRES, Felix Jose Alvarez; FONSECA, Keila Barbosa; SALEMI, Vera Maria Cury; PESSOA, Fernanda Gallinaro; SALDIVA, Paulo Hilario; MADY, Charles- Effect of Colchicine on Myocardial Injury Induced by Trypanosoma cruzi in Experimental Chagas Disease(2012) FERNANDES, Fabio; RAMIRES, Felix Jose Alvarez; IANNI, Barbara Maria; SALEMI, Vera Maria Cury; OLIVEIRA, Adriana Morgan; PESSOA, Fernanda Gallinaro; CANZIAN, Mauro; MADY, CharlesBackground: The hallmark of Chagas disease (CD) is multifocal myocarditis and extensive fibrosis. We investigated the potential effect of colchicine on myocardial remodeling in experimental CD. Methods and Results: One hundred Syrian hamsters were randomly divided into noninfected untreated control (CG), noninfected control treated with colchicine (COLG 0.4 mg kg(-1) d(-1) by gavage), infected (IG), and infected treated with colchicine (ICOLG, 0.4 mg kg(-1) d(-1)) groups. The interstitial collagen volume fraction (ICVF) was evaluated by videomorphometry with picrosirius red staining. The gelatinolytic activities of matrix metalloproteinase (MMP) 2 were examined with the use of zymography. Myocarditis was described according to the Dallas criteria. Statistical comparisons were performed with parametric analysis of variance and Tukey test. ICVF (%) accumulation was attenuated in infected colchicine-treated animals in the left (CG 0.81 +/- 0.13, COLG 0.85 +/- 0.13, IG: 1.35 +/- 0.31,* ICOLG 1.06 +/- 0.19; *P < .05 compared with ICOLG) and right ventricles (CG 1.4 +/- 0.36, COLG 1.26 +/- 0.14, IG 1.97 +/- 0.058,* ICOLG: 1.52 +/- 0.23; *P < .05 compared with ICOLG). A significant increase in MMP-2 enzymatic activity (UA) was observed in ICOLG (17,432.8*) compared with GC (3731.6), COLG (2,792.6), and IG (4,286.3; *P < .001). In IG, 66% of animals had myocarditis compared with only 49% in ICOLG. Conclusions: Colchicine had a protective effect on myocardium, indicated by decreased interstitial myocardial fibrosis, increased intensity of MMP-2, and attenuated myocardial inflammation. (J Cardiac Fail 2012;18:654-659)