Abstract 220: Induction of Heme Oxygenase-1 Enhances Matrix Metalloproteinase-9 Secretion and Myocardial Fibrosis

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Muneyoshi Okada ◽  
Shiro Ikeda ◽  
Hideyuki Yamawaki ◽  
Yukio Hara
Keyword(s):  
Carbon Monoxide ◽  
Matrix Metalloproteinase ◽  
Myocardial Fibrosis ◽  
Heme Oxygenase ◽  
Cardiac Remodeling ◽  
Wistar Rats ◽  
Cardiac Fibroblasts ◽  
Ros Generation ◽  
Free Iron ◽  
Male Wistar Rats

Background: Heme oxygenase (HO)-1 is a stress-inducible rate-limiting enzyme in heme catabolism into carbon monoxide, biliverdin and free iron. Whereas HO-1 exerts cardioprotective effect, such as anti-hypertrophic and anti-apoptotic effect in cardiomyocytes, the influence of HO-1 on cardiac fibroblasts has not been clarified. We examined the effect of HO-1 induced by cobalt protoporphyrin IX (CoPPIX) on matrix metalloproteinase (MMP)-9 secretion, a biomarker of cardiac remodeling, in cardiac fibroblasts. Methods and Results: Cardiac fibroblasts were isolated from male Wistar rats. Secreted MMP-9 protein into culture medium and HO-1 expression in cell lysates were measured by Western blotting. CoPPIX (0.1-1 μ M) increased HO-1 expression and enhanced interleukin (IL)-1β (4 ng/ml, 24 h)-induced MMP-9 secretion (n=4). Mn 2 (CO) 10 (0.3-10 μ M), a carbon monoxide donor, increased IL-1β-induced MMP-9 secretion (n=4), although bilirubin (0.3-10 μ M), a metabolite of biliverdin, and FeSO 4 (0.3-10 μ M), a free iron donor, had no effect. Mn 2 (CO) 10 increased reactive oxygen species (ROS) generation and the enhanced effect of Mn 2 (CO) 10 on IL-1β-induced MMP-9 secretion was abolished by an antioxidant EUK-134 (10 μ M, n=4). We also examined the effect of CoPPIX on isoproterenol (5 mg/kg/day, subcutaneous injection, for 1 or 7 days)-induced cardiac remodeling in male Wistar rats. CoPPIX (1 mg/kg) was administered intraperitoneally every 2 days and this treatment increased HO-1 expression. Hearts were excised at the day 2 or day 8. Myocardial fibrosis was evaluated by Azan staining. At the day 8, CoPPIX worsened isoproterenol-induced myocardial fibrosis significantly (n=6), but had no effect on the increase of heart weight. CoPPIX also enhanced isoproterenol-induced MMP-9 expression at the day 2 (n=10). Conclusion: Induction of HO-1 by CoPPIX enhances IL-1β-induced MMP-9 secretion via ROS generation through heme-derived carbon monoxide in cardiac fibroblasts and isoproterenol-induced myocardial fibrosis and MMP-9 expression. These findings suggest that HO-1 induction does not necessarily exert cardioprotective effects.

scholarly journals Effect of Caffeic Acid Phenethyl Ester Provision on Fibroblast Growth Factor-2, Matrix Metalloproteinase-9 Expression, Osteoclast and Osteoblast Numbers during Experimental Tooth Movement in Wistar Rats (Rattus norvegicus)

2021 ◽  
Author(s):  
Ida Bagus Narmada ◽  
Paristyawati Dwi Putri ◽  
Lucky Lucynda ◽  
Ari Triwardhani ◽  
I Gusti Aju Wahju Ardani ◽  
...  
Keyword(s):  
Growth Factor ◽  
Matrix Metalloproteinase ◽  
Rattus Norvegicus ◽  
Wistar Rats ◽  
Tooth Movement ◽  
Caffeic Acid Phenethyl Ester ◽  
Fibroblast Growth Factor 2 ◽  
Fibroblast Growth ◽  
Male Wistar Rats ◽  
Metalloproteinase 9

Abstract Objectives To investigate the effect of caffeic acid phenethyl ester (CAPE) provision on matrix metalloproteinase-9 (MMP-9), fibroblast growth factor-2 (FGF-2) expression, osteoclast and osteoblast numbers during experimental orthodontic tooth movement (OTM) in male Wistar rats (Rattus norvegicus). Materials and Methods Forty-eight healthy male Wistar rats (R. norvegicus), 16 to 20 weeks old with 200 to 250 g body weight (bw) were divided into several groups as follows: K1: OTM for 3 days; K2: OTM for 7 days; K3: OTM for 14 days; KP1: OTM and CAPE for 3 days; KP2: OTM and CAPE for 7 days; and KP3: OTM and CAPE for 14 days. A nickel titanium closed coil spring 8.0 mm long with 10 g/mm2 was installed between the upper left first molar and upper central incisor to move molar mesially. CAPE provision with a dose of 20 mg/kg bw of animal studies was done per orally. Immunohistochemistry was done to examine MMP-9 expression and osteoclast number in compression side as well as FGF-2 expression and osteoblast number in tensile side of the OTM. Statistical Analysis One-way analysis of variance test and Tukey’s honest significant difference test were performed to determine the difference between the groups (p < 0.05). Results MMP-9 expression and osteoclast numbers in the compression side were significantly different between the groups. Similarly, FGF-2 expression and osteoclast numbers in the tensile side were significantly different between the groups. Conclusions CAPE provision during OTM increases the number of osteoblasts and the FGF-2 expression significantly in the tensile side. Osteoclast numbers and MMP-9 expression significantly decrease in the compression side.

Abstract 172: Lumican-null Mice Are Susceptible to Aging and Isoproterenol-induced Myocardial Fibrosis

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Pao-Hsien Chu
Keyword(s):  
Matrix Metalloproteinase ◽  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Myocardial Fibrosis ◽  
Cardiac Remodeling ◽  
Cardiac Fibrosis ◽  
Systolic Function ◽  
Wild Type ◽  
Matrix Metalloproteinase 1 ◽  
Membrane Type

Aims: With aging and stresses, the myocardium undergoes structural remodeling and often leading to fibrosis. Main Methods: To examine whether lumican, one of the class II small leucine-rich proteoglycans, has a role in cardiac remodeling and fibrosis, we analyzed the basic cardiac phenotypes of lumican-null (Lum-/-) mice in both youth and elder, and then used the isoproterenol-induced cardiac fibrosis model to study the roles of extra-cellular matrix and apoptosis in cardiac remodeling. Key Findings: Higher mortality resulted from significantly impaired systolic function, and an increase of atrial natriuretic peptide secreted by the ventricles in response to excessive stretching of myocytes of Lum-/- mice in comparison to wild type littermates. In addition, Lum-/- mice exhibited higher level of TGF-β, collagen I/III, and membrane-type matrix metalloproteinase-1 (MT1-MMP, or MMP-14) during cardiac remodeling. Significance: Our data implicates that the lumican protein plays an important role in the pathogenesis of cardiac fibrosis.

Abstract 242: Cardiac Remodeling Induced by Chronic β-Adrenergic Simulation Is Blocked by Myocyte-TGF-β Signaling

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Norimichi Koitabashi ◽  
Masahiko Kurabayashi ◽  
Eiki Takimoto ◽  
David A Kass
Keyword(s):  
Myocardial Fibrosis ◽  
Transforming Growth Factor Beta ◽  
Cardiac Remodeling ◽  
Transforming Growth Factor ◽  
Cardiac Fibroblasts ◽  
Hypertensive Heart Disease ◽  
Pressure Overload ◽  
Specific Gene ◽  
Tgfβ Signaling

[Background] Emerging evidence from cell-specific conditional gene manipulation models has revealed complex interactions with differential roles of cardiomyocyte (CM) and non-CM signaling in the evolution of pathological cardiac remodeling. A major factor involved in such cross talk is transforming growth factor-beta (TGFβ), which exists in CM,fibroblasts, and vascular cells. Both mechanical overload and prolonged catecholamine stimulation are critical determinants of hypertensive heart disease. Here, we tested the role of cell-specific TGFβ signaling in chronic pressure-overload or isoproterenol (Iso)-induced cardiac remodeling using CM-specific gene suppression of TGFβ type2 receptor in mice. [Methods and Results] αMHC-driven tamoxifen-inducible Cre (MCM) x Tgfbr2 floxed mice (MCMR2), which achieved CM-specific knockdown of TGFβ signaling, showed a striking suppression of cardiac dilatation and dysfunction induced by chronic pressure-overload. Chronic Iso infusion induced modest cardiac hypertrophy with moderate myocardial fibrosis. Interestingly, in contrast to TAC, myocardial fibrosis induced by the chronic Iso exposure was not inhibited, rather worsened in MCMR2 mice. Systemic treatment with TGFβ neutralizing antibody (NAb) for Chronic Iso significantly inhibited myocardial fibrosis, yet cardiac function and hypertrophy were not improved. In Iso-treated cultured cardiomyocytes, profibrotic genes were up-regulated by TGFβ-receptor inhibition, while they were inhibited in cultured cardiac fibroblasts. [Conclusion] CM-specific TGFβ signaling inhibition has marked protective effect for pressure-overload induced cardiac remodeling but not for Iso-induced cardiac remodeling. These results suggest that the role of TGFβ signaling may be determined by targeted cell types and pathological stresses in a development of heart failure.

Abstract 311: Inhibition Of Matrix Metalloproteinase-13 Dependent Protease-activated Receptor-1 Activation Attenuates Fibrotic Signaling

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Allison E Dixon ◽  
Fabrice Jaffre ◽  
Nigel Mackman ◽  
Burns C Blaxall
Keyword(s):  
Matrix Metalloproteinase ◽  
Cardiac Remodeling ◽  
Cardiac Fibroblasts ◽  
The United States ◽  
Matrix Metalloproteinase 13 ◽  
Ecm Proteins ◽  
Excess Production ◽  
Potential Therapeutic Role ◽  
Protease Activated Receptor 1

Heart failure (HF) is the leading cause of morbidity and mortality in the United States and is characterized by progressive myocardial fibrosis, pathologic remodeling and deteriorating cardiac function. Cardiac fibroblasts (CF) are largely responsible for the secretion of ECM proteins as well as cytokines and growth factors in the heart. Upon injury or pathologic stimulation, CF transition to a myofibroblast phenotype, leading to excess production of ECM proteins and pro-inflammatory cytokines. Previous studies in our lab have indicated a role for protease-activated receptor-1 (PAR-1), the most highly expressed GPCR on CF, in pathologic cardiac remodeling. In particular, we reported the novel cleavage of PAR-1 via matrix metalloproteinase-13 (MMP-13) and cardioprotective effects of MMP-13 inhibition in an acute model of HF. Therefore, we hypothesize that MMP-13 plays an important role in cardiac remodeling through activation of PAR-1, particularly in the pathologic transition of CF to myofibroblasts. To investigate this hypothesis, RNA was collected from hearts of mice infused with isoproterenol (ISO) for 7 days and concurrently treated with a specific MMP-13 inhibitor, WAY170523, or vehicle. To evaluate the effect of WAY170523, we used qRT-PCR to measure changes in the expression of fibrotic markers, COL1a1, COL3a1, and TGF-β. Inhibition of MMP-13 with WAY170523 attenuated expression of these genes compared to vehicle treated animals. We previously reported that stimulation of CF and cardiomyocytes with MMP-13 induces phosphorylation of ERK1/2, a member of the MAPK family known to play a role in cardiac hypertrophy, and treatment with a direct PAR-1 antagonist decreased the activation of ERK1/2. We have found that ERK1/2 phosphorylation is directly attenuated following inhibition of MMP-13 with WAY170523. Overall, these data suggest a role for MMP-13 dependent PAR-1 activation in pathologic myofibroblast transition and a potential therapeutic role for MMP-13 inhibition, possibly through its inhibition of ERK1/2 phosphorylation. Treatment with WAY170523 also attenuates markers of fibrosis in vivo, indicating a potential salutary role for MMP-13 inhibition in the treatment of HF.

Chromium oxide nanoparticle–induced biochemical and histopathological alterations in the kidneys and brain of Wistar rats

2017 ◽  
Vol 33 (12) ◽  
pp. 911-921 ◽  
Author(s):  
Ravish Fatima ◽  
Kafil Akhtar ◽  
M Mobarak Hossain ◽  
Riaz Ahmad
Keyword(s):  
Chromium Oxide ◽  
Wistar Rats ◽  
Ros Generation ◽  
High Dose ◽  
Once Daily ◽  
Group Type ◽  
Histopathological Alterations ◽  
Wide Range ◽  
Male Wistar Rats ◽  
Chromium Oxide Nanoparticles

Chromium oxide nanoparticles (Cr2O3 NPs) have a wide range of applications in industry. They are used as pigments, catalysts, wear-resistant or high-temperature-resistant coating material and are used in liquid crystal displays. In view of ever escalating use of NPs, risk assessment becomes obligatory to ensure the safety of both human health and the ecosystem. The present study was designed and conducted to evaluate biochemical changes and histopathological alterations in kidneys and brain of rats, following exposure to Cr2O3 NPs. Male Wistar rats were divided into low-dose (50 µg/100 g body weight (bwt) groups and high-dose (200 µg/100 g bwt) groups. Each group type received oral administration of Cr2O3 NPs for multiple durations (single dosing, once daily for 7 days and once daily for 14 days, respectively). According to our data, this allotment presented a meaningful picture of NPs behaviour in different scenarios. In the kidneys and brain of Cr2O3 NPs-exposed animals, reactive oxygen species (ROS) production caused a significant increase in malondialdehyde (MDA) concentration along with a significant decrease in superoxide dismutase and glutathione levels, as compared to controls. Histopathological changes in these organs confirmed cellular injury and functional damage due to exposure to Cr2O3 NPs. In this study, we have distinguished pathological alterations consequent to deleterious oxidative stress due to enhanced ROS generation after Cr2O3 NPs exposure.

scholarly journals Effect of a heme oxygenase-1 inducer on NADPH oxidase expression in alcohol-induced liver injury in male Wistar rats

2017 ◽  
Vol 16 (5) ◽  
pp. 1039 ◽  
Author(s):  
Phanit Koomhin ◽  
Chuchard Punsawad ◽  
Prasit Suwannalert ◽  
Sarawoot Palipoch
Keyword(s):  
Liver Injury ◽  
Nadph Oxidase ◽  
Heme Oxygenase ◽  
Wistar Rats ◽  
Heme Oxygenase 1 ◽  
Male Wistar Rats
Sign in / Sign up

Export Citation Format

Share Document