UMLS:C0018801 - FACTA Search

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Query: UMLS:C0018801 (heart failure)
72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present study focuses on lesions of the pericardium commonly observed in fast growing broilers. These lesions are examined in the context of electrophysiological and functional changes associated with cardiac performance and patho-physiology in broilers succumbing to acute or chronic heart failure. Typical lesions involving the pericardium in fast growing broiler chickens included: (1) excessive pericardial effusion, (2) locally extensive or focal adhesions between parietal and visceral components of the pericardium, (3) fibrous deposits on visceral pericardium, and (4) thickened pericardium. Echocardiographic evidence indicated that severe pericardial effusion and/or adhesions may have a restrictive effect on heart pump function, where both diastolic and systolic function of the heart may be affected. Electrocardiographic data showed a strong trend indicating that pericardial adhesions may be associated with ventricular arrhythmia and increased risk of sudden death in fast growing broilers. Relatively high levels of matrix metalloproteinase MMP-2 activity have been found in pericardial effusions from affected chickens, suggesting a possible involvement of this enzyme in the aetiology of pericardial lesions. The present results indicate that pericardial lesions may be associated with biochemical, morphological, electrophysiological, and functional changes occurring in the hearts of broilers succumbing to acute or chronic heart failure and ascites.
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PMID:Lesions of the pericardium and their significance in the aetiology of heart failure in broiler chickens. 1272 38

Remodelling of extracellular matrix by activated matrix metalloproteinases is considered to contribute to progression of ventricle remodelling during chronic heart failure. The aim of this study was to associate two promoter polymorphisms, -790T/G and -735C/T, in the gene for matrix metalloproteinase (MMP)-2 (gelatinase A) with chronic heart failure (CHF). For this purpose, 164 patients (124 men, 40 women, median age 56 years, range 21-91 years) with CHF (functional class NYHA II-IV, ejection fraction median 25%, cardiothoracic index more than 50%) were compared with 196 control subjects without clinical signs of cardiovascular disease (131 men and 65 women, median age 56 years, range 27-84 years) in -790T/G and -735C/T MMP-2 genotype distributions and allelic frequencies. The genotypes were determined by polymerase chain reaction (PCR) with restriction analyses. A significant increase of the T allele of the -790T/G MMP-2 polymorphism (p = 0.04), as well as of the C allele of the -735C/T MMP-2 gene polymorphism, in patients with CHF was proven (p = 0.04). The heterozygote CT of the -735C/T MMP-2 polymorphism exhibits a 7 times higher odds ratio (OR) for the CHF patients with lower levels of total cholesterol (less than 5 mmol/l), especially for non-hypertensive CHF men (OR = 7.28, 95% confidence interval 1.51-35.03, p = 0.006). Determination of MMP polymorphisms in the regulatory area of the gene could help us to comprehend individual susceptibility of patients with CHF to MMP inhibitors based on known risks of MMP genotypes.
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PMID:Two MMP-2 promoter polymorphisms (-790T/G and -735C/T) in chronic heart failure. 1458 Jan 55

The precise correlation between magnesium and cardiac disease remains to be established. Matrix metalloproteinases (MMPs) are important in cardiac disease such as heart failure. Cardiac fibroblasts are the most abundant cell type in the heart and play an important role in the regulation of collagen degradation by MMPs. To assess the association between magnesium and MMPs, we examined the effects of different extracellular magnesium concentrations (0-3.0 mmol/L) on MMP-2 production in cultured rat cardiac fibroblasts. Using gelatin zymography and western blotting, we found that magnesium reduced MMP-2 production dose-dependently, and this effect was inhibited by the tyrosine kinase inhibitors, genistein or herbimycin A. The results of this study indicated that the beneficial effect of magnesium supplementation on the cardiac disease may be due, at least in part, to the inhibitory effect of magnesium on production of MMPs in cardiac fibroblasts, which appears to be mediated by a protein tyrosine phosphorylation related signal transduction pathway.
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PMID:Effects of magnesium on matrix metalloproteinase-2 production in cultured rat cardiac fibroblasts. 1522 43

Dietary copper (Cu) restriction leads to cardiac hypertrophy and failure in mice, and Cu repletion (CuR) reverses the hypertrophy and prevents the transition to heart failure. The present study was undertaken to determine changes in myocardial gene expression involved in Cu deficient (CuD) cardiomyopathy and its reversal by CuR. Analysis was performed on three groups of mice: 4-week-old CuD mice that exhibited signs of cardiac failure, their age-matched copper-adequate (CuA) controls, and the CuD mice that were re-fed adequate Cu for 2 weeks. Total RNA was isolated from hearts and subjected to cDNA micro-array and real-time reverse transcription-polymerase chain reaction analysis. Dietary CuD caused a decrease in cardiac mRNA of beta-MHC, L-type Ca(2+) channel, K-dependent NCX, MMP-2, -8, and -13, NF-kappaB, and VEGF. The mRNA levels of ET-1, TGF-beta, TNF-alpha, and procollagen-I-alpha1 and III-alpha1 were increased in the CuD cardiac tissue. Copper repletion resulted in cardiac mRNA levels of most of the genes examined returning to control levels, although the K-dependent NCX and MMP-2 values did not reach those of the CuA control. In addition, CuR caused an increase in beta-MHC, L-type Ca(2+)channel, MMP-13 to levels surpassing those of CuA control, and a decrease in ET-1, and TNF-alpha mRNA levels. In summary, changes in gene expression of elements involved in contractility, Ca(2+) cycling, and inflammation and fibrosis may account for the altered cardiac function found in CuD mice. The return to normal cardiac function by CuR may be a result of the favorable regression in gene expression of these critical components in myocardial tissue.
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PMID:Dietary copper restriction-induced changes in myocardial gene expression and the effect of copper repletion. 1522 55

Left ventricular (LV) remodeling following myocardial infarction (MI) is a complex process involving extracellular matrix degradation and fibrosis. While early remodeling is beneficial, chronic remodeling leads to decompensated heart failure (HF). We assessed the hypothesis that activation of the plasminogen-MMP system is involved in the remodeling of the infarct scar and compared it to the remaining viable myocardium. MI was induced by coronary artery ligature in 42 male Wistar rats. Three months following surgery, animals were divided into compensated (n=26) or decompensated (n=16) groups and compared to sham-operated rats (n=17). Scar and remaining viable LV myocardium (LVM) were separately analyzed for MMP-2, -7, -9, urokinase type and tissue type plasminogen activator (uPA and tPA) mRNA levels by RT-PCR. Their protein or activity levels, plus those of plasminogen/plasmin, tissue inhibitor of metalloproteinase-1, -2, -4 (TIMP-1, -2, -4) and plasminogen activator inhibitor-1 (PAI-1) were analyzed in tissue conditioned media by Western blot, ELISA and/or zymography. MMP and plasmin proteolytic activities were increased in the scar as compared to paired LVM thus indicating that activation of plasminogen and pro-MMPs is a key event in scar tissue remodeling. MMP and plasminogen activators (uPA, tPA) mRNAs were increased accordingly. Furthermore, inhibitors of the proteolytic enzymes, TIMP-1 and PAI-1 were increased in the scars from failing hearts and LVM thus suggesting a dynamic interplay between proteolysis and its inhibitors. This study shows a high degree of activation of the MMP-plasminogen system and the balance with their inhibitors in the infarcted myocardium, and suggests that this activation participates more to the remodeling of the scar tissue than to the remaining myocardium.
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PMID:The plasminogen-MMP system is more activated in the scar than in viable myocardium 3 months post-MI in the rat. 1562 36

We examined the hypothesis that oxidants generated nitroso derivatives, activated latent matrix metalloproteinase (MMP), and induced proteinase-activated receptor 1 (PAR-1), leading to disconnection between the endothelium and myocytes. Administration of cardiospecific tissue inhibitor of metalloproteinase-4 (TIMP-4/CIMP) ameliorated the oxidative-proteolytic stress and endothelial-myocyte uncoupling in chronic heart failure (CHF) in mice. Aortic-vena cava fistula (AVF) was created in 30 male mice (C57BL/6J) and studied at 0-, 2-, and 8-wk AVF. To reverse cardiac remodeling, as measured by MMP activation, purified CIMP was administered by an osmotic minipump subcutaneously after 8-wk AVF, and groups of mice (n = 6 mice/group) were examined after 12 and 16 wk. Levels of PAR-1 in the left ventricle (LV) were increased at 2 and 8 wk (compared with 0 wk of no CIMP treatment) but were normal at 12 and 16 wk after CIMP treatment, as measured by Western blot analysis. Similar results were obtained for LV levels of nitrotyrosine, MMP-2 and -9 activities, and TIMP-1 and -3. However, the levels of TIMP-4, endothelial cell density, and responses of cardiac rings to acetylcholine and bradykinin were attenuated at 2 and 8 wk and normalized after CIMP administration in AVF mice. CIMP induced nitric oxide in microvascular endocardial endothelial cells. The results suggest that nitro generation activated MMP and PAR-1, leading to endothelial-myocyte uncoupling. CIMP treatment normalized PAR-1 expression and ameliorated endothelial-myocyte uncoupling by decreasing oxidant-mediated proteolytic stress in CHF.
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PMID:Protease-activated receptor and endothelial-myocyte uncoupling in chronic heart failure. 1568 8

There are fundamental differences between males and females with regard to susceptibility to heart disease. Although numerous animal models of heart failure have demonstrated that premenopausal females are afforded cardioprotection and, therefore, fare better in the face of cardiac disease than their male counterparts, many questions as to how this occurs still exist. Recently, we showed that 1) increased mast cell density is associated with adverse ventricular remodeling and 2) chemically induced mast cell degranulation using compound 48/80 resulted in remarkable changes in matrix metalloproteinase (MMP) activity, cardiac collagen structure, and cardiac diastolic function in normal male rats. With the known gender differences in cardiac disease in mind, we sought to examine the effects of chemically induced cardiac mast cell degranulation in isolated, blood-perfused hearts of intact female rats, ovariectomized female rats, and ovariectomized female rats treated with 17beta-estradiol. In response to mast cell degranulation, no significant differences in cardiac function, MMP-2 activity, or collagen volume fraction were observed between intact female rats and ovariectomized female rats treated with estrogen. In the ovariectomized female group, a significant rightward shift in the left ventricular pressure-volume relation, accompanied by a marked 133% increase in active MMP-2 values over that in the intact female group, was noted after treatment with compound 48/80 (P < or = 0.05), along with a significant reduction in collagen volume fraction below control (0.46 +/- 0.23 vs. 0.73 +/- 0.13%, P < or = 0.05). These findings indicate that estrogen's cardioprotective role can be partially mediated by its effects on cardiac mast cells, MMPs, and the extracellular matrix.
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PMID:Modulation of cardiac mast cell-mediated extracellular matrix degradation by estrogen. 1572 8

Tumor embolism occurs in 30 to 50% of all cases of cardiac myxoma, but the causes are still uncertain. Matrix metalloproteinases (MMPs) are proteolytic enzymes that degrade the extracellular matrix (ECM) and play a crucial role in plaque instability and aortic aneurysm development, in addition to cancer and heart failure. To determine whether MMP activity contributes to tumor embolism, we examined 27 left atrium-sided myxomas, 10 of which showed clinical signs of peripheral embolism. Immunohistochemistry (in all cases) and Western blotting, and in situ and in-gel zymography (in four embolic and six nonembolic consecutive tumors) demonstrated higher expression and activity of MT1-MMP, pro-MMP-2, and pro-MMP-9 in embolic myxomas, whereas pro-MMP-1, MMP-3, and TIMP-1 levels were similar to those of nonembolic tumors. Reverse transcriptase-polymerase chain reaction demonstrated that increased MMP activity was due, at least in part, to increased transcription and that TIMP-2 transcripts increased in embolic myxomas. In vitro, embolic tumor cells retained higher MT1-MMP and pro-MMP-2 levels in basal conditions and after stimulation with interleukin-1beta and interleukin-6. Increased MMP synthesis and release correlated with enhanced ECM degradation products containing glycosaminoglycan chains in embolic myxoma tissue. Our results strongly suggest that MMP overexpression may contribute to an excessive degradation of tumor ECM and increase the risk of embolism in cardiac myxomas.
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PMID:Increased expression and activity of matrix metalloproteinases characterize embolic cardiac myxomas. 1592 Jan 47

Tumor necrosis factor-alpha (TNF-alpha) plays a pathophysiological role in the development and progression of heart failure. Matrix metalloproteinase (MMP)-2 is involved in extracellular matrix remodeling. Recent evidence suggests a protective role for this protease against tissue inflammation. Although MMP-2 is upregulated in the failing heart, little is known about its pathophysiological role. We thus hypothesized that ablation of the MMP-2 gene could affect cardiac remodeling and failure in TNF-alpha-induced cardiomyopathy. We crossed transgenic mice with cardiac-specific overexpression of TNF-alpha (TG) with MMP-2 knockout (KO) mice. Four groups of male and female mice were studied: wild-type (WT) with wild MMP-2 (WT/MMP(+/+)), WT with MMP-2 KO (WT/MMP(-/-)), TNF-alpha TG with wild MMP-2 (TG/MMP(+/+)), and TG with MMP-2 KO (TG/MMP(-/-)). The upregulation of MMP-2 zymographic activity in TG/MMP(+/+) mice was completely abolished in TG/MMP(-/-) mice, and other MMPs and tissue inhibitors of metalloproteinase were comparable between groups. Survival was shorter for male TG/MMP(-/-) than TG/MMP(+/+) mice. Female TG/MMP(-/-) mice were more severely affected than TG/MMP(+/+) mice with diminished cardiac function. Myocardial TNF-alpha and other proinflammatory cytokines were increased in TG/MMP(+/+) mice, and this increase was similarly observed in TG/MMP(-/-) mice. The extent of myocardial infiltrating cells including macrophages was greater in TG/MMP(-/-) than in TG/MMP(+/+) mice. Selective ablation of the MMP-2 gene reduces survival and exacerbates cardiac failure in association with the increased level of myocardial inflammation. MMP-2 may play a cardioprotective role in the pathogenesis of cytokine-induced cardiomyopathy.
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PMID:Selective disruption of MMP-2 gene exacerbates myocardial inflammation and dysfunction in mice with cytokine-induced cardiomyopathy. 1593 97

Cytokine and extracellular matrix (ECM) homeostasis are distinct systems that are each dysregulated in heart failure. Here we show that tissue inhibitor of metalloproteinase (TIMP)-3 is a critical regulator of both systems in a mouse model of left ventricular (LV) dilation and dysfunction. Timp-3(-/-) mice develop precipitous LV dilation and dysfunction reminiscent of dilated cardiomyopathy (DCM), culminating in early onset of heart failure by 6 weeks, compared with wild-type aortic-banding (AB). Timp-3 deficiency resulted in increased TNFalpha converting enzyme (TACE) activity within 6 hours after AB leading to enhanced tumor necrosis factor-alpha (TNFalpha) processing. In addition, TNFalpha production increased in timp-3(-/-)-AB myocardium. A significant elevation in gelatinase and collagenase activities was observed 1 week after AB, with localized ECM degradation in timp-3(-/-)-AB myocardium. Timp-3(-/-)/tnfalpha(-/-) mice were generated and subjected to AB for comparative analyses with timp-3(-/-)-AB mice. This revealed the critical role of TNFalpha in the early phase of LV remodeling, de novo expression of Matrix metalloproteinases (MMP)-8 in the absence of TNFalpha, and highlighted the importance of interstitial collagenases (MMP-2, MMP-13, and MT1-MMP) for cardiac ECM degradation. Ablation of TNFalpha, or limiting MMP activity with a synthetic MMP inhibitor (PD166793), each partially attenuated LV dilation and cardiac dysfunction in timp-3(-/-)-AB mice. Notably, combining TNFalpha ablation with MMP inhibition completely rescued heart disease in timp-3(-/-)-AB mice. This study provides a basis for anti-TNFalpha and MMP inhibitor combination therapy in heart disease.
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PMID:Combination of tumor necrosis factor-alpha ablation and matrix metalloproteinase inhibition prevents heart failure after pressure overload in tissue inhibitor of metalloproteinase-3 knock-out mice. 1603 68

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