Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There is epidemiologic evidence that the prognosis of patients with nonischemic heart failure is better than that for patients with ischemic heart failure. In addition, studies have revealed that patients with ischemic heart failure show a poorer response to medical therapy. However, the pathophysiologic difference between ischemic and nonischemic heart disease is unclear. To clarify this point, we measured atrial natriuretic peptide, brain natriuretic peptide, angiotensin II, endothelin (ET)-1. interleukin-1beta interleukin-6. tumor necrosis factor (TNF)-alpha soluble TNF receptor I, and soluble TNF receptor II concentrations in plasma and pericardial fluid in patients with ischemic or nonischemic heart disease undergoing cardiac surgery. The pericardial ET-1 concentration in patients with ischemic heart disease was statistically greater than that in patients with nonischemic heart disease (about 1.5-fold), although no difference was found in the plasma ET-1 concentration. These findings suggest that the production and secretion of ET-1 from the myocardium in patients with ischemic heart disease are augmented to a greater extent than in patients with nonischemic heart disease. This result may lead to a greater understanding of the pathophysiology of ischemic heart disease.
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PMID:Endothelin-1 concentrations in pericardial fluid are more elevated in patients with ischemic heart disease than in patients with nonischemic heart disease. 1458 45

Mulibrey nanism is an autosomal recessive prenatal-onset growth disorder of unknown pathogenesis. The main clinical features are pre- and postnatal growth failure, characteristic dysmorphic craniofacial features, heart disease, and hepatomegaly. Five truncating mutations in the TRIM37 gene have previously been reported in Mulibrey nanism patients. The TRIM37 protein encodes a novel protein of unknown function. It contains a tripartite motif (TRIM, also denoted the RING-B-box-Coiled-coil or RBCC domain) and a TRAF (tumor necrosis factor-receptor associated factor) domain. TRIM37 localizes to peroxisomes classifying Mulibrey nanism as a peroxisomal disorder. Here we have characterized the genomic structure of the TRIM37 gene, which has 24 exons spanning approximately 109 kb of genomic DNA. Further, we report six novel disease-associated mutations, five of which predict a truncated protein: c.745C>T (p.Gln249X), c.1411C>T (p.Arg471X), c.2056C>T (p.Arg686X), and an 8.6 kb genomic deletion (c.1314+507_1668-207del resulting in p.Arg439fsX4). The sixth mutation (c.965G>T) is the first missense mutation (p.Gly322Val) associated with Mulibrey nanism. It affects the TRAF domain of TRIM37 and results in altered subcellular localization of the mutant TRIM37 protein, further suggesting that it is pathogenic.
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PMID:Novel mutations in the TRIM37 gene in Mulibrey Nanism. 1510 85

The Women Health Initiative Clinical trial results suggest that post-menopausal women receiving estrogen + progesterone are at risk for heart disease compared with estrogen alone supplemented women. We examined the hypothesis that progesterone but not 17beta-estradiol (E) increases the secretion of pro-inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha. U937 human monocytes were cultured with normal or high glucose in the presence and absence of estrogen or progesterone at 37 degrees C for 24 h. Results show that estrogen inhibits IL-6 but not TNF-alpha secretion (p < 0.05) in monocytes activated by lipopolysaccharide (LPS) or high glucose. In addition, progesterone increased the TNF-alpha secretion in activated monocytes. Thus, progesterone supplementation along with estrogen may increase blood levels of pro-inflammatory cytokine TNF-alpha and thus risk of heart disease in post-menopausal women.
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PMID:Progesterone, but not 17beta-estradiol, increases TNF-alpha secretion in U937 monocytes. 1513 3

In the developed world, Kawasaki disease is currently the leading cause of pediatric acquired heart disease. To date, the etiologic agent remains unknown. Many hypotheses regarding the etiology exist, and debate continues as to whether the inflammatory response of Kawasaki disease results from a superantigen or a conventional antigen. A variety of growth factors, proteinases, and cytokines have been identified that are involved in the pathogenesis of coronary artery disease in Kawasaki disease. These findings are leading to novel treatment strategies in Kawasaki disease, including platelet glycoprotein receptor inhibitors and monoclonal antibody to tumor necrosis factor-alpha. The role of corticosteroids remains controversial, and ongoing clinical trials are evaluating its efficacy. Additional studies have focused on newer non-invasive methods of evaluating children with coronary artery disease as alternatives to coronary catheterization. We review recent developments and controversies in exploring the etiology, pathogenesis, diagnosis, and management of Kawasaki disease.
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PMID:Recent developments and controversies in Kawasaki disease. 1524 14

A bidirectional relationship exists between depression and cardiovascular disease. Patients with major depression are more likely to develop cardiac events, and patients with myocardial infarction and heart failure are more likely to develop depression. A feature common to both clinical syndromes is activation of proinflammatory cytokines and stress hormones, including the hypothalamic-pituitary-adrenal axis and the renin-angiotensin-aldosterone system. In the present study we examined the hypothesis that exposure to chronic mild stress (CMS), an experimental model of depression that induces anhedonia in rats, is sufficient to activate the production of proinflammatory cytokines and stress hormones that are detrimental to the heart and vascular system. Four weeks of exposure of male, Sprague-Dawley rats to mild unpredictable environmental stressors resulted in anhedonia which was operationally defined as a reduction in sucrose intake without a concomitant effect on water intake. Humoral assays indicated increased plasma levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), plasma renin activity, aldosterone, and corticosterone in the CMS exposed rats. Tissue TNF-alpha and IL-1beta were increased in the hypothalamus, and TNF-alpha was increased in the pituitary gland. These humoral responses to CMS, associated with anhedonia as an index of depression in the rat, are likely to be associated with neurohumoral mechanisms that may contribute to adverse cardiac events. The findings provide a basis for examining more directly the interactions among the central, endocrine, and immune systems in depression associated with heart disease.
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PMID:Neuroendocrine and cytokine profile of chronic mild stress-induced anhedonia. 1588 45

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

Consumption of fruits and vegetables is associated with a reduced risk of death from all causes including heart disease and stroke. In this work, the bioavailability of vitamin C from a Mediterranean vegetable soup (gazpacho) constituted mainly of tomato, pepper and cucumber, and its influence on plasma vitamin C, 8-epi-prostaglandin F(2alpha) (8-epi-PGF2alpha), prostaglandin E2 (PGE2), monocyte chemotactic protein-1 (MCP-1), and the cytokines/tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and IL-6 concentrations in a healthy human population were assessed. Six men and six women consumed 500 ml of commercial gazpacho per day for 14 days, corresponding to an intake of 78 mg of ascorbic acid per day. There were no differences (P = .22) in baseline plasma vitamin C concentrations between the men and women. The maximum increase (P < .05) in plasma vitamin C occurred 4 h postdose in both men and women. Vitamin C concentrations were significantly higher (P < .03) on Days 7 and 14 of the intervention. Baseline concentrations of uric acid and 8-epi-PGF2alpha were significantly higher (P < or = .032) in men than in women. Baseline concentrations of 8-epi-PGF2alpha decreased significantly (P < or = .05) by Day 14 of the intervention. A significant inverse correlation was observed between vitamin C and 8-epi-PGF2alpha (r = -.415, P = .049). Baseline concentrations of PGF2 and MCP-1 were significantly higher (P< or = .025) in men than in women but decreased significantly (P< or = .05) by Day 14 of the intervention. No effect on TNF-alpha, IL-1beta and IL-6 was observed at Day 14 of the intervention. Drinking gazpacho (500 ml/day) significantly increases plasma concentrations of vitamin C and significantly decreases 8-epi-PGF2alpha, PGE2 and MCP-1 concentrations in healthy humans.
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PMID:Mediterranean vegetable soup consumption increases plasma vitamin C and decreases F2-isoprostanes, prostaglandin E2 and monocyte chemotactic protein-1 in healthy humans. 1616 5

Matrix metalloproteinases (MMPs) are members of an enzyme family that require a zinc ion in their active site for catalytic activity. MMPs are critical for maintaining tissue allostasis. MMPs are active at neutral pH and can therefore catalyze the normal turnover of extracellular matrix (ECM) macromolecules such as the interstitial and basement membrane collagens, proteoglycans such as aggrecan, decorin, biglycan, fibromodulin and versican as well as accessory ECM proteins such as fibronectin. Members of the MMP family include the "classical" MMPs, the membrane-bound MMPs (MT-MMPs) the ADAMs (a disintegrin and metalloproteinase; adamlysins) and the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motif). There are more than 20 members in the MMP and ADAMTS family including the collagenases, gelatinases, stromelysins, some elastases and aggrecanases. Adamlysins are membrane-bound MMPs that also degrade aggrecan, but more importantly, one ADAM family member (i.e.ADAM-17) is a tumor necrosis factor-alpha (TNF-alpha)-converting enzyme (TACE) that activates pro-TNF-alpha. Most of the MMPs are synthesized as inactive latent enzymes. Conversion to the active enzyme is generally mediated by activator systems that include plasminogen activator or the pro-hormone convertase, furin. MMP activity is regulated by a group of endogenous proteins, called, tissue inhibitor of metalloproteinases (TIMPs) that bind to active and alternative sites of the activated MMP. Significant advances have occurred in the understanding of the regulation of MMPs, ADAMs and ADAMTSs gene expression. In addition, development of MMP inhibitors to study MMP structure/function relationships spawned many studies to determine the effectiveness of MMP inhibitors in regulating abnormal connective tissue turnover. In addition, development of MMP null mice carrying specific MMP deletions has provided an opportunity to explore the role of MMPs in normal development as well as in such diverse conditions and diseases as skeletal dysplasias, coronary artery and heart disease, arthritis, cancer, and brain disorders.
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PMID:Matrix metalloproteinases (MMPs) in health and disease: an overview. 1636 48

Surgical treatment of complex congenital heart disease under extracorporeal circulation is accompanied by a systemic inflammatory reaction occurring in neonatal infants and babies. There were drastic increases in the concentration of tumor necrosis factor, interleukin-8, neutrophilic elastase and a predominance of a proinflammatory response over an inflammatory one at the warming stages and after administration of protamine sulfate. The rate of an inflammatory response depended on the duration of extracorporeal circulation. Modified ultrafiltration could remove cytokines; however, their concentration in the body remains high. A relationship was found between the course of a postoperative period and the rate of a developing reaction to extracorporeal circulation in the surgical treatment of congenital heart diseases.
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PMID:[Inflammatory response mediators in newborns and infants with congenital heart diseases during surgical treatment under extracorporeal circulation]. 1688 10

Heart disease and depression are highly co-morbid. Clinical and experimental research over the past 70 years has led to several neurohumoral hypotheses of causative factors present under the conditions of either heart failure or of psychological depression. Some of these hypothesized factors are common to both disorders and are therefore attractive candidates to account for the high incidence of co-occurrence of depression and heart disease. One experimental approach to study the co-morbidity of heart failure and depression has been to study the behavioral, biochemical and physiological changes in a chronic mild stress model of depression and in heart failure induced by experimental myocardial infarction. Our studies have led us to focus on the pro-inflammatory cytokines, in particular tumor necrosis factor (TNF)-alpha, and the renin-angiotensin-aldosterone system. Both of these families of humoral factors are elevated in human heart failure and in depression and the two experimental models we have studied. The demonstrated validity of each of these models will be of great value in elucidating the nature of the actions and interactions of these humoral agents as they contribute to the co-morbid conditions of heart failure and depression.
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PMID:Sadness and broken hearts: neurohumoral mechanisms and co-morbidity of ischemic heart disease and psychological depression. 1724 36


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