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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Four classes of agents capable of producing human illness have been identified: toxicity, heredity, infection and deficiency. The leading paradigm for the etiology and pathophysiology of ischemic heart disease in the 20th century was that of intoxication by too much of the wrong kind of dietary fat. This overemphasis on lipid metabolism persists because important data are neglected and because of inattention to details. For example, heart disease risk does not correlate with fat intake within nations in contrast to between nations. Also development of ischemic heart disease involves inter alia arterial spasm, cardiac rhythm, metabolism of connective tissue, glucose and homocysteine, plus paraoxonase activity and thrombus formation which generally are unaffected by dietary fat. Homocysteine thiolactone accumulates when homocysteine is high. This lactone specifically inhibits lysyl oxidase which depends on copper to catalyze cross linking of collagen and elastin in arteries and bone. The lactone is hydrolyzed by paraoxonase, activity of which can be decreased by copper deficiency. Just as cholesterol was an important focus for heart disease as intoxication, homocysteine can become an excellent focus for a paradigm shift to heart disease as deficiency because supplementation with several nutrients can alter homocysteine metabolism and decrease its plasma concentration. These supplements include betaine, copper, folate, pyridoxine and vitamin B-12. Opportunities for research on ischemic heart disease as deficiency disease are plentiful.
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PMID:Ischemic heart disease as deficiency disease. 1570 51

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

Ischemic stroke is a complex entity with multiple etiologies and variable clinical manifestations. The most frequent cause of stroke is atherosclerosis of cerebral vasculature followed by cardioembolism. Two thirds of strokes are explained by identifiable risk factors. Age, hypertension, and nonvalvular atrial fibrillation are by far the most frequent and well documented ones. Approximately 5% of strokes are caused by conditions other than atherosclerosis or heart disease, i.e., cervical arteries dissections, nonatherosclerotic vasculopathies, infectious or systemic vasculitis, and collagen vascular diseases. In spite of a thorough diagnostic evaluation, 30% of strokes remain cryptogenic, i.e., no specific cause is identified and the classic risk factors are not present. Identification of unknown environmental or genetic risk factors should be the subject of further research.
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PMID:What proportion of stroke is not explained by classic risk factors? 1572 93

We report heterozygous mutations in the genes encoding either type I or type II transforming growth factor beta receptor in ten families with a newly described human phenotype that includes widespread perturbations in cardiovascular, craniofacial, neurocognitive and skeletal development. Despite evidence that receptors derived from selected mutated alleles cannot support TGFbeta signal propagation, cells derived from individuals heterozygous with respect to these mutations did not show altered kinetics of the acute phase response to administered ligand. Furthermore, tissues derived from affected individuals showed increased expression of both collagen and connective tissue growth factor, as well as nuclear enrichment of phosphorylated Smad2, indicative of increased TGFbeta signaling. These data definitively implicate perturbation of TGFbeta signaling in many common human phenotypes, including craniosynostosis, cleft palate, arterial aneurysms, congenital heart disease and mental retardation, and suggest that comprehensive mechanistic insight will require consideration of both primary and compensatory events.
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PMID:A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or TGFBR2. 1573 57

Radiation-induced heart disease (RIHD), characterized by accelerated atherosclerosis and adverse tissue remodeling, is a serious sequelae after radiotherapy of thoracic and chest wall tumors. Adverse cardiac remodeling in RIHD and other cardiac disorders is frequently accompanied by mast cell hyperplasia, suggesting that mast cells may affect the development of cardiac fibrosis. This study used a mast cell-deficient rat model to define the role of mast cells in RIHD. Mast cell-deficient rats (Ws/Ws) and mast cell-competent littermate controls (+/+) were exposed to 18 Gy localized single-dose irradiation of the heart. Six months after irradiation, cardiac function was examined by echocardiography and Langendorff-perfused isolated heart preparation, whereas structural changes were assessed using quantitative histology and immunohistochemical analysis. Mast cell-deficient rats exhibited more severe postradiation changes than mast cell-competent littermates. Hence, mast cell-deficient rats exhibited a greater upward/leftward shift in the left ventricular (LV) diastolic pressure-volume relationship (P = 0.001), a greater reduction in in vivo LV diastolic area (from 0.50 +/- 0.024 cm in age-matched controls to 0.24 +/- 0.032 cm after irradiation; P = 0.006), and a greater increase in LV posterior wall thickness (from 0.13 +/- 0.003 cm in age-matched controls to 0.15 +/- 0.003 cm after irradiation; P = 0.04). Structural analysis revealed more pronounced postradiation accumulation of interstitial collagen III but less myocardial degeneration in hearts from mast cell-deficient rats. These data show that the absence of mast cells accelerates the development of functional changes in the irradiated heart, particularly diastolic dysfunction, and suggest that, in contrast to what has been the prevailing assumption, the role of mast cells in RIHD is predominantly protective.
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PMID:Influence of mast cells on structural and functional manifestations of radiation-induced heart disease. 1583 39

We report here a patient with features of Down syndrome and tetralogy of Fallot who had a 21q22 duplication. The extent of the duplication was defined using fluorescent hybridization probes that map to the critical region on chromosome 21. Included within the interval was the cell adhesion molecule DSCAM but not the collagen COL6A1. The present case provides further support to the concept that there exists Down syndrome-associated congenital heart disease gene(s) on chromosome 21q22 and that over-expression of DSCAM may contribute to the cardiac defects of Down syndrome.
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PMID:Refining chromosomal region critical for Down syndrome-related heart defects with a case of cryptic 21q22.2 duplication. 1590 34

Coronary artery disease is the number one cause of death in the United States and the Western world, and approximately 250,000 affected people die per year without ever being admitted to a hospital. One of the main reasons of such a high death-rate without any diagnosis is that more than 50 or heart-attacks) occur in patients with no prior history of known heart disease or symptoms. Coronary artery disease leads to the occlusion of arteries that are vital in providing nutrients to the heart muscles. The disease develops by progressive accumulation or formation of "plaque" within an artery. Certain types of plaques could occlude blood flow and yet might be "stable". These plaques usually have a high fibrous content, and are known as hard plaques. On the other hand, "unstable" or "soft" plaques might not cause much occlusion but could be vulnerable to rupture. Rupture of such plaques could lead to total or partial occlusion in arteries resulting in sudden cardiac death or heart-attack. In fact, 68 coronary arteries are less than 50.Intravascular ultrasound (IVUS) is a minimally invasive imaging modality that provides cross-section images of arteries in real-time, allowing visualization of atherosclerotic plaques in vivo. In standard IVUS gray-scale images, calcified regions of plaque and dense fibrous components generally reflect ultrasound energy well and thus appear bright and homogeneous on IVUS images. Conversely, regions of low echo reflectance in IVUS images are usually labeled "soft" or "mixed" plaque. However, this visual interpretation has been demonstrated to be very inconsistent in accurately determining plaque composition and does not allow real-time assessment of quantitative plaque constituents.Spectral analysis of the backscattered radiofrequency (RF) ultrasound signals allows detailed assessment of plaque composition. Advanced mathematical techniques can be employed to extract spectral information from these RF data to determine composition. The spectral content or signature of RF data reflected from tissue depends on density, compressibility, concentration, size, etc. A combination of spectral parameters were used to develop statistical classification schemes for analysis of in vivo IVUS data in real-time. The clinical data acquisition system is ECG gated and the analysis software developed by our group reconstructs IVUS gray-scale images from the acquired RF data. A combination of spectral parameters and active contour models is used for real-time 3D plaque segmentation followed by computation of color-coded tissue maps for each image cross-section and longitudinal views of the entire vessel. The "fly-through" mode allows one to visualize the complete length of the artery internally with the histology components at the lumen surface. In addition, vessel and plaque metrics such as areas and volumes of individual plaque components (collagen, fibro-lipid, calcium, lipid-core) are also available.
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PMID:Real-time plaque characterization and visualization with spectral analysis of intravascular ultrasound data. 1592 46

Cardiac fibrosis is a hallmark of heart disease and involves recruitment, proliferation, and differentiation of extracellular matrix-producing fibroblasts, leading to overproduction of collagen within the myocardium. In this study, the effects of relaxin in inhibiting these processes were investigated. We used neonatal rat atrial and ventricular fibroblasts, which respond to pro-fibrotic stimuli (i.e., transforming growth factor-beta and angiotensin II) and naturally express the relaxin receptor LGR7. Relaxin significantly inhibited TGF-beta- and angiotensin II-mediated fibroblast function and collagen production over a 72-h period, while increasing MMP-2 expression and activity in the presence of both profibrotic factors (all P < .05). These studies demonstrate that relaxin may have therapeutic potential in diseased states characterized by cardiac fibrosis.
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PMID:Relaxin modulates fibroblast function, collagen production, and matrix metalloproteinase-2 expression by cardiac fibroblasts. 1595 6

Cerebral mycotic aneurysms are one of the most serious complications of bacterial endocarditis but the mechanism underlying cerebral aneurysms is unclear. We reported the cytokine levels in a cerebral mycotic aneurysm in a child with Down's syndrome. The patient was a 12-year-old female. She was diagnosed as having Down's syndrome and congenital heart disease consisting of an endocardial cushion defect at birth. She underwent a radical operation at 9 years but mitral valve regurgitation remained. She was hospitalized with high fever, vomiting, loss of activity and gait disturbance. Neurological examination revealed facial palsy and hemiparesis on the left side. Cytokines such as IL-6, TNF-alpha, sTNFR1 and sE-selectin were elevated in blood, and IL-6, TNF-alpha and sTNFR1 in cerebrospinal fluid. T2-weighted MRI disclosed a low intensity area in the right Sylvian sulcus. MR angiography showed an aneurysm of the right middle cerebral artery. We think that cytokines and the formation abnormality of collagen fibers are related to the production of aneurysms.
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PMID:Increased cytokine levels in a cerebral mycotic aneurysm in a child with Down's syndrome. 1612 32

Type XVIII collagen is a multidomain protein that contains cleavable C-terminal NC1 and endostatin fragments, which have been shown to either induce or inhibit cell migration. Endostatin is being intensely studied because of its anti-angiogenic activity. Three variants of type XVIII collagen have been reported to be distributed in epithelial and endothelial basement membranes in a tissue-specific manner. The single gene encoding collagen XVIII is on chromosome 21 within the region associated with the congenital heart disease phenotype observed in Down's syndrome. In this study, we investigated the expression pattern of collagen XVIII in embryonic mouse hearts during formation of the atrioventricular (AV) valves. We found that collagen XVIII is localized not only in various basement membranes but is also highly expressed throughout the connective tissue core of the endocardial cushions and forming AV valve leaflets. It was closely associated with the epithelial-mesenchymal transformation of endothelial cells into mesenchymal cushion tissue cells and was localized around these cells as they migrated into the cardiac jelly to form the initial connective tissue elements of the valve leaflets. However, after embryonic day 17.5 collagen XVIII expression decreased rapidly in the connective tissue and thereafter remained detectable only in the basement membranes of the endothelial layer covering the leaflets. The staining pattern observed within the AV endocardial cushions suggests that collagen XVIII may have a role in cardiac valve morphogenesis. These results may help us to better understand normal heart development and the aberrant mechanisms that cause cardiac malformations in Down's syndrome.
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PMID:Collagen XVIII/endostatin is associated with the epithelial-mesenchymal transformation in the atrioventricular valves during cardiac development. 1617 Jul 84


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