Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Calcification and ossification of soft tissues occurs as a response to a variety of injuries such as atherosclerosis, myositis ossificans, and caseous necrosis. These injuries and others have as a unifying characteristic persistent necrotic tissue elements. Normal tissues may calcify under conditions of hypercalcemia or hyperphosphatemia. The initial mobilization of Ca and P following injury is rapid, as observed in calcergy. The mitochondria of cells, normally a storehouse of Ca, become preferential sites of precipitated Ca when cells are irreversibly injured, and act as foci of progressive calcification. Collagen fibers undergo calcification directly, principally when they are located within devitalized sites such as prosthetic heart valves, and direct calcification of collagen may predominate generally in dystrophic calcification. VArious porous sponges act as foci for calcification and ossification, and the utilization of porous implants may provide for the development of therapeutically useful calcifying and ossifying biomaterials.
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PMID:Mineralization of connective tissue surrounding implanted devices. 733 Nov 58

Cardiovascular motality is high in patients with chronic renal failure treated with dialysis, and secondary hyperparathyroidism may promote atherosclerogenesis. Recent studies have revealed advanced atherosclerosis in hemodialysis patients by using high-resolution B-mode ultrasonography. Multiple regression analyses indicated that hyperphosphatemia and hyperparathyroidism were associated with increased intima-media thickness (IMT) of the carotid and femoral arteries in hemodialysis patients, respectively. Hypocalcemia and hyperparathyroidism independently and adversely affect the lipoprotein profile by suppressing hepatic triglyceride lipase (HTGL), a lipid-regulating enzyme playing important roles in the metabolism of intermediate density lipoprotein (IDL) and high density lipoprotein (HDL). Plasma IDL is raised markedly, and HDL is lowered in uremia. These lipoprotein changes are closely associated with increased aortic pulse wave velocity (PWV), an index of aortic sclerosis. These findings support the hypothesis that deranged calcium-phosphate homeostasis and secondary hyperparathyroidism promote atherosclerosis in uremia, at least partly by affecting lipoprotein metabolism. Adequate dialysis and efforts to normalize calcium, phosphate and PTH would be beneficial in preventing not only bone disease, but atherosclerosis as well.
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PMID:Atherosclerosis in uremia: possible roles of hyperparathyroidism and intermediate density lipoprotein accumulation. 935 Jun 91

Vascular calcification is a common finding in atherosclerosis and a serious problem in diabetic and uremic patients. Because of the correlation of hyperphosphatemia and vascular calcification, the ability of extracellular inorganic phosphate levels to regulate human aortic smooth muscle cell (HSMC) culture mineralization in vitro was examined. HSMCs cultured in media containing normal physiological levels of inorganic phosphate (1.4 mmol/L) did not mineralize. In contrast, HSMCs cultured in media containing phosphate levels comparable to those seen in hyperphosphatemic individuals (>1.4 mmol/L) showed dose-dependent increases in mineral deposition. Mechanistic studies revealed that elevated phosphate treatment of HSMCs also enhanced the expression of the osteoblastic differentiation markers osteocalcin and Cbfa-1. The effects of elevated phosphate on HSMCs were mediated by a sodium-dependent phosphate cotransporter (NPC), as indicated by the ability of the specific NPC inhibitor phosphonoformic acid, to dose dependently inhibit phosphate-induced calcium deposition as well as osteocalcin and Cbfa-1 gene expression. With the use of polymerase chain reaction and Northern blot analyses, the NPC in HSMCs was identified as Pit-1 (Glvr-1), a member of the novel type III NPCs. These data suggest that elevated phosphate may directly stimulate HSMCs to undergo phenotypic changes that predispose to calcification and offer a novel explanation of the phenomenon of vascular calcification under hyperphosphatemic conditions. The full text of this article is available at http://www.circresaha.org.
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PMID:Phosphate regulation of vascular smooth muscle cell calcification. 1100 70

Cardiac valve calcification (VC) has long been regarded as a consequence of aging and abnormal calcium-phosphate metabolism in uremic patients. In view of the recent recognition of association among inflammation, malnutrition, and atherosclerosis, the possible role of inflammation and malnutrition in VC was investigated. Inflammatory markers (including C-reactive protein [CRP], fibrinogen, and basal metabolic rate) and nutritional status (assessed using serum albumin, subjective global nutrition assessment, and handgrip strength) were examined, in addition to calcium phosphate parameters and other traditional cardiovascular risk factors, including gender, smoking habits, BP, and lipid profile, in relation to VC in 137 patients who were on continuous ambulatory peritoneal dialysis. Compared with patients with no VC, patients with VC not only were older (60 [10] versus 54 [12] yr; P = 0.005), had higher plasma phosphate (1.89 [0.52] versus 1.64 [0.41] mmol/L; P = 0.003), and had higher parathyroid hormone (83 [40, 145] versus 38 [16, 71] pmol/L; P = 0.001) but also had higher CRP (4.5 [0.1, 13.4] versus 0.2 [0.1, 4.4] mg/L; P = 0.004), had higher fibrinogen (6.6 [1.9] versus 5.7 [1.3] g/L; P = 0.002), and had lower serum albumin (26 [4] versus 29 [3] g/L; P = 0004). Twenty-three percent of patients with VC versus 17% of patients with no VC were moderately to severely malnourished according to subjective global nutrition assessment (P = 0.05). Even after adjustment for patients' age, duration of continuous ambulatory peritoneal dialysis, diabetes, and calcium x phosphate product, cardiac VC remained strongly associated with CRP (odds ratio, 1.05; P = 0.026) and albumin (odds ratio, 0.85; P = 0.01). The data suggest that VC not only is a passive degenerative process but also involves active inflammation, similar to that seen in atherosclerosis. The presence of uncontrolled hyperphosphatemia and hyperparathyroidism further accelerates the progression of calcification. The data also indicate that VC and atherosclerosis should be considered as associated syndromes, sharing similar pathogenic mechanisms, namely active inflammation.
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PMID:Association of inflammation and malnutrition with cardiac valve calcification in continuous ambulatory peritoneal dialysis patients. 1151 87

Cardiovascular complications caused by an accelerated atherosclerotic disease represent the largest single cause of mortality in chronic renal failure patients. The rapidly developing atherosclerosis of the uremic syndrome appears to be caused by a synergism of different mechanisms, such as malnutrition, oxidative stress and genetic factors. Recent studies provide evidence that chronic inflammation plays an important role in the pathogenesis of cardiovascular diseases. Hyperphosphatemia and an increased calcium-phosphate ion product have also been associated with an increased risk of death. Cardiovascular calcifications secondary to increases in phosphate and calcium load in dialysis patients might exert an important contribution to the excess cardiovascular mortality and morbidity in dialysis patients. Elevated serum levels of plasma C-reactive protein (CRP) are associated with the extent and severity of the atherosclerotic processes as well as with an increased risk of experiencing myocardial infarction and sudden cardiac death in apparently healthy subjects. In patients affected by pre-dialytic renal failure increased levels of CRP and IL-6 were recorded in 25% of our population; CRP and IL-6 were inversely related with renal function. These data suggest the activation--even in the predialytic phase of renal failure--of mechanisms known to contribute to the enhanced cardiovascular morbidity and mortality of the uremic syndrome. In recent years we have investigated the hypothesis that the chronic inflammatory state of the uremic patient could be at least in part due to the dialytic technique. We have shown that the increase of CRP in stable dialysis patients may be due to the stimulation of monocyte/macrophage by backfiltration of dialysate contaminants. During conventional dialysis, a positive calcium balance and a concomitant inflammatory state may act as cofactors in the development of cardiovascular calcifications. We suggest that this hypothesis should be verified by clinical studies. A reevaluation of the ideal calcium levels in the dialysate is warranted: a neutral intradialytic calcium balance is probably more appropriate, although not easily attainable.
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PMID:Vascular calcifications as a footprint of increased calcium load and chronic inflammation in uremic patients: a need for a neutral calcium balance during hemodialysis? 1185 66

Arteriosclerosis, atherosclerosis and vascular calcification are causally related to the high morbidity and mortality of patients with chronic renal failure. Oxidative stress and carbonyl stress of uremia, dialysis procedure and/or intravenous iron therapy result in AGE (advanced glycation end-product), ALE (advanced lipoxidation end-product) and AOPP (advanced oxidation protein product) formation, favouring together with elevated CRP (C-reactive protein) levels the development of cardiovascular and cerebrovascular complications. Enhanced plasma levels of homocysteine and ADMA (asymmetric dimethylarginine) contribute to this process. In addition, in chronic renal insufficiency hyperphosphatemia and an enhanced calcium x phosphorus ion product are associated with the morbidity and mortality of the patients, particularly in the presence of fetuin deficiency. Phosphorus, AGEs and AOPPs, beside other factors, catalyze the conversion of vascular smooth muscle cells to osteoblast--like cells (particularly in the presence of monocytes/macrophages), resulting in bone matrix protein formation. Other risk factors, such as age, male sex, smoking, hypertension, diabetes, chronic inflammation, insulin resistance or dyslipidemia (enhanced non-HDL-cholesterol) also contribute to the atherosclerotic risk profile of the patient with chronic renal insufficiency. While there is growing understanding of the mechanisms involved in arteriosclerosis, atherosclerosis and vascular calcification in uremia, we are still missing effective therapeutic maneuvers for reduction of excess mortality in uremic patients.
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PMID:[Atherosclerosis and uremia: signifance of non-traditional risk factors]. 1277 74

Cardiovascular diseases are the leading causes of mortality among patients with end-stage renal disease (ESRD), with arterial disease and left ventricular hypertrophy being the two principal factors of the high mortality rate in this population. In addition to traditional risk factors (age, gender, diabetes, hypertension, lifestyle, hyperlipidemia, smoking, hyperhomocystinemia), inflammation, oxidative stress and disorders of mineral metabolism may contribute to cardiovascular risk in patients with uremic syndrome. High serum phosphate may influence vascular calcifications directly and indirectly, by worsening secondary hyperparathyroidism. Several treatment options are available for the treatment of hyperphosphatemia and secondary hyperparathyroidism in patients with ESRD. The treatment approach includes a diet low in phosphorus, with less than 1 g/kg/day of protein. Vitamin D supplementation is an important part of treatment. Phosphate binding agents are in most of the patients necessary in addition to diet. Aluminum hydroxide has been widely used for many years. It is very potent, but also very toxic, with severe encephalopathy as the most dangerous side effect. Calcium salts are less potent, and were considered safe for use in patients on dialysis. However, improvement in the understanding of vascular calcifications has demonstrated that calcium overload significantly contributes to widespread atherosclerosis in patients with ESRD. Sevelamer-hydrochloride is a novel non-aluminum, non-calcium containing phosphate binder, which is capable of reducing the levels of phosphorus as well as of low-density lipoprotein cholesterol, and increasing high-density lipoprotein cholesterol.
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PMID:[Hyperphosphatemia and cardiovascular risk in patients on dialysis]. 1550 84

Patients with end-stage renal disease have greatly elevated risks of atherosclerotic disease. Vascular calcification in advanced atherosclerosis is a common feature in ESRD patients. Risk factors of atherosclerosis in ESRD patients are coronary risk factors such as hypertension, diabetes and hyperlipidemia and hyperphosphatemia. Bone associated proteins including osteopontin, matrix Gla protein and osteoprotegerin may be involved in the progression of atherosclerosis.
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PMID:[Risk factors of atherosclerosis in end-stage renal disease patients]. 1557 49

Cardiovascular disease is the largest cause of mortality in hemodialysis patients. Cardiovascular mortality is fivefold to twentyfold higher in hemodialysis patients than in the general population. Atherosclerosis and vascular calcification are the characteristic complications in hemodialysis patients. Hemodialysis patients have traditional risk factors such as abnormal lipid metabolism and uremia-related risk factors such as oxidative stress and hyperphosphatemia. Oxidative stress takes place by increased production of oxidants by leukocytes and antioxidant loss of vitamin C and E. Oxidatively modified LDL exist in the circulation by excess of oxidative stress in hemodialysis patients. Oxidative stress is a major contributor to accelerated development atherosclerosis. Oxidative stress and hyperphosphatemia also influence vascular calcification. The pattern of vascular calcification in hemodialysis patient is characterized by mineral deposition in the tunica media. It is reported that the obvious calcification in aorta and artery of the MGP knockout mouse is recognized. It is indicated that MGP has the inhibitory effect of the calcification of vessel wall. Vitamin E protects atherosclerosis and vascular calcification in hemodialysis patients. It is also important to control hyperphosphatemia for vascular calcification.
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PMID:[Atherosclerosis and vascular calcification in hemodialysis patients]. 1557 60

Vascular calcification is a common finding in atherosclerosis and a serious problem in uremic patients. Because of the correlation of hyperphosphatemia and vascular calcification, the ability of extracellular inorganic phosphate levels to regulate human aortic smooth muscle cell (HSMC) culture mineralization in vitro was examined. HSMC cultured in media containing normal physiologic levels of inorganic phosphate (1.4 mM) did not mineralize. In contrast, HSMC cultured in media containing phosphate levels comparable with those seen in hyperphosphatemic individuals (>1.4 mM) showed dose-dependent increases in mineral deposition. Mechanistic studies showed that elevated phosphate treatment of HSMC also enhanced the expression of the osteoblastic differentiation markers osteocalcin and osf2/Cbfa-1. The effects of elevated phosphate on HSMC were mediated by a sodium-dependent phosphate cotransporter (NPC) as indicated by the ability of the specific NPC inhibitor phosphonoformic acid to dose-dependently inhibit phosphate-induced calcium deposition as well as osteocalcin and Cbfa-1 gene expression. The NPC in HSMC was identified as Pit-1, a member of the novel type III NPCs. These data suggest that elevated phosphate may directly stimulate HSMC to undergo phenotypic changes that predispose to calcification and offers a novel explanation of the phenomenon of vascular calcification under hyperphosphatemic conditions. Furthermore, we examined the factors affecting peripheral vascular calcification in 332 nondiabetic hemodialysis patients. There were 45 nondiabetic patients with vascular calcification. In multivariate logistic regression, the significant factors affecting vascular calcification were advanced age, longer duration of hemodialysis, increased phosphate concentrations, male gender, and lower predialysis diastolic pressure. Our findings suggest that an elevated phosphate level may directly stimulate HSMC to undergo phenotypic changes that predispose to calcification and offer a novel explanation of the phenomenon of vascular calcification under hyperphosphatemic conditions.
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PMID:Hyperphosphatemia and vascular calcification in end-stage renal disease. 1564 30


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