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)

Hemodialysis patients often experience muscle weakness, cardiac arrhythmias, and hypertriglyceridemia, along with other conditions that may lead to atherosclerosis and coronary heart disease. A contributing factor in the etiology of the symptoms may be carnitine deficiency. Patients undergoing renal dialysis treatment are at risk for developing a carnitine deficiency. The small carnitine molecule can be easily lost into the dialysate. A diseased kidney may lead to a decrease in the endogenous supply of carnitine since the kidney is a major site of carnitine biosynthesis. The diet of dialysis patients may be limiting in preformed carnitine as well as in the precursors and micronutrients required for carnitine biosynthesis. Both oral and intravenous supplementation of L-carnitine have been shown to alleviate muscle weakness, reduce the incidence and severity of arrhythmias, and decrease plasma triglyceride levels, along with alleviating other complications noted in dialysis patients. Health care professionals must be aware of the possible benefits of providing carnitine supplementation for renal dialysis patients.
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PMID:Carnitine nutriture of dialysis patients. 370 Sep 27

51 chronic haemodialysis patients with hypertriglyceridaemia were given a daily oral dose of 2.4 g D,L-carnitine for 30 days to investigate a possible hypolipaemic effect. After 30 days' D,L-carnitine treatment the mean (+/- SEM) serum triglyceride concentration had decreased significantly from 3.50 +/- 0.39 to 2.87 +/- 0.27 mmol/l. Serum total cholesterol did not change. However, HDL cholesterol increased significantly from 0.89 +/- 0.05 to 1.35 +/- 0.07 mmol/l. This decrease in serum triglycerides and return of HDL cholesterol to normal levels in haemodialysis patients may be the result of correction of carnitine deficiency. Such treatment could reduce the risk factors for atherosclerosis and coronary-artery disease in uraemic patients.
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PMID:Carnitine improves lipid anomalies in haemodialysis patients. 610 51

Carnitine ester hydrolysis was observed in homogenates of normal rabbit (Oryctolagus cuniculus) aortas and in intact aortas from normal and cholesterol-fed rabbits using [14C]palmitoylcarnitine as a substrate. Hydrolytic activity was decreased approximately 50% in arterial tissue from cholesterol-fed rabbits and may account for the observation that carnitine esters accumulate in arteries of animals fed atherogenic diets. Long-chain acylcarnitines (C14-C18) were found to be moderate inhibitors of microsomal acylCoA:cholesterol acyltransferase (ACAT, EC 2.3.1.26); short-chain acylcarnitine (C2-C10) and carnitine itself were not inhibitors. The data suggest that the increase in activity of arterial ACAT that characteristically parallels the development of atherosclerosis does not occur as a result of carnitine ester accumulation.
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PMID:Carnitine ester hydrolysis in arteries from normal and cholesterol-fed rabbits and the effects of carnitine esters on arterial microsomal ACAT. 650 6

We have characterized the extent and the phenotype of total and proliferating cell population of aortic plaques in aged rabbits receiving a long-term low-dose cholesterol hyperlipemic diet, which represents an experimental model of atherosclerosis. For nine months, rabbits received the hypercholesterolemic diet alone or in addition to a treatment with propionyl-L-carnitine (PLC), a derivative of carnitine, an intramitochondrial carrier of fatty acids present in most cell types. We observed that, in both PLC-treated and control hyperlipemic rabbits, the ratio between proliferating macrophage-derived and smooth muscle cells was 2:1. PLC in addition to the hypercholesterolemic diet induced a marked lowering of plasma triglycerides, very low density lipoprotein (VLDL) and intermediate density lipoprotein (IDL) triglycerides, while plasma cholesterol was slightly and transiently reduced. Moreover, PLC-treated hyperlipemic rabbits exhibited a reduction of plaque thickness and extent, a slight but significant reduction of the percentage of macrophage-derived cells as compared to control hyperlipemic animals and a reduction of the number of both proliferating macrophage- and smooth muscle cell-derived foam cells. Finally, both proliferating and non-proliferating plaque cells expressed large amounts of macrophage colony-stimulating factor protein, in particular macrophage-derived foam cells. These results indicate that a modification of plasma lipemic pattern obtained by a long-term oral administration of PLC was associated with a decrease of plaque cell proliferation and severity of aortic atherosclerotic lesions.
Atherosclerosis 1995 Apr 07
PMID:Propionyl-L-carnitine prevents the progression of atherosclerotic lesions in aged hyperlipemic rabbits. 760 74

Several authors have supplemented patients submitted to the hemodialytic treatment with L-carnitine, with the aim to affect the lipid profile often unfavourably altered in these patients. Different doses of the compound have been employed and the outcome in plasma lipid changes is very dissimilar. Some authors have reported favourable changes, some have not observed any effect, some have reported a worsening of the lipids profile. A review of the data so far available may allow some considerations on the suitability of using L-carnitine in order to affect favourably the progress of accelerated atherosclerosis.
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PMID:Carnitine and lipid profile in uremia. 937 58

Lipid peroxides are considered to be the initiation factor for atherosclerosis. Present study depicts that L-carnitine treatment (300 mg/kg body weight/day) for 7 and 14 days caused significant reduction in the tissue lipid peroxidations. It also shows marked improvement in the antioxidant status. By this way carnitine maintain the normal function of the cells.
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PMID:Protective role of L-carnitine on liver and heart lipid peroxidation in atherosclerotic rats. 1138 42

Peripheral arterial disease affects approximately 8-10 million people in the United States. Approximately one-third to one-half of these individuals are symptomatic. The risk factors that contribute to peripheral arterial disease are similar to those associated with other forms of atherosclerosis, including diabetes mellitus, cigarette smoking, hypercholesterolemia, high blood pressure, and hyperhomocysteinemia. Of these, diabetes and cigarette smoking pose the greatest risk for developing peripheral arterial disease. The prognosis of patients with these risk factors is limited because of their greater risks for myocardial infarction, stroke, and cardiovascular death. Cardiovascular mortality correlates inversely with the ankle/brachial index, and the risk of death is greatest in those with the most severe peripheral arterial disease. Treatment regimens to reduce cardiovascular morbidity and mortality in patients with peripheral arterial disease should include risk factor modification and antiplatelet therapy. The cardinal symptoms of peripheral arterial disease include intermittent claudication and rest pain, with the latter being indicative of critical limb ischemia. Therapeutic strategies that focus on improving the patient's quality of life, reducing the severity of claudication, and improving limb viability include supervised exercise training, pharmacotherapy, and revascularization. Two drugs-pentoxifylline and cilostazol-currently are approved by the Food and Drug Administration for the treatment of patients with claudication. Meta-analyses have suggested that, compared with placebo, pentoxifylline improves maximal walking distance by approximately 20-25%. Cilostazol is a phosphodiesterase type 3 inhibitor. In clinical trials, cilostazol has consistently improved maximal walking distance as compared with placebo, with the range of improvement being approximately 40-60%. Drugs that are currently under investigation include propionyl-L-carnitine, vasodilator prostaglandins, L-arginine, and the angiogenic factors, vascular endothelial growth factor and basic fibroblast growth factors.
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PMID:Medical management of peripheral arterial disease. 1140 4

This study has been initiated to investigate, in hypercholesterolaemic rabbits, whether L-carnitine deficiency could be an additional risk factor in atherosclerosis, and if so, whether L-carnitine supplementation could prevent the progression of atherosclerosis. Hypercholesterolaemia was induced by feeding rabbits 2% cholesterol-enriched diet for 28 days, whereas, carnitine deficiency was induced by daily i.p. administration of 250 mg kg(-1) of D-carnitine for 28 days. Histopathological examination of aorta and coronaries from hypercholesterolaemic rabbits revealed severe atherosclerotic lesions, intimal plaques and foam cell formation. Also, hypercholesterolaemic diet resulted in a significant 53 and 43% decrease in reduced glutathion (GSH) levels and a significant (1.87-fold) and (14.1-fold) increase in malonedialdhyde (MDA) levels in aorta and cardiac tissues, respectively. Daily administration of L-carnitine (250 mg kg(-1)) for 28 days, completely prevented the progression of atherosclerotic lesions induced by hpercholesterolaemia in both aorta and coronaries. Conversely, daily administration of D-carnitine (250 mg kg(-1)) for 28 days increased the progression of atherosclerotic lesions with the appearance of foam cells and apparent intimal plaques which are even larger than that seen in hypercholesterolaemic rabbits. Both L-carnitine and D-carnitine produced similar effects on the lipid profile, GSH and MDA which may point to the conclusion that: (1) L-carnitine prevents the progression of atherosclerotic lesions by another mechanism in addition to its antioxidant and lipid-lowering effects; (2) endogenous carnitine depletion and/or carnitine deficiency should be viewed as an additional risk factor in atherogenesis.
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PMID:L-carnitine prevents the progression of atherosclerotic lesions in hypercholesterolaemic rabbits. 1152 91

Previously we documented that propionyl-L-carnitine (PLC) reduces the growth of atherosclerotic lesions in cholesterol-fed aged rabbits in association with a decrease of plaque smooth muscle cell (SMC) proliferation and plasma triglycerides. To clarify whether PLC might influence SMC growth through mechanisms other than triglyceride lowering, we investigated the effect of a daily treatment per os with PLC on carotid intimal hyperplasia after ballooning in normocholesterolemic rabbits. PLC did not induce variations of plasma triglyceride and cholesterol. One week later, the number of proliferating SMCs was reduced in PLC as compared with controls. After 3 weeks, morphometric analysis demonstrated a reduced neointimal relative volume and percentage of stenosis but not vessel area in PLC as compared with controls. This associated with an intimal reduced SMC number and an increased apoptotic rate as detected by nick-end labelling (TUNEL) and ligation-mediated polymerase chain reaction (PCR). Western blotting also demonstrated an increase of caspase-3 cleavage in PLC carotids. Antiproliferative and pro-apoptotic effects of PLC were confirmed in vitro on actively proliferating and serum deprived SMCs, respectively. Molecules with an additional cell-specific, pro-apoptotic action may represent a new therapeutic tool in reducing intimal SMC hyperplasia following angioplasty or stenting procedures.
Atherosclerosis 2002 Jan
PMID:Propionyl-L-carnitine reduces intimal hyperplasia after injury in normocholesterolemic rabbit carotid artery by modulating proliferation and caspase 3-dependent apoptosis of vascular smooth muscle cells. 1175 25

The bioincompatibility of dialytic systems along with the loss of antioxidant substances via the dialysis may contribute to peripheral blood mononuclear cell (PBMC) activation and the production of inflammatory mediators, such as cytokines, oxygen radicals, and complement fragments, that may sustain a state of chronic microinflammation responsible for the pathogenesis of a variety of diseases, including atherosclerosis, anemia, and malnutrition. Moreover, during hemodialysis (HD), oxidative stress may influence several intracellular signaling enzymes, including some stress-activated kinases, such as jun-N-terminal kinase (JNK), potentially leading to PBMC activation and proinflammatory cytokine production. Recent reports suggest that L-carnitine may play an important role in balancing antioxidative systems. Therefore, we sought to evaluate the effect of L-carnitine supplementation on the PBMC responses to oxidative stress induced by different HD membranes. We observed in PBMC from cellulosic (C)-treated patients an increase in the amount of intracellular tyrosine-phosphorylated proteins and a striking activation of JNK, as compared with synthetic (S)-treated patients. On the contrary, 3 months of L-carnitine supplementation significantly lowered intracellular levels of phosphorylated proteins and JNK activity in PBMC from C-treated patients. In addition, after 180 minutes of HD, a significant decrease in global plasma antioxidant capacity was found, particularly in C-treated patients, whereas L-carnitine supplementation improved plasma antioxidant capacity levels in these patients. These observations were also confirmed by in vitro experiments, showing the ability of L-carnitine to reduce the JNK activation in normal PBMC exposed to different amounts of hydrogen peroxide. In conclusion, the uremic milieu is characterized by an enhanced inflammatory response and an increased oxidant load, affecting lipids, carbohydrates, and proteins. Regular L-carnitine supplementation in HD patients can improve cellular defense against chronic inflammation and oxidative stress, most likely by modulating the specific signal transduction cascade activated by an overproduction of proinflammatory cytokines and oxidative stress.
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PMID:Inflammation and carnitine in hemodialysis patients. 1564 99


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