Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fatty acid metabolism is abnormal in insulin-resistant states that increase the risk of atherosclerosis such as type 2 diabetes and the metabolic syndrome. How fatty acids promote vascular disease is poorly understood, but lipoprotein lipase and peroxisome proliferator-activated receptor alpha (PPARalpha)-physiologically related proteins involved in fatty acid metabolism-may be involved. Glucocorticoid metabolism is also abnormal in insulin-resistant states and may promote several components of the metabolic syndrome. Recent studies have shown that hepatic fatty acid metabolism is required for the development of insulin resistance and hypertension caused by glucocorticoid excess, suggesting that crosstalk between glucocorticoid receptor-and PPARalpha-dependent pathways may contribute to vascular disease.
 ...
PMID:Fatty acid metabolism and vascular disease. 1503 Jul 93

The many effects that the oestrogens and progestagens used in oral contraceptive (OC) and postmenopausal hormone replacement therapies (HRTs) have on lipoprotein metabolism are of importance because of the involvement of lipoproteins in endothelial damage and arterial occlusion. Lipoproteins promoting endothelial damage include: low density lipoprotein (LDL), particularly the small dense subfraction (sdLDL), remnants of very low density lipoprotein (VLDL) and chylomicron metabolism, and lipoprotein (a). High density lipoprotein (HDL) has pleiotropic effects that prevent or alleviate endothelial damage. Orally administered oestrogens increase hepatic triglyceride synthesis and VLDL secretion and increase the proportion of sdLDL. Oestrogens increase the rates of elimination of LDL, VLDL remnants and chylomicrons, suppress the synthesis of key enzymes of lipoprotein metabolism, hepatic and lipoprotein lipase, and increase synthesis of the principal apoprotein of HDL, apoAI. In general, progestagens oppose these effects according to type and dose. In OC and HRT users, this leads to a range of different lipoprotein profiles, which may differ from those evaluated with respect to vascular disease risk in population studies. Accumulating evidence suggests that the clinical implications of steroid induced changes in the lipoprotein profile will need to be evaluated independently of population-based evidence.
 ...
PMID:Biology: risk factor modification by OCs and HRT lipids and lipoproteins. 1506 83

The long-term success of cardiac allograft transplantation is limited by the development of a particular type of coronary atherosclerosis referred to as transplant vascular disease (TVD). Although the exact pathogenesis of TVD remains to be established, there is growing evidence that TVD involves immunological mechanisms operating in a milieu of nonimmunological risk factors. These immunological events constitute the principal initiating stimuli, resulting in endothelial injury with consequent myointimal hyperplasia, extracellular matrix synthesis and invocation of proteoglycan (PG)-lipoprotein interactions, leading, ultimately, to lipid retention in the vessel wall. The profound early 'insudation' of apolipoproteins along with uncertain endothelial 'intactness' in human coronary arteries in the transplanted heart, suggest that permeability of these vessel walls must be altered. Further, frequent and typically diffuse intracellular and extracellular accumulation of lipids and PGs in both the intimal and medial layers of cardiac allograft arteries has affirmed that the alloimmune environment accompanied with aberrant expression of extracellular matrix components, especially PGs, may strongly promote lipid imbibition in the allograft vascular bed, leading to TVD. In summary, the cumulative data support the view that profound lipid accumulation occurs in allograft arteries beginning very early post-transplantation, contributing to intimal thickening; that lipoproteins enter and are trapped in the subendothelial tissue, apparently through interactions with PGs; that with direct glycosaminoglycans, apolipoprotein interactions may occur, or they may occur through bridging molecules like phospholipase A2 and lipoprotein lipase; and that prolonged residence in the intima leads to lipoprotein modification, with subsequent modulation of biological processes that promote atherogenesis.
 ...
PMID:Transplant vascular disease: role of lipids and proteoglycans. 1583 69

Cholesteryl ester transfer protein (CETP) and lipoprotein lipase (LPL) are both key players in plasma lipoprotein homeostasis and, as such, genetically induced alterations in their respective activities may affect susceptibility to cerebrovascular diseases. In this study, we examined the distribution of two common polymorphisms, namely CETP TaqI B and LPL Ser447Ter in a cohort of Greek clinically diagnosed late-onset ischaemic stroke patients (n = 98) and an ethnicity-, age- and sex-matched control group with no manifestations of vascular disease (n = 100). Our study revealed no statistically significant differences with respect to the distribution of either polymorphism, examined separately or in combination, between the two groups.
 ...
PMID:Cholesteryl ester transfer protein TaqI B and lipoprotein lipase Ser447Ter gene polymorphisms are not associated with ischaemic stroke in Greek patients. 1589 5

Hypertriglyceridemia is an important pathophysiologic feature of preeclampsia, a common vascular disorder of pregnancy. Three well-documented functional variants (N291S, S447X, and D9N) of the lipoprotein lipase gene were related to hypertriglyceridemia. Results from the only two studies concerning the relationship between these variants and preeclampsia risk have been inconsistent. We investigated this relationship in a case-control study including 144 preeclamptic and 290 normotensive pregnant women (all non-Hispanic Caucasians). We estimated odds ratios (OR) and 95% confidence intervals (CI) adjusted for maternal age, pre-pregnancy body mass index, and parity. After adjusting for covariates, women with the 291 N/S or S/S genotype had significantly increased risk of preeclampsia (OR 6.9, 95% CI 1.9-25.4) compared with women with the common 291N/N genotype. The 447 S/X or X/X genotype was not significantly associated with preeclampsia risk. The frequency of the 9N variant allele was 1.8% in controls, while this allele was not observed among cases. Haplotype 9D/291S/447S was strongly associated with higher risk of preeclampsia as compared with the most common haplotype 9D/291N/447S (adjusted OR 6.6, 95% CI 1.7-25.0). Results from our study support the thesis that abnormal lipid metabolism is important in the pathogenesis of preeclampsia.
 ...
PMID:Functional variants of the lipoprotein lipase gene and the risk of preeclampsia among non-Hispanic Caucasian women. 1645 Nov 34

Tyloxapol (Triton WR 1339) is a non-ionic detergent that inhibits lipoprotein lipase and thereby raises levels of serum lipids. It is used frequently for acute studies on lipids in rats but not for subacute or chronic studies. In the present work, we found that tyloxapol must be injected intravenously three times each week in order to have high and sustained levels of serum cholesterol and triglycerides for 1, 2, or 3 weeks. These results make it possible to extend the use of tyloxapol into chronic studies of hyperlipemia and vascular disease.
 ...
PMID:A procedure for inducing sustained hyperlipemia in rats by administration of a surfactant. 1683 86

Metabolic syndrome is associated with insulin resistance and atherosclerosis. Here, we show that deficiency of one or two alleles of ATM, the protein mutated in the cancer-prone disease ataxia telangiectasia, worsens features of the metabolic syndrome, increases insulin resistance, and accelerates atherosclerosis in apoE-/- mice. Transplantation with ATM-/- as compared to ATM+/+ bone marrow increased vascular disease. Jun N-terminal kinase (JNK) activity was increased in ATM-deficient cells. Treatment of ATM+/+apoE-/- mice with low-dose chloroquine, an ATM activator, decreased atherosclerosis. In an ATM-dependent manner, chloroquine decreased macrophage JNK activity, decreased macrophage lipoprotein lipase activity (a proatherogenic consequence of JNK activation), decreased blood pressure, and improved glucose tolerance. Chloroquine also improved metabolic abnormalities in ob/ob and db/db mice. These results suggest that ATM-dependent stress pathways mediate susceptibility to the metabolic syndrome and that chloroquine or related agents promoting ATM activity could modulate insulin resistance and decrease vascular disease.
 ...
PMID:ATM-dependent suppression of stress signaling reduces vascular disease in metabolic syndrome. 1708 7

Chronic kidney disease (CKD) is associated with dyslipidemia, characterized by increased levels of triglyceride-rich lipoproteins (TRLPs), including very low-density lipoprotein (VLDL) and intermediate-density lipoprotein (IDL), with no change or a reduction in low-density lipoprotein (LDL) and low high-density lipoprotein (HDL) levels. Serum triglycerides and IDL are risk factors for vascular disease in dialysis patients, whereas LDL is not. The principal cause of the increase in TRLPs is decreased removal, not increased synthesis. The clearance defect arises from a reduction in specific lipoprotein receptors, decreases in the activity of lipases, and increased levels of low-molecular weight apolipoproteins that inhibit the interaction between TRLPs and both the receptors and the lipases that catabolize them. VLDL from dialysis patients is structurally abnormal and is not metabolized at a normal rate by lipoprotein lipase (LPL).
 ...
PMID:Dialysis removes apolipoprotein C-I, improving very low-density lipoprotein clearance. 1766 86

High-density lipoproteins (HDL) contain approximately 25% of the cholesterol and <5% of the triglyceride in the plasma of human blood. However, the dynamic exchange of lipids and lipid-binding proteins is not revealed by simply considering the mass of material at any point in time. HDL are the most complex of lipoprotein species with multiple protein constituents, which facilitate cholesterol secretion from cells, cholesterol esterification in plasma, and transfer of cholesterol to other lipoproteins and to the liver for excretion. They also play a major role in triglyceride transport by providing for activation of lipoprotein lipase, exchange of triglyceride among the lipoproteins, and removal of triglyceride rich remnants of chylomicrons and very-low-density lipoproteins after lipase action. In addition, antioxidative enzymes and phospholipid transfer proteins are important components of HDL. Many of the proteins of HDL are exchangeable with other lipoproteins, including chylomicrons and very-low-density lipoproteins. The constantly changing content of lipids and apolipoproteins in HDL particles generate a series of structures that can be analyzed by using separation techniques that depend on size or charge of the particles. Interaction of these various structures can be very different with cell surfaces depending on the size or apolipoprotein content. A series of different transport proteins preferentially exchange lipids with specific structures among the HDL but interact poorly or not at all with others. The role of these differing forms of HDL and their interactions with cells and other lipoprotein species in plasma is the subject of intense study stimulated by the potential for reducing atherogenesis. The strength of this is only partially indicated by the correlation of higher total levels of the HDL particles with reduced incidence of vascular disease in various clinical trials and epidemiological studies.
 ...
PMID:High-density lipoprotein and transport of cholesterol and triglyceride in blood. 2129 64

Type III hyperlipoproteinemia (type III HLP) rarely manifests in childhood. Long-term follow-up (37 years) of the first patient revealed hypothyroidism at diagnosis requiring thyroxine replacement, palmar xanthomas requiring surgical removal, splenomegaly requiring splenectomy, 18 episodes of pancreatitis and premature coronary artery disease. Investigation revealed an apolipoprotein E phenotype of E2/E2 and partial lipoprotein lipase deficiency. Investigation of the second patient revealed a combination of apoE2/E2 phenotype and heterozygous familial hypercholesterolaemia. The third patient had a complete deficiency of lipoprotein lipase activity, an abnormal thyroid stimulating hormone on diagnosis (with subsequent normalisation without treatment), and apoE2/E2 phenotype. Type III HLP is a serious disorder with lifelong consequences of premature vascular disease and recurrent pancreatitis. Early presentation of disease in our patients was associated with additional precipitating factors. Drug treatment of paediatric type III HLP is indicated if dietary modifications alone are insufficient in managing the dyslipidaemia.
 ...
PMID:Case series of type III hyperlipoproteinemia in children. 2269 86


<< Previous 1 2 3 4 Next >>