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

The contents of three species of proteoglycans (PGs), heparan sulfate PG(HSPG), chondroitin sulfate PG(CSPG) and dermatan sulfate chondroitin sulfate PG(DSCSPG), in human thoracic aortas of subjects from districts of high (Beijin, in North China) and low (Nanning, in South China) prevalence of atherosclerosis in China were quantitated. Higher aortic HSPG and DSCSPG (but lower DS) in samples from Nanning than those from Beijing might be implicated in the lower prevalence of atherosclerosis in the former.
Atherosclerosis 1991 Jan
PMID:Human aortic proteoglycans of subjects from districts of high and low prevalence of atherosclerosis in China. 190 31

From 1986 to 1989, 324 aortae from accidental death aged 15-39 were collected from two locations, one of higher prevalence (Beijing in North China), and the other of lower prevalence (Nanning in South China) of atherosclerosis (AS) and coronary heart disease (CHD). Morphometry and biochemical analyses, were used in the study with emphasis on the changes of smooth muscle cells (SMC) in the aortic intima and on the aortic proteoglycans (PGs) of specimens from both locations to elucidate their relationship with the pathogenesis and development of AS and to find ways, if any, for the prevention and control of AS. The results showed that the densities, especially the area density of the cell nuclei of aortic SMC were significantly higher in specimens from the North than those from the South (P < 0.01). Nuclear densities of SMC negatively correlated with alcian blue-positive substances; both total PGs and Heparin sulfate PG (HSPG, inhibitory to SMC proliferation) of the aortic intima and media were lower in specimens from the North than those from the South (P < 0.01). The percentage of sudanophilic lesion (SL) in the total intimal area, showing the extent of fatty infiltration of aortae from the two locations, was similar except that of the male abdominal aortae which was higher in the North (P < 0.01). The above findings showed that decreased content of HSPG which is inhibitory to SMC proliferation might be one of the causes of the augmentation of aortic SMC proliferation in Beijing specimens; and also the increased serum cholesterol concentration of the population in Nanning was reflected in the SL of the aortic intima.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The influence of age and location of arterial lesion on the pathogenesis and development of early atherosclerotic lesions in youth. 808 76

HB-EGF is a heparin-binding member of the EGF family that was initially identified in the conditioned medium of human macrophages. Soluble mature HB-EGF is proteolytically processed from a larger membrane-anchored precursor and is a potent mitogen and chemotactic factor for fibroblasts, smooth muscle cells but not endothelial cells. HB-EGF activates two EGF receptor subtypes, HER1 and HER4 and binds to cell surface HSPG. The transmembrane form of HB-EGF is a juxtacrine growth and adhesion factor and is uniquely the receptor for diphtheria toxin. HB-EGF gene expression is highly regulated, for example by cytokines, growth factors, and transcription factors such as MyoD. HB-EGF has been implicated as a participant in a variety of normal physiological processes such as blastocyst implantation and wound healing, and in pathological processes such as tumor growth, SMC hyperplasia and atherosclerosis.
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PMID:Heparin-binding EGF-like growth factor. 942 3

Type III hyperlipoproteinemia (HLP) is a genetic disorder characterized by accumulation of remnant lipoproteins in the plasma and development of premature atherosclerosis. Although receptor binding-defective forms of apolipoprotein (apo) E are the common denominator in this disorder, a number of apparent paradoxes concerning its pathogenesis still exist. However, studies in transgenic animals are resolving the mechanisms underlying this disorder. PARADOX I: Defective apoE (commonly apoE2) is essential but not sufficient to cause overt type III HLP. In fact, most apoE2 homozygotes are hypolipidemic. Studies in apoE2 transgenic models have demonstrated the impact of other genes or hormones in converting the hypolipidemia to hyperlipidemia. PARADOX II: Among apoE2 homozygotes, men are more susceptible than women to type III HLP. Transgenic studies have shown that estrogen affects both LDL receptor expression and lipolytic processing, explaining the resistance of women to this disorder until after menopause. PARADOX III: ApoE deficiency is associated with hypercholesterolemia, whereas the type III HLP phenotype is characterized by both hypercholesterolemia and hypertriglyceridemia. The hypercholesterolemia is caused by impaired receptor-mediated clearance, whereas the hypertriglyceridemia is caused primarily by impaired lipolytic processing of remnants and increased VLDL production associated with increased levels of apoE. PARADOX IV: ApoE2 is associated with recessive inheritance of this disorder, whereas other defective apoE variants are associated with dominant inheritance. Determinants of the mode of inheritance are the differential binding of apoE variants to the LDL receptor versus the HSPG/LRP complex and the preference of certain apoE variants for specific lipoproteins. Thus, the pathogenesis of this sometimes mysterious disorder has been clarified.
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PMID:Pathogenesis of type III hyperlipoproteinemia (dysbetalipoproteinemia). Questions, quandaries, and paradoxes. 1055 97

The excess of glucose appears to play an important and specific role in the genesis of macroangiopathy in diabetics. Activation of protein kinase-C, the sorbitol pathway, and AGE formation are thought to be the major pathways linking the degree of glycaemic compensation with the pathogenetic process of macrovascular disease. HSPG is likely to be a key element in this process since it is a regulator of endothelial permeability, vascular antithrombotic capacity, insulin sensitivity (with respect to lipoprotein lipase availability), and vascular extracellular matrix content and smooth-muscle-cell activation. Loss of HSPG is suggested clinically by the presence of microalbuminuria, to the development of which diabetic control also contributes significantly. However, genetic factors also seem to be involved. Much more insight into the precise mechanismus is necessary to unravel the cellular and molecular chains of events for the premature and accelerated atherosclerosis in diabetic patients.
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PMID:The atherosclerotic process and its exacerbation by diabetes. 1146 May 93

Human apolipoprotein E (apoE) consists of a single polypeptide chain with 299 amino acids and is best known for its role in the transport of cholesterol and other lipids between peripheral tissues and the liver. However, more direct effects of apoE on the vascular wall may well contribute to arterial protection from atherosclerosis. This review will focus on: (a) the ability of apoE to direct cholesterol efflux mechanisms with the aid of apoA1 and the ATP binding cassette transporter 1 (ABC1); (b) the ability of apoE to prevent platelet aggregation by facilitating the production of endogenous nitric oxide (NO); (c) the ability of apoE to inhibit the proliferation of T-lymphocytes by internalization of the IL-2 receptor; and (d) the ability of apoE to inhibit proliferation of endothelial cells by out competing growth factors for interaction with cell surface heparan sulfate proteoglycans (HSPG's). The characterization of apoE and its many functions has provided insight into the ultimate potential of this protein as a possible therapeutic agent for the treatment of atherosclerosis. This review will examine key scientific advances, which focus on possible therapeutic strategies that encompass the use of apoE in the amelioration of atherosclerosis.
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PMID:Apolipoprotein E: possible therapeutic target for atherosclerosis. 1276 59

Hyperglycemia is an independent risk factor for diabetes-associated cardiovascular disease. One potential mechanism involves hyperglycemia-induced changes in arterial wall extracellular matrix components leading to increased atherosclerosis susceptibility. A decrease in heparan sulfate (HS) glycosaminoglycans (GAG) has been reported in diabetic arteries. The present studies examined the effects of high glucose on in vitro production of proteoglycans (PG) by aortic endothelial cells. Exposure of cells to high glucose (30 vs. 5 mM glucose) resulted in decreased [(35)S] sodium sulfate incorporation specifically into secreted HSPG. Differences were not due to hyperosmolar effects and no changes were observed in CS/DSPG. Enzymatic procedures, immunoprecipitation and Western analyses demonstrated that high glucose induced changes specifically in the HSPG, perlecan. In double-label experiments, lower sulfate incorporation in high-glucose-treated cells was accompanied by lower [(3)H] glucosamine incorporation into GAG but not lower [(3)H] serine incorporation into PG core proteins. Size exclusion chromatography demonstrated that GAG size was unchanged and GAG sulfation was not reduced. These results indicate that the level of regulation of perlecan by high glucose is posttranslational, involving a modification in molecular structure, possibly a decrease in the number of HS GAG chains on the core protein.
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PMID:High-glucose-induced structural changes in the heparan sulfate proteoglycan, perlecan, of cultured human aortic endothelial cells. 1505 91

Both extracellular superoxide dismutase (EC-SOD) and heparin binding EGF like growth factor (HB-EGF) are produced in smooth muscle cells of the arterial wall, and are thought to play pathological roles in atherosclerosis with heparin binding characteristics. EC-SOD treatment clearly reduced the H2O2 induced expression of HB-EGF in rat aortic smooth muscle cells (RASMC). EC-SOD also inhibited the induction of HB-EGF by 12-O-tetradecanoylphorbol-13-acetate (TPA) in RASMC by 60%. Both H2O2 and TPA increased intracellular ROS levels, and EC-SOD inhibited ROS generation only for the case of H2O2 but not TPA. Treatment of the cells with heparin alone decreased HB-EGF expression by 20%, whereas EC-SOD alone and a co-incubation with EC-SOD and heparin suppressed the induction by 60 and 70%, respectively. These results suggest that EC-SOD is related to the EGF signaling in two ways, competition for HSPG with HB-EGF and as an ROS scavenger.
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PMID:Inhibition of gene expression of heparin-binding epidermal growth factor-like growth factor by extracellular superoxide dismutase in rat aortic smooth muscle cells. 1675 36