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 abnormal proliferation of aortic vascular smooth muscle cells (VSMCs) plays a central role in the pathogenesis of atherosclerosis and restenosis after angioplasty and possibly also in the development of hypertension. The present study was designed to examine the inhibitory effects and the mechanism of luteolin 7-glucoside (L7G) on the platelet-derived growth factor (PDGF)-BB-induced proliferation of VSMCs. L7G significantly inhibited the PDGF-BB-induced proliferation and the DNA synthesis of the VSMCs in a concentration-dependent manner. Pre-incubation of the VSMCs with L7G significantly inhibited the PDGF-BB-induced extracellular signal-regulated kinase 1/2 (ERK1/2), Akt and the phospholipase C (PLC)-gamma1 activation. However, L7G had almost no affect on the phosphorylation of PDGF-beta receptor tyrosine kinase, which was induced by PDGF-BB. These results suggest that L7G inhibits the PDGF-BB-induced proliferation of VSMCs via the blocking of PLC-gamma1, Akt, and ERK1/2 phosphorylation.
 ...
PMID:The inhibitory effect and mechanism of luteolin 7-glucoside on rat aortic vascular smooth muscle cell proliferation. 1649 46

Advanced glycation end products (AGEs) play a significant role in the pathophysiology of diabetes leading to such conditions as atherosclerosis, cataract formation, and renal dysfunction. While the formation of nucleoside AGEs was previously demonstrated, no extensive studies have been performed to assess the effect of AGEs on DNA structure and folding. The objective of this study was to investigate the nonenzymatic glycation of two DNA oligonucleotide duplexes with one duplex consisting of deoxy-poly(A)15 and deoxy-poly(T)15 and the other consisting of deoxy-poly(GA)15 and deoxy-poly(CT)15. With D-glucose, D-galactose, D/L-glyceraldehyde, and D-glucosamine serving as the model glycating carbohydrates, D-glucosamine was found to exhibit the greatest effect on the stability and structure of the oligonucleotide duplexes, a finding that was confirmed by circular dichroism. The nonenzymatic glycation of deoxy-poly(AT) by D-glucosamine destabilized the deoxy-poly(AT) structure and changed its conformation from A form to X form. D-glucosamine also altered the conformation of deoxy-poly(GA)15 and deoxy-poly(CT)15 from A form to B form. Capillary electrophoresis and ultraviolet and fluorescence spectroscopy revealed that, of the various purines and pyrimidines, 2'-deoxyguanosine and guanine were most reactive with D-glucosamine. The nonenzymatic modification of nucleic acids warrants further investigation because this phenomenon may occur in vivo, altering DNA structure and/or function.
 ...
PMID:The effect of nonenzymatic glycation on the stability and conformation of two deoxyoligonucleotide duplexes: a spectroscopic analysis by circular dichroism. 1709 93

Diabetes is clearly associated with accelerated atherosclerosis development, but molecular mechanisms involved in diabetes-induced atherosclerosis remain to be clarified. The aim of this study was to identify cellular mechanisms involved in diabetes-induced macrophage foam cell formation, the hallmark of early atherogenesis. Mouse peritoneal macrophages (MPMs) isolated from Balb-C streptozotocin-induced diabetic mice, exhibited significantly higher total peroxides, lipid peroxides and paraoxonase 2 (PON2) activity by 290%, 61% and 55%, respectively, compared to non-diabetic mice. In vitro studies revealed that glucose-induced oxidative stress was obtained by D-glucose, but not by L-glucose and it involved activation of the NADPH oxidase complex, and up-regulation of the macrophage PON2. Next, MPMs isolated from Balb-C diabetic mice, compared to control Balb-C mice, demonstrated increased cholesterol content by 4.2-fold associated with increased cholesterol biosynthesis and increased uptake of oxidized LDL (Ox-LDL) by 5.9-fold and 31%, respectively. These effects on cellular cholesterol metabolism were associated with up-regulation of the scavenger receptors for Ox-LDL (CD-36 and SR-A), and of HMG-CoA reductase (cholesterol biosynthesis rate limiting enzyme). Finally, using pravastatin (inhibitor of HMG-CoA reductase) and the antioxidant Vitamin E, we have shown that D-glucose-induced macrophage oxidative stress is secondary to its stimulatory effect on macrophage cholesterol biosynthesis. In conclusion, macrophages from diabetic mice demonstrate increased oxidative stress associated with activation of NADPH oxidase and up-regulation of cellular PON2, as well as increased macrophages cholesterol uptake and biosynthesis (increased expression of CD-36 and HMG-CoA reductase). The above mechanisms in diabetic mice could be the result of the effect of high D-glucose on macrophages.
Atherosclerosis 2007 Dec
PMID:Macrophage NADPH oxidase activation, impaired cholesterol fluxes, and increased cholesterol biosynthesis in diabetic mice: a stimulatory role for D-glucose. 1725 48

To investigate the effects of 2,3,5,4'-tetrahydroxystilbene-2-O-beta-D-glucoside (THSG), a compound extracted from the root of Polygonum multiflorum Thunb, on lipoprotein (LDL and VLDL) oxidation, proliferation and nitric oxide (NO) content of coronary arterial smooth cells (CASMCs) induced by LDL, VLDL, ox-LDL and ox-VLDL. The oxidation level of lipoprotein was determined by thiobabituric acid (TBA) method and agarose gel electrophoresis. The proliferative degree was determined by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) method. The NO content was assayed by nitrate reductase method. (1)THSG (0.1 - 100 mumol L(- 1)) could dose-dependently prevent lipoprotein from oxidation induced by Cu(2 + ) and CASMCs. (2)THSG (0.1 - 100 micromol L(- 1)) inhibited porcine CASMCs proliferation elicited by LDL, VLDL, ox-LDL and ox-VLDL. (3)THSG (0.1 - 100 micromol L(- 1)) counterpoised the decrease of NO content in CASMCs evoked by LDL, VLDL, ox-LDL and ox-VLDL. As compared with control, it was found that the threshold concentration of THSG, which significantly exerted the actions mentioned above, were at the concentration of 1 micromol.L(- 1) (P < 0.01). In conclusion, THSG possesses the antagonistic effects on oxidation of lipoprotein, proliferation and decrease of NO content of CASMCs, which partially explain the mechanism of anti-atherosclerosis of Polygonum multiflorum Thunb.
 ...
PMID:Effect of 2,3,5,4'-tetrahydroxystilbene-2-O-beta-D-glucoside on lipoprotein oxidation and proliferation of coronary arterial smooth cells. 1770 57

1. In coronary artery disease, the typical atheromatous plaque consists of a lipid core containing various inflammatory cells and a fibrous cap composed mostly of extracellular matrix. Both matrix metalloproteinases (MMPs) and inflammation are involved in the initiation of atherosclerotic plaques and plaque instability. 2. 2,3,4 cent,5-Tetrahydroxystilbene-2-O-beta-D-glucoside (TSG) reduces the blood lipid content and prevents the atherosclerotic process, but the mechanism of action of TSG is unclear. The purpose of the present study was to test whether TSG can suppress MMP activation and inflammation in atherosclerotic rats. 3. Sixty male Sprague-Dawley rats were randomly divided into six groups. Atherosclerosis was induced by feeding rats a hyperlipidaemic diet; TSG (120, 60 or 30 mg/kg per day) was administered by oral gavage. After 12 weeks of treatment, rats were killed (ethyl carbamate 1200 mg/kg) and serum lipids, C-reactive protein (CRP), interleukin (IL)-6 and tumour necrosis factor (TNF)-alpha were measured. Haematoxylin-eosin (H&E) staining was used to examine histopathological changes in the aorta. The mRNA and protein expression of MMPs were assayed by reverse transcription-polymerase chain reaction, immunohistochemistry and western blotting. Simvastatin (2 mg/kg per day) was administered as a positive control, whereas the vehicle (0.9% NaCl) group served as the untreated control. 4. In the present study, TSG significantly and dose-dependently attenuated the hyperlipidaemic diet-induced alterations in serum lipid profile and increases in CRP, IL-6 and TNF-a levels. In addition, TSG normalized the structure of the aortic wall and suppressed the expression of MMP-2 and MMP-9 at both the mRNA and protein level in the rat aortic wall. 5. In summary, TSG suppresses the expression of MMP-2 and MMP-9 and inhibits inflammation in the diet-induced atherosclerotic rats.
 ...
PMID:2,3,4',5-Tetrahydroxystilbene-2-O-beta-D-glucoside suppresses matrix metalloproteinase expression and inflammation in atherosclerotic rats. 1797 30

Type 2 diabetes is associated with a two to fourfold increased risk of both coronary heart disease and stroke. Dysfunction of endothelial cells (EC) is known to promote abnormal vascular growth such as that in atherosclerosis and arteriosclerosis and has been postulated as an initial trigger of the progression of atherosclerosis in patients with diabetes mellitus, and hyperglycemia is an independent risk factor for the development of cardiovascular disease. We and others have previously demonstrated that high D-glucose induced apoptosis through activation of the bax-caspase proteases pathway in human EC and the potential contribution of hepatocyte growth factor, as an anti-apoptotic factor, to the pathogenesis of endothelial dysfunction. The anti-apoptotic action of HGF was due to bcl-2-upregulation and the phosphatidylinositol 3-kinase pathway, which is involved in Akt activation. Although it has been known for years that cardiovascular tissues can release a large amount ROS, including superoxide, hydrogen peroxide, and nitric oxide, the role of oxidative stress in atherogenesis has received increasing attention in recent years. Recent work strongly suggests that NADPH oxidase is a major source of superoxide in cardiovascular cells, and oxidative stress can be involved in the process of endothelial dysfunction. NADPH oxidase can be activated in hyperglycemia through the protein kinase C pathway. From the viewpoint of these molecular mechanisms, HMG-CoA reductase inhibitors (statins) might inhibit the high glucose-induced NADPH oxidase activation through inhibition of Rac activity and finally prevent the increase in ROS production in diabetes. A recent clinical trial suggested that statins prevent several vascular events in patients with type 2 diabetes without a high concentration of LDL-cholesterol. These pleiotropic effects of statins can be expected to improve endothelial dysfunction through nitric oxide production and/or an anti-oxidant effect in diabetic patients.
 ...
PMID:Endothelial dysfunction in hyperglycemia as a trigger of atherosclerosis. 1822 May 82

Studies have suggested that dietary flavonoids are helpful in the prevention of atherosclerosis and cardiovascular disease. Antioxidant activity should be noted as underlying mechanism of their health impact in the vascular system, as atherosclerosis is closely related to oxidative events such as oxidized LDL accumulation in the macrophages. Vegetables contain a variety of flavonoids, such as flavonols, flavones and anthocyanidins. We focused on quercetin (3,3',4',5,7- pentahydroxyflavone), a major flavonoid in onion, and its anti-atherosclerotic effect was examined from the aspect of the bioavailability and translocation to the target site. Although quercetin exists as its glucoside form in onion, it is metabolized into several glucuronides and/or sulfate conjugates with or without methylation during its intestinal absorption. We found that these metabolites circulating in the human blood stream were mostly localized in plasma albumin fraction, but not LDL fraction. Onion consumption failed to enhance the antioxidant activity of plasma fraction against LDL oxidation, indicating that the level of quercetin metabolites bound to albumin is insufficient to exert the antioxidative effect in vivo. In contrast, we discovered that quercetin metabolites accumulate in the aorta tissue and exerted their antioxidant activity, when rabbits were fed with quercetin glucoside and high cholesterol diet. Furthermore, quercetin metabolites were detected in human atherosclerotic aorta exclusively. These imply that quercetin metabolites are incorporated into the atherosclerotic region and act as complementary antioxidants, when oxidative stress is loaded in the vascular system. It is likely that plasma albumin is a carrier for translocation of quercetin metabolites to vascular target.
 ...
PMID:Vegetable flavonoids and cardiovascular disease. 1829 59

CD40-mediated inflammatory signaling is a potent activator of endothelial cells (ECs) and effective in triggering the pathogenesis of atherosclerosis, a chronic inflammatory disease. Anthocyanin is considered to exert potent cardiovascular-protective effect partially through its anti-inflammatory property, however, the precise mechanism is still unknown. Here we chose cultured human umbilical vein endothelial cells (HUVECs) to explore the influence of anthocyanin on CD40-mediated endothelial activation and apoptosis and the underlying mechanism. Stimulation of human primary HUVECs by CD40 with its physiological ligand CD40L not only augmented MMP-1, -9 secretion and promoted MMP-1, -9 activities, but also induced endothelial cell apoptosis and death. Treatment of ECs with anthocyanins cyanidin-3-O-beta-glucoside (Cy-3-g) and peonidin-3-O-beta-glucoside (Pn-3-g) prevents CD40-induced endothelial activation by inhibiting production of proinflammatory cytokines and matrix metalloproteinases (MMPs). In addition, exposure to anthocyanins inhibits CD40-induced endothelial apoptosis. Anthocyanins also decreased activation of JNK and p38 induced by CD40. Collectively, our findings suggested that the inhibition of JNK and p38 activation interrupts CD40 induced endothelial cell activation and apoptosis, which thereby may represent a mechanism that would explain the anti-inflammatory response of anthocyanin and its athero-protective function.
Atherosclerosis 2009 Jan
PMID:Anthocyanin attenuates CD40-mediated endothelial cell activation and apoptosis by inhibiting CD40-induced MAPK activation. 1849 29

2,3,4',5-Tetrahydroxystilbene 2- O-beta- D-glucoside (TSG), an active component extracted from Polygonum multiflorum, has been found to have an anti-atherosclerotic effect. The aim of this study was to investigate whether the TSG could prevent the development of atherosclerosis through influencing endothelial function in atherogenic-diet rats and to explore the possible mechanisms. Vascular endothelial dysfunction was assessed using isolated aortic ring preparation, transmission electron microscopy of the aorta, and levels of nitrate/nitrite (NOx) in serum and aorta. Endothelial nitric oxide (NO) synthase (eNOS) and inducible NO synthase (iNOS) mRNA and protein expression were also measured. After 12 weeks treatment, TSG improved acetylcholine-induced endothelium-dependent relaxation, prevented intimal remodeling, inhibited the decreased NOx content in serum and aorta in atherogenic-diet rats. Furthermore, the observed decreased eNOS mRNA and protein expression and increased iNOS mRNA and protein expression in atherogenic-diet rats were attenuated by TSG treatment. These results suggest that TSG could restore vascular endothelial function, which may be related to its ability to prevent changes of eNOS and iNOS expression, leading to preservation of NO bioactivity.
 ...
PMID:Effects of 2,3,4',5-tetrahydroxystilbene 2-O-beta-D-glucoside on vascular endothelial dysfunction in atherogenic-diet rats. 1935 Apr 77

Our aim was to quantify changes in the inflammatory and calcific components of atherosclerosis in the aortic wall using fluoro-18-2-fluoro-2-deoxy-D-glucose positron emission tomography (18)F-FDGPET and contrast enhanced computerized tomography (CECT) with increasing age. Twelve subjects, 8 men and 4 women aged from 21-80 years who had both (18)F-FDG-PET and CECT of the chest and abdomen were included in this study. Subjects were grouped into three according to age. (18)F-FDG uptake in four segments of the aorta was measured. Using CECT images, aortic segmental wall volumes were measured. Wall calcification volume in each aortic segment was also measured via adaptation of a coronary artery calcium-scoring program to the aorta. Calcification volumes were then subtracted from aortic wall volumes. Each net segmental aortic wall volume was then multiplied by the accompanying mean SUV of the segment to calculate global metabolic activity (GMA) for each aortic segment. Our results showed that in each aortic wall segment, mean SUV, wall volumes, wall calcification volumes, and GMA statistically significantly increased with age. In conclusion, (18)F-FDG uptake, wall volume, wall calcification volume, and GMA in the aorta increase with aging. The (18)F-FDG uptake represents the early inflammatory component of the atherosclerotic process, whereas calcification generally represents a later and irreversible stage of the disease. Measurement and combination of PET and CECT parameters to calculate GMA may allow for optimal morphologic and functional noninvasive quantitative assessment of global aortic atherosclerotic disease.
 ...
PMID:A pilot study of changes in (18)F-FDG uptake, calcification and global metabolic activity of the aorta with aging. 1967 64


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>