Showing papers on "Fatty streak published in 2011"

Lipoprotein associated phospholipase A 2 : role in atherosclerosis and utility as a biomarker for cardiovascular risk

Abstract: Atherosclerosis and its clinical manifestations are widely prevalent throughout the world. Atherogenesis is highly complex and modulated by numerous genetic and environmental risk factors. A large body of basic scientific and clinical research supports the conclusion that inflammation plays a significant role in atherogenesis along the entire continuum of its progression. Inflammation adversely impacts intravascular lipid handling and metabolism, resulting in the development of macrophage foam cell, fatty streak, and atheromatous plaque formation. Given the enormous human and economic cost of myocardial infarction, ischemic stroke, peripheral arterial disease and amputation, and premature death and disability, considerable effort is being committed to refining our ability to correctly identify patients at heightened risk for atherosclerotic vascular disease and acute cardiovascular events so that they can be treated earlier and more aggressively. Serum markers of inflammation have emerged as an important component of risk factor burden. Lipoprotein-associated phospholipase A2 (Lp-PLA2) potentiates intravascular inflammation and atherosclerosis. A variety of epidemiologic studies support the utility of Lp-PLA2 measurements for estimating and further refining cardiovascular disease risk. Drug therapies to inhibit Lp-PLA2 are in development and show considerable promise, including darapladib, a specific molecular inhibitor of the enzyme. In addition to substantially inhibiting Lp-PLA2 activity, darapladib reduces progression of the necrotic core volume of human coronary artery atheromatous plaque. The growing body of evidence points to an important role and utility for Lp-PLA2 testing in preventive and personalized clinical medicine.

Role of Heparanase on Hepatic Uptake of Intestinal Derived Lipoprotein and Fatty Streak Formation in Mice

Abstract: Background Heparanase modulates the level of heparan sulfate proteoglycans (HSPGs) which have an important role in multiple cellular processes. Recent studies indicate that HSPGs have an important function in hepatic lipoprotein handling and processes involving removal of lipoprotein particles. Principal Findings To determine the effects of decreased HSPGs chain length on lipoprotein metabolism and atherosclerosis, transgenic mice over-expressing the human heparanase gene were studied. Hepatic lipid uptake in hpa-Tg mice were evaluated by giving transgenic mice oral fat loads and labeled retinol. Sections of aorta from mice over-expressing heparanase (hpa-Tg) and controls (C57/BL6) fed an atherogenic diet were examined for evidence of atherosclerosis. Heparanase over-expression results in reduced hepatic clearance of postprandial lipoproteins and higher levels of fasting and postprandial serum triglycerides. Heparanase over-expression also induces formation of fatty streaks in the aorta. The mean lesion cross-sectional area in heparanase over-expressing mice was almost 6 times higher when compared to control mice (23,984 µm2±5,922 vs. 4,189 µm2±1,130, p<0.001). Conclusions Over-expression of heparanase demonstrates the importance of HSPGs for the uptake of intestinal derived lipoproteins and its role in the formation of fatty streaks.

The Interaction of Plasma Sialylated and Desialylated Lipoproteins with Collagen from the Intima and Media of Uninvolved and Atherosclerotic Human Aorta

Abstract: We have evaluated the binding of sialylated and desialylated lipoproteins to collagen isolated from the proteoglycan and musculoelastic layers of intima and media of uninvolved human aorta and atherosclerotic lesions. Comparing various collagen preparations from the uninvolved intima-media, the binding of sialylated apoB-containing lipoproteins was best to collagen from the intimal PG-rich layer. Binding of sialylated apoB-containing lipoproteins to collagen from this layer of fatty streak and fibroatheroma was 1.4- and 3.1-fold lower, respectively, in comparison with normal intima. Desialylated VLDL versus sialylated one exhibited a greater binding (1.4- to 3.0-fold) to all the collagen preparations examined. Desialylated IDL and LDL showed a higher binding than sialylated ones when collagen from the intimal layers of fibroatheroma was used. Binding of desialylated HDL to collagen from the intimal PG-rich layer of normal tissue, initial lesion, and fatty streak was 1.2- to 2.0-fold higher compared with sialylated HDL.

Reduces cholesterol induced atherosclerotic lesions in aorta artery in hypercholesterolemic rabbits

Abstract: Atherosclerosis is the leading cause of death in developed countries with many proved risk factors. Vinegar has been proved to have some medical uses and some potential protective effects on atherosclerosis. In this study, effects of vinegar on various risk factors of atherosclerosis and development of atherosclerosis in hypercholesterolemic rabbit have investigated. Rabbits were assigned to four groups and each group received one of experimental diets: normal diet, high cholesterol diet (1% cholesterol), 1% cholesterol supplemented with 5 ml vinegar and 1% cholesterol supplemented with 10 ml vinegar for 8 weeks. Blood samples were collected before and after 8 weeks of experimental diets for measurement of serum C-reactive protein (CRP), nitrite, nitrate, apolipoprotein A (ApoA 1) and apolipoprotein B (ApoB 100 ), total cholesterol (TC), fibrinogen and factor VII. At the end of study, fatty streak formation in aorta was determined in all groups. Using vinegar (5 and 10 ml) with hypercholesterolemic diet caused significant reduction in CRP, fibrinogen, factor VII, ApoB 100 , ApoB/ApoA ratio, TC levels, atherosclerotic lesions in aorta and increased nitrite and nitrate in comparison with hypercholesterolemic diet. Vinegar did not significantly change ApoA 1 level compared to high cholesterol diet. These results suggest that vinegar reduced atherosclerosis processes in high cholesterol diet fed animals. More studies are needed to find the exact mechanisms of action.

Pioglitazone modulates the balance of effector and regulatory T cells in apolipoprotein E deficient mice.

Abstract: Background and aims Pioglitazone (PIO) affects T cell-mediated immunity through actions of peroxisome proliferator activated receptor γ (PPARγ) Effector and regulatory T cells control the development of atherosclerosis, a chronic inflammatory disease affecting the arterial blood vessels The aim of this study was to examine whether PIO ameliorates atherosclerosis by altering the balance of effector and regulatory T cells Methods and results To explore the effect of PIO on early and advanced atherosclerosis, apolipoprotein E deficient (ApoE−/−) mice were fed western diet and received PIO (20 mg/kg/day) by gastric gavage at 6 or 14 weeks of age, respectively for 8 weeks Data showed PIO markedly inhibited early fatty streak formation Further, although the advanced fibrofatty plaque sizes were not significantly reduced, the numbers of smooth muscle cells within lesions were increased and higher collagen concentrations were produced In general, macrophage expression in lesions was decreased Additionally, the expression of Foxp3 + cells was increased in lesions and spleens in mice at all PIO treatment stages, whereas the CD4 + IFN-γ + /CD4 + IL-4 + cell ratios were reduced Conclusion PIO inhibited early atherosclerotic lesion formation and increased the stability of advanced atherosclerotic plaques in ApoE−/− mice, which was associated with altering the balance of effector and regulatory T cells

Ceruloplasmin and oxidized LDL colocalize in atherosclerotic lesions of hamster

Abstract: Epidemiological studies show that the risk for cardiovascular diseases increases with increasing levels of free-copper in plasma. It is known that intact ceruloplasmin (CP), the major protein transporter of copper in human plasma, oxidizes low density lipoproteins (LDL) in vitro. Our aim was to study the interaction between LDL and CP in vitro and in vivo, in an animal model of diet-induced atherosclerosis. In order to visualize the pathway of LDL into the arterial wall, human native LDL was labeled with fluorescent DiI and injected into male, Golden Syrian hyperlipemic hamsters. In vitro results demonstrated that slightly degraded CP has a significant oxidation potential against LDL at neutral pH. In vivo, after 24 hours circulation, LDL-DiI was taken up by the enlarged intima and fatty streaks of the arterial wall. Immunohistochemical localization of oxidized LDL and CP revealed their presence in the same areas of the arteries that take up LDL-DiI. Co-localization of LDL and CP in the enlarged intima of pro-atherosclerotic areas might explain the possible copper-induced oxidation process that might occur after native LDL is taken-up from the blood, transcytosed through the endothelium and accumulated in focalized deposits.

The effects of concurrent hydroalcoholic extract of Amaranthus caudatus L. and Hypericum perforatum L. of fatty streak formation in hypercholesterolemic animals

Abstract: Hypercholesterolemia, a high cholesterol diet and oxidative stress increase serum low density lipoprotein (LDL) levels resulting in increased risk for development of atherosclerosis. Antioxidants play an important role in inhibiting and scavenging radicals, thus providing protection to humans against contagious and degenerative diseases. The aim of this study was to assess the anti-fatty streak effects of concurrent hydroalcoholic extracts of Amaranthus caudatus L. (A. caudatus) and Hypericum perforatum L. (H. perforatum) as this were investigated in hypercholesterolemic rabbits and was compared with lovastatin. Rabbits were randomly divided into four groups which were fed with normal diet (control), high-cholesterol diet (hypercholesterolemic control group), high-cholesterol + concurrent hydroalcoholic extracts of A. caudatus (75 mg/kg daily) and H. perforatum (75 mg/kg daily) (treatment group), and high-cholesterol + lovastatin (10 mg/kg daily) (treatment group) for 60th days and then blood samples were obtained to measure plasma cholesterol, triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), apolipoproteinA (apoA), apolipoproteinB (apoB), malondialdehyde (MDA), C-reactive protein (CRP), Ox-LDL and AI aorta was also obtained for histological evaluation. The observation showed decrease in plasma cholesterol, TG, HDL, LDL, apoB, CRP, MDA, OX-LDL, AI and increased apoA and HDL between treatment groups and hypercholesterolemic control groups (P>0.05). The mean size of produced fatty streak also showed significant reduction in the treatment groupIII compared to the hypercholesterolemic group (P<0.05). This results showed that combination of hydroalcoholic extracts of A. caudatus and H. perforatum has anti-fatty streak effects in hypercholesterolemic rabbits. Key words: Atherosclerosis, Amaranthus, Hypericum.

Early Atherosclerotic Lesions in Childhood and Adolescence

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