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)

Oxygen free radicals (OFRs) have been implicated in the development of hypercholesterolemic atherosclerosis. Flax seed is the richest source of omega-3 fatty acid and lignans. omega-3 Fatty acid suppresses the production of interleukin-1 (IL-1), tumor necrosis factor (TNF) and leukotriene B4 (LTB4), and of OFRs by polymorphonuclear leukocytes (PMNLs) and monocytes. Lignans possess anti-platelet activating factor (PAF) activity and are antioxidant. PAF, IL-1, TNF and LTB4 are known to stimulate PMNLs to produce OFRs. Flaxseed would, therefore, reduce the levels of OFRs and hence would prevent the development of hypercholesterolemic atherosclerosis. The effects of dietary flax seed on a high cholesterol diet induced atherosclerosis, lipid profile and OFR-producing activity of PMNLs (PMNL-CL) were investigated in rabbits. The rabbits were divided into 4 groups: group I, control; group II, flax seed diet (7.5 g/kg daily, orally); group III, 1% cholesterol diet; and group IV, same as group III but received flax seed (7.5 g/kg daily, orally). Blood samples were collected before and after 4 and 8 weeks on their respective diets for biochemical measurements and aortae were removed at the end of 8 weeks for estimation of atherosclerotic changes. The high cholesterol diet increased the serum level of total cholesterol (TC) and PMNL-CL without altering the levels of serum triglycerides (TG). These changes were associated with a marked development of atherosclerosis in the aorta. Flax seed reduced the development of aortic atherosclerosis by 46% and reduced the PMNL-CL without significantly lowering the serum cholesterol. Flax seed in normocholesterolemic rabbits increased serum total cholesterol and decreased PMNL-CL without significantly affecting the serum TG. Modest dietary flax seed supplementation is effective in reducing hypercholesterolemic atherosclerosis markedly without lowering serum cholesterol. Its effectiveness against hypercholesterolemic atherosclerosis could be due to suppression of enhanced production of OFRs by PMNLs in hypercholesterolemia. Dietary flax seed supplementation could, therefore, prevent hypercholesterolemia-related heart attack and strokes.
Atherosclerosis 1997 Jul 11
PMID:Dietary flax seed in prevention of hypercholesterolemic atherosclerosis. 924 61

The effects of plasma proteins on controlling the activity of matrix metalloproteinases (MMPs, matrixins) have been the focus of numerous studies, although only a few have examined the influence of matrixins on plasma proteins. Recently, it has been shown that MMPs may play a role in the degradation of fibrin. We have now investigated the role of collagenase-2 (MMP-8), macrophage elastase (MMP-12), collagenase-3 (MMP-13), and membrane type 1-matrix metalloproteinase (MT1-MMP, MMP-14) in the degradation of fibrinogen and Factor XII of the plasma clotting system. Our data demonstrate that the catalytic domains of MMP-8, MMP-12, MMP-13, and MMP-14 can proteolytically process fibrinogen and, with the exception of MMP-8, also inactivate Factor XII (Hageman factor). We have identified the amino termini of the major protein fragments. Cleavage of fibrinogen occurred in all chains and resulted in significantly impaired clotting. Moreover, rapid proteolytic inactivation of Factor XII (Hageman factor) by MMP-12, MMP-13, and MMP-14 was noted. These results support the hypothesis of an impaired thrombolytic potential of MMP-degraded Factor XII in vivo. MMP-induced degradation of fibrinogen supports a plasmin-independent fibrinolysis mechanism. Consequently, degradation of these proteins may be important in inflammation, atherosclerosis, and angiogenesis, all of which are known to be influenced by MMP activity.
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PMID:Matrix metalloproteinases collagenase-2, macrophage elastase, collagenase-3, and membrane type 1-matrix metalloproteinase impair clotting by degradation of fibrinogen and factor XII. 1093 Mar 99

Secoisolariciresinol diglucoside (SDG), an antioxidant isolated from flaxseed, is metabolized to secoisolariciresinol (SECO), enterodiol (ED), and enterolactone (EL) in the body. The effectiveness of SDG in hypercholesterolemic atherosclerosis, diabetes, and endotoxic shock could be due to these metabolites. These metabolites may have antioxidant activity. However, the antioxidant activity of these metabolites is not known. The antioxidant activity of SECO, ED, and EL was investigated using chemiluminescence (CL) of zymosan-activated polymorphonuclear leukocytes (PMNLs) [PMNL-CL]. Other antioxidants (SDG and vitamin E) were also used for comparison. SDG, SECO, ED, EL, and vitamin E, each in the concentration of 0.5, 1.0, 2.5, 5.0 and 10.0 mg/ml, produced a concentration-dependent reduction in zymosan-activated PMNL-CL. SDG, SECO, ED, EL, and vitamin E, in the concentration of 2.5 mg/ml, produced a reduction of zymosan-activated PMNL-CL by 23.8%, 91.2%, 94.2%, 81.6% and 18.7%, respectively. Activated PMNLs produce reactive oxygen species and luminol-dependent CL reflects the amount of oxygen species generated from activated PMNLs. The reduction of PMNL-CL, therefore, reflects the antioxidant activity of the compounds studied. These results suggest that the metabolites of SDG have antioxidant activity. The antioxidant activity was highest with SECO and ED and lowest with vitamin E. The antioxidant potency of SECO, ED, EL, and SDG was 4.86, 5.02, 4.35, and 1.27 respectively, as compared to vitamin E. SECO, ED and EL are respectively 3.82, 3.95, and 3.43 more potent than SDG.
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PMID:Antioxidant Activity of Secoisolariciresinol Diglucoside-derived Metabolites, Secoisolariciresinol, Enterodiol, and Enterolactone. 1106 11

Cigarette smoking has been associated with an increase in the severity and prevalence of atherosclerosis in the abdominal aorta. To begin our investigation of this finding, we used an integrated approach combining gene expression profiling, protein analysis, cytokine measurements, and cytotoxicity determinations to examine molecular responses of cultured human aortic and coronary endothelial cells exposed to cigarette smoke condensate (CSC) and nicotine. Exposure of endothelial cells to CSC (30 and 60 microg/mL TPM) for 24 h resulted in minimal cytotoxicity, and the upregulation of genes involved in matrix degradation (MMP-1, MMP-8, and MMP-9), xenobiotic metabolism (HO-1 and CYP1A2), and downregulation of genes involved in cell cycle regulation (including TOP2A, CCNB1, CCNA, CDKN3). Exposure of cells to a high physiological concentration of nicotine resulted in few differentially expressed genes. Immunoblot analysis of proteins selected from genes shown to be differentially regulated by microarray analysis revealed similar responses. Finally, a number of inflammatory cytokines measured in culture media were elevated in response to CSC. Together, these results describe a complex proinflammatory response, possibly mediating the recruitment of leukocytes through cytokine signaling. Additionally, fibrous cap destabilization may be facilitated by matrix metalloproteinase upregulation.
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PMID:Matrix-degrading and pro-inflammatory changes in human vascular endothelial cells exposed to cigarette smoke condensate. 1450 Oct 29

Carotid atherosclerotic plaque remodelling and increased risk of symptomatic plaque rupture seem to be partially mediated by matrix metalloproteinases (MMPs). In this study, we have investigated whether different MMPs are related to carotid atherosclerosis or to recent ischaemic brain disease. Eighty-four consecutive patients undergoing carotid endarterectomy for symptomatic and asymptomatic disease were studied. Plaques were analysed by ultrasound and later by morphology. Plasma MMP-2, MMP-8 and MMP-9 levels were quantified by ELISA. MMP expression and activity in carotid plaques was analysed by Western blotting and in situ zymography. Results were analysed with respect to plaque stability, morphology, symptomatic disease, presence of vascular risk factors and plasma markers of acute inflammation as high sensitivity C-reactive protein (hsCRP), fibrinogen, D-dimer and white blood cell counts. Patients with hypoechogenic plaques on ultrasound had more plasma MMP-8 (p = 0.04) and increased MMP activity as assessed by in situ zymography. Asymptomatic patients with plaque progression had more active intraplaque MMP-8 than asymptomatic patients without plaque progression. Presence of recent intraplaque haemorrhage or past history of CAD was related to increased activity of MMPs as assessed by in situ zymography (p < 0.01, CI 95% 0.8-1.0). Plasma MMP-8 and MMP-9, but not MMP-2 levels, decrease with time after ischaemic stroke. Patients with hypertension had more intraplaque active MMP-9 than normotensive (p = 0.03, CI 95% 0.7-1.0). Hypoechogenic carotid plaques had increased MMP activity and asymptomatic patients with plaque progression show increase intraplaque MMP-8 levels.
Atherosclerosis 2006 Jul
PMID:Intraplaque MMP-8 levels are increased in asymptomatic patients with carotid plaque progression on ultrasound. 1625 88

Matrix metalloproteinases (MMPs) play a role in collagen breakdown, leading to plaque instability. High levels of MMPs mRNA and proteins, especially MMP-1, MMP-2, MMP-8, MMP-9, and MMP-13, were shown in human atherosclerotic plaques. However, among various MMPs, only MMP-1, MMP-8 and MMP-13, so-called interstitial collagenases, can initiate collagen breakdown. To elucidate whether MMP-1, MMP-8 and MMP-13 levels in blood were high in patients with unstable angina (UAP), we measured serum MMP-1 and plasma MMP-8 and MMP-13 levels in 45 patients with UAP, 175 with stable coronary artery disease (CAD), and 45 controls. Plasma C-reactive protein levels tended to be higher in patients with UAP than in those with stable CAD and controls (median 0.94 vs. 0.69 and 0.51mg/l). Regarding blood levels of MMPs, MMP-13 levels were above the lower detection limit in only one patient with UAP (2%), one with stable CAD (1%), and none in controls. MMP-1 levels did not differ among patients with UAP, stable CAD, and controls (median 4.8, 5.3, and 5.4ng/ml). Notably, MMP-8 levels were higher in patients with stable CAD than in controls (median 3.5ng/ml vs. 2.8ng/ml, P<0.005), however, MMP-8 levels in patients with UAP were much higher than those in stable CAD (3.9ng/ml vs. 3.5ng/ml, P<0.05). In multivariate analysis, MMP-8 level was an independent factor for UAP. Thus, plasma MMP-8 levels were found to be high in patients with UAP, suggesting that MMP-8 levels in UAP may reflect coronary plaque instability and that MMP-8 is a promising biomarker for UAP.
Atherosclerosis 2010 Mar
PMID:High plasma levels of matrix metalloproteinase-8 in patients with unstable angina. 1967 46

Currently, the characteristics of aneurysms arising in the distal middle cerebral artery (dMCA) are not well understood. Here, we report the case of a 56-year-old woman with a ruptured saccular aneurysm in the M2 segment of the middle cerebral artery (MCA). The patient presented with a disturbance of consciousness, and computed tomography revealed a subarachnoid hemorrhage that angiography disclosed as a result of a saccular-type aneurysmal dilatation in the M2 segment of the left MCA. We excluded infection, inflammation, trauma, and neoplasia as causes of the aneurysm. Pathologic examination confirmed a ruptured saccular aneurysm of the dMCA that was unrelated to a branching zone. The aneurysmal wall was composed primarily of alphaSMA-positive and calponin/desmin-negative spindle cells and lacked internal elastic lamina, which was completely disrupted at the neck of the aneurysm. There was a strong positive immunoreactivity for matrix metalloproteinases (MMPs) 1, 2, and 9 in the spindle cells of the aneurysmal wall. In contrast, tests for MMP-8 were negative. The parent artery showed thickening of both the intima and media, with preservation of the internal elastic lamina. Atherosclerosis was not detected in either the parent artery or aneurysm. These findings suggest that an overexpression of MMPs may contribute to the development of saccular aneurysms in regions of the arterial trunk unrelated to branching zones.
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PMID:Histopathologic characteristics of a saccular aneurysm arising in the non-branching segment of the distal middle cerebral artery. 1996 51

Matrix metalloproteinases (MMPs) are involved in the remodeling of the extracellular matrix (ECM) in the arterial wall during atherogenesis. Collagens are the most abundant proteins in the ECM. MMP-8 is expressed by cells associated with the development of the atherosclerotic plaque. It cleaves collagen type I three times more potently than two other interstitial collagenases MMP-1 and MMP-13. The aim of this study was to investigate whether plasma MMP-8 values are associated with occurrence of carotid plaque (CP) and possible correlations with clinical and biochemical parameters in carotid atherosclerosis (CA) patients. Total plasma MMP-8 levels were quantified by ELISA in 63 patients with ultrasonographic evidence of CP presence and 12 controls. Plasma MMP-8 values were significantly higher in patients with CA compared with controls (median 23.36 ng/ml vs. 13.02 ng/ml, P<0.001) but they did not differ significantly according to gender, smoking and hypertensive status, associated diseases, and use of statins. Statistically significant positive correlations were observed between MMP-8 plasma values and C reactive protein (r=0.41, P=0.001), urea (r=0.50, P<0.001), aspartate transaminase (r=0.48, P=0.001), and creatinine levels (r=0.38, P=0.006). These results suggest association of MMP-8 plasma levels with occurrence of CP and correlation with certain biochemical markers.
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PMID:Plasma levels of matrix metalloproteinase-8 in patients with carotid atherosclerosis. 2062 27

Matrix-degrading proteases capable of degrading components of the extracellular matrix may play an important role in development and progression of atherosclerotic lesions. In the present study, we used the Ldlr(-/-)Apob(100/100) mouse model, which has a plasma lipoprotein profile similar to that of humans with atherosclerosis, to study the expression of matrix metalloproteinases (MMPs) during early stages of atherosclerosis development. We analyzed the expression of 11 proteases and three protease inhibitors in 5- to 40-week-old Ldlr(-/-)Apob(100/100) mice. Expression and activity of MMP-2 and MMP-9 was increased in advanced atherosclerotic lesions followed by macrophage infiltration as shown by real-time PCR, gel-based and in situ zymography and immunohistochemistry. Expression of other investigated MMPs did not increase during disease progression. However, the mRNA expression of MMP-8 and MMP-13 was down-regulated, which could explain the relatively high amount of collagen observed in the vessels in this model. In conclusion, low proteolytic expression at early stages of atherogenesis and a limited repertoire of proteolytic enzymes were associated with the progression of atherosclerosis in Ldlr(-/-)Apob(100/100) mice. The study suggests that MMP-2 and MMP-9 are the main proteases involved in atherogenesis in this mouse model.
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PMID:MMP-2 and MMP-9 are prominent matrix metalloproteinases during atherosclerosis development in the Ldlr(-/-)Apob(100/100) mouse. 2156 73

Experimental and clinical evidence supports the concept that metalloproteinases (MMPs), beyond different physiologic functions, also play a role in the development and rupture of the atherosclerotic plaque. Interest in MMPs has been rapidly increasing during the last years, especially as they have been proposed as biomarkers of vulnerable plaques. Different components of the metabolic syndrome (MS) have been identified as possible stimulus for the synthesis and activity of MMPs, like pro-inflammatory and pro-oxidant state, hyperglycemia, hypertension and dyslipidemia. On the other hand, anti-inflammatory cytokines like adiponectin are inversely associated with MMPs. Among the several MMPs studied, collagenases (MMP-1 and MMP-8) and gelatinases (MMP-2 and MMP-9) are the most associated with MS. Our aim was to summarize and discuss the relation between different components of the MS on MMPs, as well as the effect of the cluster of the metabolic alterations itself. It also highlights the necessity of further studies, in both animals and humans, to elucidate the function of novel MMPs identified, as well as the role of the known enzymes in different steps of metabolic diseases. Understanding the mechanisms of MS impact on MMPs and vice versa is an interesting area of research that will positively enhance our understanding of the complexity of MS and atherosclerosis.
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PMID:Metalloproteinases in metabolic syndrome. 2170 52


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