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)

The plasma CRP concentration has consistently been shown to be associated with the risk of future coronary heart disease (CHD) and recent studies have suggested that CRP has a pathogenic role in CHD. Family studies and genotype-phenotype association studies of known polymorphisms in the intron, second exon and 3'-untranslated region (UTR) have suggested that plasma CRP concentrations are under genetic control. However, no functional polymorphisms have so far been reported in the promoter region of the CRP gene. Screening of 1600 base pair (bp) of the promoter region of the CRP gene, using denaturing high performance liquid chromatography, revealed two novel common single nucleotide polymorphisms (SNPs). One of them, a three allelic SNP located at position -286 from the transcription start, was strongly associated with the plasma CRP concentration, predominantly in patients with CHD. No difference in allele frequency was seen between middle-aged post-infarction patients and population-based controls. The prognostic role and therapeutic implications in CHD and the functionality of this polymorphism remain to be determined.
Atherosclerosis 2005 Jan
PMID:A novel common single nucleotide polymorphism in the promoter region of the C-reactive protein gene associated with the plasma concentration of C-reactive protein. 1558 18

Orlistat lowers lipids and improves insulin sensitivity, but its effect on other metabolic syndrome related parameters is not known. To assess its influence on adiponectin, high sensitive C-reactive protein (hs-CRP) and other metabolic syndrome related parameters, this study enrolled 106 participants in a weight-reduction program and categorized them into a group of 51 who had been treated with orlistat 360 mg/day for one year and a group of 55 age and sex and body mass index (BMI) matched controls. The orlistat group had greater changes in BMI, % body fat (% BF), waist circumference, and insulin resistance, hs-CRP, leptin and adiponectin levels after one year on the program than the controls. After adjusting for % BF and waist circumference, change of serum leptin and adiponectin levels remained significantly different. It was found that orlistat could effectively manage obesity related co-morbidities, especially insulin resistance and atherosclerosis risk. It decreases leptin and increases adiponectin independent of % BF and waist circumference. Therefore, orlistat appears to have anti-diabetic and anti-atherogenic properties and may help prevent metabolic syndrome in the overweight people.
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PMID:Orlistat for obesity: benefits beyond weight loss. 1562 Apr 37

Cerebrovascular risk represents a progressive and evolving concept owing to the particular distribution of risk factors in patients with ischemic stroke and in light of the newest stroke subtype classifications that account for pathophysiological, instrumental, and clinical criteria. Age represents the strongest nonmodifiable risk factor associated with ischemic stroke, while hypertension constitutes the most important modifiable cerebrovascular risk factor, confirmed by a host of epidemiological data and by more recent intervention trials of primary (HOT, Syst-Eur, LIFE) and secondary (PROGRESS) prevention of stroke in hypertensive patients. To be sure, a curious relationship exists between stroke and diabetes. Although the Framingham Study, The Honolulu Heart Program, and a series of Finnish studies reported a linear relationship between improved glucose metabolism and cerebral ischemia, the clinical and prognostic profile of diabetic patients with ischemic stroke remains to be fully understood. Our group, on the basis of TOAST classification--a diagnostic classification of ischemic stroke developed in 1993 that distinguishes five different clinical subtypes of ischemic stroke: large-artery atherosclerosis (LAAS), cardioembolic infarct (CEI), lacunar infarct (LAC), stroke of other determined origin (ODE), and stroke of undetermined origin (UDE), and now extensively used in clinical and scientific context--analysed the prevalence of cerebrovascular risk factors and the distribution of TOAST subtypes in more 300 patients with acute ischemic stroke in two consecutives studies that reported the significant association between diabetes and the lacunar subtype and a better clinical outcome for diabetic patients, most likely related to the higher prevalence of the lacunar subtype. Well-confirmed are the roles of cigarette smoking, atrial fibrillation, and asymptomatic carotid stenosis as cerebrovascular risk factors. Particularly interesting seems to be the function of inflammation markers (CRP, TNF-alpha, IL-1 beta, ISPs) as potential risk factors. Still elusive remains the association between cholesterol serum levels and stroke, on the basis of the epidemiological data regarding this causative relationship, confirmed only by the results of intervention trials (4S, LIPID, CARE, HPS, ASCOT). Ultimately, cerebrovascular risk appears peculiar owing to the unique relationship between some modifiable risk factors (mainly diabetes and cholesterol) and the possible preferential association with stroke subtypes and specific cerebrovascular risks.
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PMID:Cerebrovascular risk factors and clinical classification of strokes. 1563 Jun 37

One of the most important questions in vasculitis research is not why inflammation of blood vessels occurs but why it persists, often in a site-specific manner. In this review we illustrate how stromal cells, such as fibroblasts and pericytes, might play an important role in regulating the site at which vasculitis occurs. Smooth muscle cells and fibroblasts directly influence the behaviour of overlying vascular cells, amplifying the response of the endothelium to proinflammatory agents such as TNF-alpha and allowing enhanced and inappropriate leucocyte recruitment. An abnormal local vascular stromal environment can therefore influence local endothelial function and drive the persistence of local vascular inflammation. However, such local vascular inflammation can have distant effects on the systemic vascular system, leading to widespread endothelial cell dysfunction. Vascular endothelial dysfunction is common in a range of immune-mediated inflammatory diseases, is seen in multiple vascular beds, and is reversible following the induction of disease remission. The mechanisms that drive such systemic vascular endothelial dysfunction are unclear but factors such as TNF-alpha and CRP may play a role. Persistence of such widespread endothelial dysfunction in systemic vasculitis appears to have long-term consequences, leading to the acceleration of atherosclerosis and premature ischaemic heart disease. It may also underlie the accelerated atherosclerosis seen in other immune-mediated rheumatic diseases, such as rheumatoid arthritis.
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PMID:Endothelial cells, fibroblasts and vasculitis. 1564 88

Chronic inflammatory stimulus seems to contribute to atherosclerotic process. Several studies have established a relationship between infective agents as Chlamydia pneumoniae, herpes virus and cytomegalovirus and atherosclerotic lesions. Aim of this study was to investigate the effects of influenza infective state on endothelial function of healthy young subjects, expressed as brachial flow-mediated vasodilation (FMV) and soluble form of intercellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1). In 10 male subjects (mean age 35+/-14 years) exhibiting influenza symptoms for 3 days, we determined total cholesterol, high-density lipoproteins (HDL), low-density lipoproteins (LDL), triglycerides, sVCAM-1, sICAM-1 and brachial FMV. All subjects had an antibody pattern characteristic of influenza A or B virus infection. After 3 months brachial FMV was significantly increased (8.6+/-2.3% versus 11.5+/-3.2%; p<0.001), while HDL (46+/-10 mg/dL versus 49+/-9 mg/dL; p<0.05), sICAM-1 and sVCAM-1 were reduced (respectively: 488+/-105 ng/mL versus 340+/-127 ng/mL; p<0.001, 1710+/-80 ng/mL versus 1216+/-63 ng/mL; p<0.001). Univariate analysis showed a positive correlation between changes in CRP and sICAM-1 levels (r=0.95, p<0.001), a negative one between changes in sICAM-1 and brachial FMV (r=-0.65, p<0.05) and between CRP and brachial FMV (r=-0.64, p<0.05). This small study suggested that inflammatory state determined by viral agents may transitorily alter endothelial function in healthy subjects.
Atherosclerosis 2005 Feb
PMID:Acute inflammatory state during influenza infection and endothelial function. 1569 44

The objective of this study was to determine the lipoprotein profile of limited cutaneous systemic sclerosis (LcSSc). Fasting lipids were determined in 24 female patients and 24 healthy age-matched and sex-matched controls. Exclusion criteria were conditions that induce an altered lipid profile. Lipoprotein levels of risk were determined in accordance with the National Cholesterol Education Program (NCEP). Significantly lower levels of high-density lipoprotein (HDL) cholesterol (47.6+/-12.4 mg dL(-1) vs. 58.2+/-12.3 mg dL(-1); P=0.003) and total cholesterol (197.0+/-40.7 mg dL(-1) vs. 222.0+/-34.0 mg dL(-1); P=0.02) were observed in LcSSc patients than in controls. The presence of anti-centromere antibodies (ACA) was also associated with lower HDL levels (45.0+/-12.1 mg dL(-1)) compared to ACA-negative patients and controls (50.2+/-12.6 and 58.2+/-12.3 mg dL(-1), respectively, P=0.01). The only clinical variable associated with low HDL levels was pulmonary hypertension (PH) (33.6+/-2.3 mg dL(-1) vs. 49.6+/-11.9 mg dL(-1), P=0.01). No significant correlation was observed among HDL levels and ESR (r=-0.313; P=0.14), CRP (r=-0.296; P=0.16), or BMI (r=-0.263; P=0.21). Remarkably, a higher percentage of risk HDL levels was identified in LcSSc patients (41.6%) than in healthy controls (8.3%) (P=0.02). Our data suggest that LcSSc patients, particularly those who are ACA positive, have an adverse lipid profile characterized by low HDL levels, a known independent risk for CAD in women. The relevance of this finding for the development of atherosclerosis in this disease must be confirmed by epidemiological studies.
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PMID:Lipoprotein profile in limited systemic sclerosis. 1628 68

Recent data have indicated that CRP (C-reactive protein) plays a role in atherosclerosis, in addition to being a marker for inflammatory diseases. IL-8 (interleukin-8), a CXC chemokine, is present in human coronary atheroma and promotes monocyte-endothelial cell adhesion. In the present study, we examined the effect of pitavastatin (NK-104), a synthetic statin (3-hydroxy-3-methylglutaryl CoA reductase inhibitor), on IL-8 production induced by CRP in human AoEC (aortic endothelial cells). We also investigated whether CRP can induce IL-8 production and if the activation of signalling pathways are functionally related. The concentrations of IL-8 in the media after stimulation with CRP were measured by ELISA, and the expression of IL-8 mRNA was assessed by Northern blot. The phosphorylation of MAPKs (mitogen-activated protein kinases) was determined by Western blot. The production of IL-8 induced by CRP (10 microg/ml) was enhanced significantly and was inhibited by pitavastatin. The expression of IL-8 mRNA was increased in a dose-dependent manner after stimulation with CRP (1-100 microg/ml), whereas expression of IL-8 mRNA induced by CRP (50 microg/ml) was significantly diminished by 5 microM pitavastatin. Furthermore, specific MAPK inhibitors (PD98059, SB203580 and SP600125) inhibited the expression of IL-8 mRNA induced by CRP (50 microg/ml). The phosphorylation of all three MAPKs [ERK (extracellular-signal-regulated kinase), p38 MAPK and JNK (c-Jun N-terminal kinase)] induced by CRP (10 microg/ml) was also significantly inhibited by pitavastatin. Our results suggest that CRP may play a role in atherosclerosis via IL-8 production and pitavastatin may prevent the progression of atherosclerosis not only by lowering plasma low-density lipoprotein cholesterol levels, but also by suppressing IL-8 production in endothelial cells through the inhibition of MAPK (ERK, p38 MAPK and JNK) pathways.
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PMID:Inhibitory effect of pitavastatin (NK-104) on the C-reactive-protein-induced interleukin-8 production in human aortic endothelial cells. 1570 Oct 58

Our previous study demonstrated that plasma concentration of high-sensitivity C-reactive protein (hs-CRP) is a marker of carotid atherosclerosis activity. In this study, we investigated whether plasma levels of soluble cell adhesion molecules have potential value to predict atherosclerosis progression. The study included 192 outpatients 40-82 years of age who were treated for traditional risk factor for cardiovascular disease. Patients underwent repeated ultrasonographic evaluation for 53+/-11 months. Severity of atherosclerosis was evaluated by the maximal intimal-medial thickness (max-IMT), plaque number (PN) and plaque score (PS, the sum of all plaque thicknesses). Blood samples were collected for measurement of hs-CRP, soluble intercellular adhesion molecule (sICAM-1) and sP-selectin at the time of baseline examination. The development of atherosclerosis was estimated by the formula: Deltavalue/year=(last value-baseline value)/number of follow-up years. Multivariate linear regression analysis revealed that sICAM-1 was associated with DeltaIMT/year and DeltaPS/year, which was not the case for sP-selectin. sICAM-1 was closely associated with DeltaIMT/year especially in patients with apparent atheromatous plaque. Our results suggested that levels of sICAM-1 might have predictive value of progression of carotid atherosclerosis independently of traditional risk factors and hs-CRP.
Atherosclerosis 2005 Mar
PMID:Associations of soluble intercellular adhesion molecule-1 with carotid atherosclerosis progression. 1572 Oct 22

C-reactive protein can be viewed as a basic marker of activity of the inflammatory response, which modulates the development and the progression of atherosclerosis including its life-threatening complications. At the same time, C-reactive protein represents an active partaker or mediator of this same inflammatory reaction. However, at the very beginning of atherosclerotic disease, C-reactive protein exerts a clear-cut antiatherogenic activity. The two aspects of CRP's function, i.e. both the pro-inflammatory and the anti-inflammatory one, respectively, stem from CRP's extent of co-operation with the complement system. From the evolutional point of view, the anti-inflammatory activity of CRP is the primary one, in that it sets stage for the host to remove foreign particles and to accelerate wound healing. The influence of well-known atherogenic risk factors converts the originally beneficial influence of CRP into pro-inflammatory and pro-atherogenic effects. This review article presents new conclusions from the "Mainz hypothesis". It shows that the primary protective action of CRP resides in its regulatory influence on the extent of activation of the complement system after the latter has been triggered by enzymatically remodeled low-density lipoproteins. In further course of atherosclerotic disease, C-reactive protein exhibits a full-blown proinflammatory activity. It can result in the progression of the primary morphologic lesions up to the development of sudden vascular events.
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PMID:[C-reactive protein in the pathogenesis of atherosclerosis: advantage and pitfalls of the "Mainz hypothesis"]. 1578 78

CRP (C-reactive protein) has not only emerged as a useful biomarker for cardiovascular disease, but also as a mediator of atherosclerosis. CRP directly activates vascular endothelial cells, amplifying the inflammatory response underlying atherogenesis. The expression of IL (interleukin)-8 appears to serve as one of the downstream effects of CRP. Kibayashi and co-workers in this issue of Clinical Science confirm that CRP induces IL-8 production in human aortic endothelial cells in vitro, via the activation of MAPKs (mitogen-activated protein kinases), an effect that can be inhibited by pitavastatin.
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PMID:C-reactive protein and statins: IL-8 as a molecular link? 1579 14


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