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)

Accumulation of extracellular matrix, fibrosis, is regarded to be one of the major manifestations of atherosclerosis. Collagen type I is the predominant matrix component in human atherosclerotic plaques. In this work we have demonstrated procollagen type I expressing cells (PCI-cells) and studied their localization in grossly normal human aorta and atherosclerotic lesions: initial lesions, fatty streaks, fibrolipid lesions (fibrolipid plaque, fibroatheroma), fibrotic lesions (fibrous plaque). PCI-cells were revealed immunocytochemically using SPI.D8 monoclonal antibody against human procollagen type I. We failed to detect PCI-cells in the areas of grossly normal aorta and media underlying atherosclerotic lesions. Positively stained cells were shown in the areas of initial lesions, fatty streaks, fibrolipid and fibrous plaques. The largest amount of PCI-cells was revealed in fatty streaks. These cells were predominantly localized in the preluminal proteoglycan-rich intimal sublayer. Intimal cells in grossly normal regions formed a common cellular network contacting each other with their processes. The cellular network is found to be partly disintegrated in atherosclerotic lesions, which leads to the appearance of isolated cells. The share of isolated PCI-cells localized outside the intimal cellular network was higher in advanced lesions than in the areas of early atherosclerotic lesions. In initial lesions most of PCI-cells were identified as smooth muscle cells using antibodies to smooth muscle alpha-actin. In fatty streaks PCI-expressing smooth muscle cells were fewer in number. Much fewer cells double-stained with anti-alpha-actin and anti-PCI antibodies were found in fibrolipid and fibrous plaques. The proportion of these double stained cells was higher among total number of PCI-cells involved in the cellular network versus PCI-cells outside the network. The results of the study demonstrated that the most active de novo synthesis of interstitial collagen takes place in the regions of atherosclerotic lesions characterized by lipid deposition, which may lead to the further progression of atherosclerotic lesions.
Atherosclerosis 1997 Apr
PMID:Collagen-synthesizing cells in initial and advanced atherosclerotic lesions of human aorta. 912 57

Antiplatelet drugs have been shown to prevent a range of atherothrombotic events, including transient ischaemic attack (TIA) and ischaemic stroke. Clopidogrel and ticlopidine are adenosine diphosphate (ADP)-receptor antagonists that inhibit ADP-induced fibrinogen binding to platelets, a necessary step in the platelet aggregation process. The Antithrombotic Trialists' Collaboration recently published a major meta-analysis that assessed the effect of antiplatelet therapy in patients with various manifestations of atherosclerosis. In total, this analysis included 135,000 patients in comparisons of antiplatelet agents versus control and 77,000 patients in comparisons of different antiplatelet regimens. This meta-analysis found that overall, antiplatelet therapy reduces the combined odds of stroke, myocardial infarction (MI) or vascular death by 22%, and that antiplatelet agents reduce the odds of a non-fatal stroke by 25% over a wide range of patients with or without a history of cerebrovascular disease. In the CAPRIE trial of clopidogrel versus acetylsalicylic acid (ASA), there was a 10% odds reduction for stroke, MI or vascular death in favour of clopidogrel (p = 0.03). In a meta-analysis performed by the Cochrane Stroke Group, ADP-receptor antagonist therapy significantly reduced the odds of a serious vascular event (stroke, MI or vascular death) by 9% (2p = 0.01) and of any stroke by 12%. The safety/tolerability profile of clopidogrel was superior to that of ticlopidine, and at least as good as that of ASA. In CURE, a long-term benefit was observed with the use of clopidogrel on top of standard therapy (including ASA in all patients), with a 20% relative risk reduction for the primary endpoint of cardiovascular death, MI or stroke (p < 0.001) in patients with unstable angina and non-Q-wave MI. A consistent benefit was seen across all patient subgroups, including patients with a previous history of stroke. More recently, CREDO has demonstrated the incremental benefit of prolonged use of clopidogrel on top of ASA in patients undergoing elective PCI, with a 27% reduction in the combined risk of death, MI or stroke after 12 months of therapy (p = 0.02) and a 25% reduction in stroke over the same time period. The MATCH trial is currently being conducted to test the hypothesis that long-term administration of clopidogrel on top of ASA is superior to clopidogrel alone for the reduction of major ischaemic events in patients with recent TIA or ischaemic stroke who are at high risk of atherothrombotic recurrence. Further trials of clopidogrel on top of standard therapy (including ASA) are planned in neurology; these include SPS3, in patients with small subcortical strokes, and ATARI, in patients who have recently recovered from a TIA.
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PMID:Evidence with antiplatelet therapy and ADP-receptor antagonists. 1269 15

Platelets are the most abundant blood source of CD40L, a proinflammatory and prothrombotic costimulatory molecule implicated in atherosclerosis. Agonist stimulation results in the secretion of a soluble form of CD40L (sCD40L) and GP IIb/IIIa receptor inhibition blocks secretion of sCD40L in vitro. However, the effect of GP IIb/IIIa inhibition on sCD40L levels in humans is unknown. Plasma sCD40L and inflammatory markers were measured (t = 0, 0.5, 2, and 24 hr post-PCI) in a cohort of patients receiving abciximab (n = 15), eptifibatide (n = 15), or no GP IIb/IIIa inhibitor (n = 15). PCI in the absence of GP IIb/IIIa inhibitor was associated with a small but measurable rise in sCD40L and the platelet-derived chemokine RANTES. In contrast, eptifibatide significantly lowered baseline sCD40L (P = 0.018) and RANTES (P = 0.006) levels. This effect was not observed with abciximab. GP IIb/IIIa inhibition with eptifibatide lowers levels of sCD40L and RANTES post-stenting, possibly conferring anti-inflammatory as well as antithrombotic effects.
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PMID:GP IIb/IIIa inhibition with eptifibatide lowers levels of soluble CD40L and RANTES after percutaneous coronary intervention. 1475 9

Diabetes mellitus is a metabolic disease with explicit complications on coronary vascular system. The incidence of coronary disease is rising in type 1 as well as in type 2 diabetes mellitus, and it is caused by precipitating atherosclerosis. It is unquestionable that disorders of different metabolic pathways cause acute coronary syndrome, the same holding true for postinfarction complications. Strict blood glucose control (glucose value should be close to the physiologic values) is imperative not only in the prevention but also in the treatment of acute coronary syndrome and prevention of reinfarction. It is obvious that medicamentous and surgical treatment of coronary heart disease in diabetic patients can reduce morbidity and mortality. The treatment of acute coronary heart syndrome in diabetic patients is very similar to that in nondiabetic patients, however, it demands extra efforts to establish good metabolic control. Due to more than one narrowing of coronary arteries in diabetic patients, angioplasty is often less efficient and there is a need of specific evaluation by a cardio-cardio surgical team to choose the method of treatment: stent implantation or arterial bypass. The strategy of optimal revascularization for diabetic patients who have multivascular coronary heart disease is still controversial. Although data on early percutaneous or surgical revascularization show longterm benefit, the early studies were carried out before the extensive use of intracoronary stents and thrombocyte inhibitors GP IIb/IIa. A dilemma about this question showed up when excellent results of drug eluting intracoronary stents brought up credibility of compared studies. For best patient selection, it has been recommended that decision should be based more on coronary anatomy rather than the presence or absence of diabetes mellitus. Surgical revascularization (CAGB) should be considered in patients with diabetes mellitus who have stenosis of the left main coronary artery, significant diffuse stenosis involving each of epicardial vessels, and patients who have mild to significant left ventricular systolic dysfunction. Patients with a relatively focal nature of the disease and free from left main coronary artery or confluence of front left descendent artery could be considered for PCI (primary coronary intervention). When stents become widely available, patients would probably request PCI first instead of CABG. It is very important to remember that irrespective of PCI or CABG being preferred in diabetic patients, the role of drug therapy is enormous. Due to the diabetic patient susceptibility to fast progression of the disease and plaque rupture, drug therapy is indispensable in this population, e.g., aspirin, clopidogrel, 3-hydroxy-3-methylglytaryl-coenzyme A (HMGCoA) inhibitor reductase and ACE-inhibitor.
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PMID:[Acute coronary syndrome in diabetes]. 1520 3

Ischemic heart diseases continue to be leading causes of death throughout the world. Blood platelets play a pivotal role not only in haemostasis but also in the pathogenesis of thrombosis and atherosclerosis, platelet aggregation being an essential step in the formation of either an effective haemostatic plug or an intravascular thrombus. The benefits of various antiplatelet therapies ranging from aspirin, ticlopidine, Clopidogrel, and intravenous platelet GPIIb/IIIa antagonists in various thromboembolic disorders are well documented. The studies of CAPRIE, CURE, PCI-CURE and MATCH have shown that the clopidogrel has a highly advantageous preventive effect in the ischaemic vascular diseases, that is why clopidogrel be highly recommended in the stroke prevention.
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PMID:[Clopidogrel in the prevention of stroke]. 1571 89

Prompted by a case where a patient (with no risk factors, and single vessel disease) developed angina pectoris after previous blunt chest trauma, we searched Medline for blunt chest trauma and myocardial ischaemia. We found 77 cases describing AMI after blunt chest trauma, but only one reporting angina pectoris. We focused on the age and sex distribution, type of trauma, the angiography findings and the time interval between the trauma and the angiography. The age distribution was atypical, compared to AMI in general; 82% of the patients with AMI after blunt chest trauma were less than 45 years old, and only 2.5% more than 60 years old. The most common trauma was a road traffic accident, and the LAD was the vessel most often affected. Angiography revealed 12 cases with completely normal vessels, which might be due to spasm or recanalisation; 31 cases showed occlusion but no atherosclerosis, which strongly suggested a causal relation between the trauma and subsequent occlusion. AMI should therefore be considered in patients suffering from chest pain after blunt chest trauma. Because traumatic AMI might often be the result of an intimal tear or dissection, thrombolytic therapy might worsen the situation and acute PCI must be considered preferable. It seems likely that lesser damage could lead to longer-term stenosis we suspect that this sequence is grossly under-reported. This could have medico-legal implications.
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PMID:Prior blunt chest trauma may be a cause of single vessel coronary disease; hypothesis and review. 1596 88

Pharmacological therapy for acute coronary syndrome (ACS) is divided into the treatment for myocardial ischemia and that for coronary thrombosis. Immediate nitrates(sublingual tablets and sprays) are used to alleviate attacks and patients not responding them are treated by intravenously in 24 hours. The initial treatment for non-ST-segment elevation myocardial infarction(NSTEMI) with the administration of nitrates and beta blocker is judged as Class I (evidence level B) by ACC/AHA classification. Administering beta blocker in patients with ACS has reduced the progression to myocardial infarction by 13%. Ca antagonist is administered in patients for whom nitrates and/or beta blocker are contraindicated or in whom myocardial ischemia persists or frequently relapses in spite of the treatment with an adequate dose of the drugs. Since recent studies have suggested that ACS may not result from a local vascular stenosis, but from coronary inflammation, treating the local vascular lesion alone with PCI is not enough. Rather, pharmacological therapy is important to reduce overall patient risk, thereby suppressing the progress of atherosclerosis.
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PMID:[Anti-anginal medication in management of acute coronary syndrome]. 1661 94

A residual platelet reactivity (RPR) on antiplatelet therapy in patients with ischemic heart disease (IHD) has been reported to be associated with adverse clinical events by some Authors. However, scarce data are present on the clinical parameters associated with this phenomenon. No study, at our knowledge, was designed with the specific aim to examine the relationship between clinical characteristics and RPR. We sought to evaluate the clinical and laboratory characteristics associated with RPR in patients with IHD undergoing coronary revascularization on dual (aspirin plus clopidogrel) antiplatelet therapy. We included in the study 868 patients undergoing a coronary angiography: 386 with acute coronary syndromes undergoing a primary coronary revascularization and 482 IHD patients scheduled to undergo an elective coronary angiography. We measured platelet function by both platelet aggregation with two agonists [0.5 mg/mL arachidonic acid (AA); 2 and 10 microM adenosine 5'-diphosphate (ADP)] and a point-of-care assay (PFA-100) on venous blood samples collected within 24 h from the end of the procedure. In patients with acute coronary syndromes and elective PCI diabetes is independently associated with RPR [group A: OR=2.9 (1.5-5.7) by 10 microM ADP, OR=5.3 (1.1-27.8) by PFA-100; group B: OR=4.0 (1.6-10.0) by 10 microM ADP]; reduced left ventricular systolic function [OR=3.7 (2.2-6.5) by AA-PA, OR=2.7 (1.6-4.6) by PFA-100], chronic use of aspirin [OR=0.2 (0.1-0.4) by AA-PA, OR=0.3 (0.2-0.5) by PFA-100] and loading dose of clopidogrel [OR=0.2 (0.06-0.5) by 10 microM ADP] were independent variables significantly associated with RPR in patients undergoing elective PCI. In addition, inflammatory status was found to be significantly associated with RPR in both groups of patients. These results provide indications for the selection of patients for whom the evaluation of platelet reactivity could be useful.
Atherosclerosis 2007 Nov
PMID:Residual platelet reactivity is associated with clinical and laboratory characteristics in patients with ischemic heart disease undergoing PCI on dual antiplatelet therapy. 1755 59

Inflammation in the injured vessel wall plays an essential role in the mechanism of restenosis. Pentraxin3 (PTX3) is synthesized at the inflammatory site in response to primary inflammatory stimuli. To establish the clinical significance of plasma PTX3 levels in the pathophysiology of inflammation in the injured vessels, we serially measured the levels in 20 patients undergoing elective coronary stenting. Plasma PTX3 levels increased 15 min after coronary stenting, and reached a maximum at 24h in the coronary sinus (P<0.001 versus baseline) and peripheral blood (P<0.001 versus baseline). The transcardiac gradient of PTX3 at 15 min after PCI was higher in patients with than those without restenosis (0.40+/-0.64 versus -0.19+/-0.33 ng/ml, P=0.02). Furthermore, the increase in PTX3 at 24h was positively correlated with the increase in activated Mac-1 on the surface of neutrophils at 48 h (r=0.48, p<0.05) in the coronary sinus. Stepwise multiple regression analysis demonstrated that the relative increase in PTX3 at 24h was the most powerful predictor of late lumen loss (r=0.547, P=0.007). Coronary stenting enhanced circulating PTX3 levels in association with an inflammatory response. PTX3 may be a useful marker for evaluation of inflammatory reaction and neointimal thickening after vascular injury.
Atherosclerosis 2008 Mar
PMID:Pentraxin3 is a novel marker for stent-induced inflammation and neointimal thickening. 1764 Jun 48

Thrombin is a multifunctional serine protease generated at the site of vascular injury that transforms fibrinogen into fibrin, activates blood platelets and elicits multiple effects on a variety of cell types including endothelial cells, vascular smooth muscle cells (VSMC), monocytes, T lymphocytes and fibroblasts. Cellular effects of thrombin are mediated by protease-activated receptors (PARs), members of the G protein-coupled receptors that carry their own ligand which remains cryptic until unmasked by proteolytic cleavage. Thrombin signalling in platelets contributes to haemostasis and thrombosis. In normal arteries PARs are mainly expressed in endothelial cells, while their expression in VSMC is limited. Endothelial PARs participate in the regulation of vascular tone, vascular permeability and endothelial secretory activity while in VSMC they mediate contraction, migration, proliferation, hypertrophy and production of extracellular matrix. PARs contribute to the pro-inflammatory phenotype observed in endothelial dysfunction and their up-regulation in VSMC seems to be a key element in the pathogenesis of atherosclerosis and restenosis. In the last years a myriad of studies have emphasized the critical role of PAR signalling in thrombin mediated effects in haemostasis, inflammation, cancer and embryonic development. Lately, PARs have become a therapeutic target to inhibit platelet aggregation and thrombosis. Early data from a clinical trial (TRA-PCI) to evaluate safety and efficacy of a potent new oral thrombin receptor antagonist (TRA) have promisingly indicated that overall TRA treatment reduces adverse event rates without an increase in bleeding risk. In this paper we review cellular responses triggered by thrombin and their implication in vascular pathophysiology.
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PMID:Thrombin and protease-activated receptors (PARs) in atherothrombosis. 1827 79


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