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)

Coronary syndromes are induced by atherosclerosis which results from lipid deposit as well as inflammatory cells in vascular walls triggered by oxidative modification of LDL cholesterol. Treatment with antioxidant vitamins (vitamin C and E) has no evident effect on coronary events whereas aspirin and statins treatments result in a 25 to 30% reduced rate of fatal and non fatal myocardial infarction in primary and in secondary prevention trials. Both drugs are highly recommended in secondary prevention. In primary prevention they are useful and cost effective if the estimated risk of coronary event is 1.5% per year or higher. They are not cost-effective if this risk is 0.6% per year or less. With aspirin there is a 1.5 fold increase of hemorrhagic stroke and a 2 fold increase of gastrointestinal hemorrhage. Aspirin is less efficient in younger patients (< 50 years of age), in those with high blood pressure (> 145 mmHg) and those with low serum hsCRP (< 1 mg/l.). Statins are well tolerated and they could reduce not only C-V and global mortality but also the risk of stroke and of macular degeneration. They could also delay the occurrence of diabetes and kidney failure. Folate administration can lower elevated serum homocysteine level, which is a risk factor for C-V and Alzheimer's disease. However the clinical benefit resulting from folate treatment must still be demonstrated.
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PMID:[Prevention of cardiovascular and degenerative diseases: I. Aspirin, statins, or vitamins?]. 1509 4

Atherosclerosis and its complications such as stroke, myocardial infraction and peripheral vascular disease, remain the major causes of morbidity and mortality in the world. Studies have showed that chemokines and adhesion molecules are involved in causing atherosclerosis by promoting directed migration of inflammatory cells. Monocyte chemoattractant protein-1 (MCP-1) is one of the key factors critical for the initiating and developing of atherosclerotic lesions. IL-8, a CXC chemokine, stimulates neutrophil chemotaxis. Aspirin is the most common drug used to prevent the complications of atherosclerosis such as stroke and coronary heart disease. In this study, we found that aspirin inhibited TNF-alpha (10 ng/ml)-induced MCP-1 and IL-8 expression at the RNA and protein levels in human umbilical vein endothelial cells (HUVECs), monocyte adhesion and transmigration, and that its inhibitory effects were not due to decreased HUVEC viability as assessed by MTT test. Aspirin at the dose as low as 10 microg/ml significantly inhibited the release of TNF-stimulated MCP-1 by 29.1% (P = 0.008) and IL-8 by 26.9% (P = 0.0146) as compared to TNF-stimulated release. Antibodies pretreatment were likely to decrease the production of MCP-1 (P < 0.0001) and IL-8 (P < 0.0001). Furthermore, aspirin (10 microg/ml) inhibited U937 cell adhesion by a 13.4% (P = 0.0119) inhibition as compared to TNF-stimulated alone. Finally, at higher concentration, aspirin also inhibited U937 migration to HUVEC by 89.1% (P = 0.0475) as compared to TNF-stimulated alone. These results in our study suggest that aspirin inhibits TNF-alpha stimulated MCP-1 and IL-8 release in HUVECs, for its additional therapeutic effects of aspirin in causing atherosclerosis.
Atherosclerosis 2004 Jun
PMID:Aspirin inhibits monocyte chemoattractant protein-1 and interleukin-8 expression in TNF-alpha stimulated human umbilical vein endothelial cells. 1513 50

Aspirin has potent antiinflammatory properties and attenuates atherosclerosis in apolipoprotein-E-deficient mice fed a high-fat, high-cholesterol diet. In an attempt to clarify the contradictory results obtained with normal chow, we studied the effect of aspirin for a prolonged period of time. The mice were fed a commercial chow until the experiment began at 8 weeks of age. Blood samples were then obtained and several mice (n=8) were sacrificed. The diet of the remaining 48 animals was supplemented with 200 g/kg palm fat and 1 g/kg cholesterol. They were then randomly divided into 2 groups, one of which received 0.5 mg/day of aspirin. The aspirin had a time-dependent effect. First, the extent of lesion decreased; then the effect was neutral; and, finally, after longer periods of being fed the atherogenic diet and receiving aspirin, the extent of the lesion increased. The transitory effect of aspirin should be elucidated in the absence of high dietary lipids.
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PMID:Aspirin attenuates the initiation but not the progression of atherosclerosis in apolipoprotein E-deficient mice fed a high-fat, high-cholesterol diet. 1524 71

Peripheral arterial disease (PAD) is not an uncommon but a commonly neglected condition by many medical practitioners. Its prevalence steadily increases with age. In Germany almost one fifth of the patients aged > 65 years suffer from it. With increasing life expectancy the prevalence of PAD seems to be on the increase. PAD is a manifestation of diffuse and severe atherosclerosis. A very strong association exists between PAD and other atherosclerotic disorders such as coronary artery disease (CAD) and cerebrovascular disease (CVD). PAD is an independent predictor of high mortality in patients with CAD. Smoking, diabetes mellitus and advancing age are the cardinal risk factors. A relatively small number of PAD patients lose limbs by amputation. Most patients with PAD die of either heart attacks or strokes and they die of the former conditions far earlier than controls. Numerous authors have reported activation of the coagulatory system in PAD, possibly because of the diffuse pattern of the disease. Platelet hyperactivity in PAD may play a role in the process that leads to complications and disease progression. Thus, antiplatelet treatment in these patients may be essential to reduce their high mortality rate. Antiplatelet therapy for prevention of secondary vascular events is the cornerstone of pharmacological intervention in PAD. Based on current evidence, treating patients with PAD with antiplatelet drugs appears to be effective in reducing the risk of coronary and cerebrovascular events, in maintaining arterial and graft patency, and in slowing progression of disease. On the other hand, several studies indicated, that platelets in patients with PAD are relatively aspirin-resistant. The data from the CAPRIE Trial suggest a clinically and statistically significant better risk reduction with clopidogrel than with aspirin in patients with PAD. Aspirin alone should no longer be considered the optimal therapy for PAD.
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PMID:[Antiplatelet therapy in patients with peripheral arterial disease (PAD)]. 1548 53

Eighteen million Americans have type 2 Diabetes Mellitus (DM) while another 40 million have impaired glucose tolerance. Atherosclerotic heart disease is the leading cause of death in patients with diabetes mellitus. In addition to the increased risk for CardioVascular Disease (CVD), patients with diabetes have a worse prognosis than nondiabetics when they suffer an ischemic event. Insulin resistance is increasingly recognized as a chronic, low-level, inflammatory state. Hyperinsulinemia has been proposed as the forerunner of hypertension, low high-density lipoprotein cholesterolemia, hypertriglyceridemia, abdominal obesity, and altered glucose tolerance, linking all these abnormalities to the development of coronary vascular disease. Atherosclerosis and insulin resistance share similar pathophysiological mechanisms, due to the actions of proinflammatory cytokines. The dynamic inflammatory milieu found in diabetes explains the susceptibility of diabetics to CVD and the potential mechanism by which aspirin may prevent CVD in diabetics. Aspirin decreases the risk for CVD in diabetic patients by a variety of established and novel mechanisms. Therapeutic strategies that lesson the CVD risk in diabetic patients, including the use of aspirin for primary and secondary prevention, are potentially very important. This review article addresses the antiatherosclerotic effects of aspirin, the potential anti-diabetic effects of aspirin, and the clinical trial evidence for CVD prevention by aspirin in diabetics. We also present recommendations for the use of aspirin in the diabetic population and the current guidelines put forth by the American Heart Association and by the American Diabetes Association.
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PMID:Prevention of cardiovascular complications of diabetes mellitus by aspirin. 1549 69

The hemodynamics was intraoperatively studied in 43 patients with multicentric atherosclerosis, ASA III-IV, operated on the peripheral vessels of legs with balanced anesthesia based on subarachnoid block. It was established in regional sympathetic block and in the course of the whole surgery that the parameter of AP were decreased by 20-25%, those of heart rate--by 15% and of TPVR--50%, whereas, the parameters of cardiac performance were stable. The authors discuss the specificity of hemodynamic restructuring under subarachnoid block in patients with at surgical risk due to vascular pathology.
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PMID:[Subarachnoid anesthesia in patients with high surgical risk]. 1557 29

Remnant-like particles (RLPs) have been reported to promote atherosclerosis and to have effects on platelet function. We studied the effects of RLP on shear-induced platelet activation and their inhibition by antiplatelet agents in vitro. RLP were separated using two monoclonal antibodies, anti apo B-100 and anti apo A-I. These RLP fractions were added to whole blood (WB) or platelet-rich plasma (PRP) in serial dilution of 1, 10 or 100 microg RLP triglyceride (TG) per ml of total sample volume. These samples were incubated, and then stimulated with a high shear stress of 108 dyn/cm(2). Shear-induced platelet aggregation (SIPA) was calculated from the percentage of single platelet loss. P-selectin expression on platelet surface and platelet-derived microparticle (PMP) generation were measured before and after stimulation with shear stress using flow cytometer. SIPA was significantly enhanced by RLP in WB but not in PRP. This enhancing effect was not dose-dependent and was greatest at 10 microg TG/ml. P-selectin expression induced by shear stress was only enhanced by RLP at a concentration of 100 microg TG/ml in both WB and PRP, while generation of PMP induced by shear stress was only enhanced by RLP at a concentration of 100 microg TG/ml in WB. Aspirin inhibited only the enhancement of SIPA by RLPs, while cilostazol inhibited the enhancement of not only SIPA but also p-selectin expression and PMP generation by RLPs.
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PMID:Effect of remnant-like particle on shear-induced platelet activation and its inhibition by antiplatelet agents. 1561 44

Matrix metalloproteinases (MMPs) play an important role in many biological and pathological processes including tissue remodeling, wound healing, inflammation, atherosclerosis, and cancer. Numerous publications have supported the concept that activated MMP-2 enhances agonist-induced platelet aggregation and activated MMP-9 inhibits platelet aggregation. In this study, we demonstrated that the organomercurial compound, 4-aminophenyl mercuric acetate (APMA), which is routinely employed to activate latent MMPs at a concentration of 1000 microM, induces platelet aggregation at low concentration (5 microM) and inhibits agonist-induced platelet aggregation at concentrations >or= 50 microM. Activated MMP-2, MMP-1, and MMP-9, following removal of APMA by ultrafiltration through an anisotropic membrane, exert no independent effect on platelet aggregation. Acetylsalicylic acid and BAPTA inhibited APMA-induced platelet aggregation indicating that the APMA mediated pathway of platelet activation is dependent upon thromboxane and calcium signaling. Zinc chelation with 1,10-phenanthroline, which inhibits zinc-dependent proteins including metalloproteinases, also abrogated platelet functional responses to APMA. Additional studies will be required to clarify the mechanism of the biphasic effect of APMA on platelet aggregation.
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PMID:The organomercurial 4-aminophenylmercuric acetate, independent of matrix metalloproteinases, induces dose-dependent activation/inhibition of platelet aggregation. 1571 50

Type 2 diabetes is increasingly common worldwide and is beginning to strike younger age groups. Almost 90% of all patients with diabetes show insulin resistance, which also precedes the first symptoms of diabetes. The mechanisms underlying the development of insulin resistance are not well understood. In recent years, several studies have been published that implicate subclinical chronic inflammation as an important pathogenetic factor in the development of insulin resistance and type 2 diabetes. This opens new perspectives for diagnosis and treatment of early insulin resistance and incipient glucose intolerance. Surrogate markers for this low-grade chronic inflammation include CRP, IL-6 and TNF-alpha. Some antidiabetic agents, for example, glitazones that reduce insulin resistance, and insulin itself, reduce inflammation. Conversely, antiinflammatory drugs (ASA/NSAID) may improve glucose tolerance. Vasoactive drugs that are often prescribed to people with diabetes, for example, statins and ACE inhibitors/angiotensin receptor antagonists, also counteract inflammation and reduce the risk of type 2 diabetes. More specific and sensitive biomarkers should be identified, which may predict early disturbances in insulin sensitivity and cardiovascular risk. Also, inflammatory signalling pathways need to be explored in greater detail, and may form the basis of drugable targets against the epidemic of insulin resistance and atherosclerosis.
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PMID:Inflammation and the etiology of type 2 diabetes. 1599 Dec 54

There is a close inter-relationship between oxidative stress, coagulation, inflammation, and smooth muscle cell growth as key components of atherosclerosis (Fig. 1). As an analgesic and anti-pyretic, aspirin has been in use for over a century. It acetylates the COX enzyme, irreversibly inhibiting the formation of prostaglandin. Its action on platelet TxA2 has highlighted its role as an anti-thrombotic agent in cardiovascular patients. Over the last two decades, unique anti-inflammatory properties of aspirin not shared by other non-steroidals have been discovered. Aspirin biotransforms into salicylate, which has diverse but potent anti-inflammatory properties. As we strive to better understand the concepts of atherogenesis, chronic inflammation, oxidative stress, and endothelial activation, these novel effects of aspirin provide new insights as to how this wonder drug works. These effects of aspirin alter many, if not all, components of the atherogenesis cascade shown in Fig. 1.
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PMID:Relevance of platelet-independent effects of aspirin to its salutary effect in atherosclerosis-related events. 1614 21


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