Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypertension is a constellation of abnormalities, including metabolic disorders. The current approach to treatment of hypertension should not be dictated solely by measures to lower blood pressure. It must also take into consideration the effect of antihypertensive drug treatment on the development of atherosclerosis and many other important factors. Evidence from rabbit models and cell cultures indicates that calcium channel blockers are antiatherogenic through a variety of mechanisms. In addition to preserving endothelial function, these agents inhibit the following: Platelet aggregation Migration of monocytes and smooth-muscle cells into the intima Incorporation of low-density lipoprotein cholesterol into these cells Matrix formation Calcium overload in atherosclerotic lesions However, additional studies are needed to delineate the antiatherogenic effects of these and other antihypertensive agents.
 ...
PMID:Antiatherosclerotic effects of calcium channel blockers. 149 83

Animal experiments suggest an inhibitory effect of calcium entry blockers on arterial calcinosis and the formation of atherosclerotic plaques. Experiments with isolated tissues suggest various mechanisms for an antiatherosclerotic effect of calcium entry blockers. INTACT, the International Nifedipine Trial on Antiatherosclerotic Therapy, is the first study investigating, with a prospective, placebo-controlled, randomized, double-blind design, the influence of a calcium entry blocker (nifedipine 80 mg/day) on the progression of coronary atherosclerosis in patients with proven coronary artery disease. Study endpoints were changes of established coronary stenoses (diameter reduction greater than or equal to 20%), as well as the formation of new stenoses as documented by coronary angiography. Standardized coronary angiograms were taken before and after a treatment period of 3 years. The angiograms were quantitatively analyzed with the computer-assisted edge detection system CAAS. Of the 425 patients included in the study, 282 patients (134 on nifedipine and 148 on placebo) revealed no protocol violations. In the inclusion angiograms of these patients, 893 coronary stenoses were detected which were not significantly influenced in their development by nifedipine. However, 196 entirely new coronary lesions, 185 stenoses and 11 occlusions, were found in the follow-up angiograms. There were 78 lesions in 54 patients (40%) on nifedipine (0.58 new lesions/patient) and 118 lesions in 73 patients (49%; n.s.) on placebo (0.8 new lesions/patient; p = 0.031). In two other studies on the inhibiting effect of dihydropyridine calcium entry blockers on the progression of coronary artery disease in man defining angiographic endpoints, the drugs were also shown to reduce the number of newly formed significant coronary lesions. If further trials in man confirm a protective role of calcium entry blockers against the formation of atherosclerotic coronary lesions, a new strategy in the prevention of coronary artery disease has to be considered.
 ...
PMID:Concept of an antiatherosclerotic efficacy of calcium entry blockers. INTACT Investigators. 150 47

The purpose of this study was to determine if chronic administration of L-arginine, the precursor of endothelium-derived relaxing factor (EDRF), normalizes endothelium-dependent relaxation and decreases atherosclerosis in hypercholesterolemic animals. Male rabbits were fed (a) normal rabbit chow; (b) 1% cholesterol diet; or (c) 1% cholesterol diet supplemented by 2.25% L-arginine HCl in drinking water. Arginine supplementation doubled plasma arginine levels without affecting serum cholesterol values. After 10 wk, the thoracic aorta was harvested for studies of vascular reactivity and histomorphometry. Endothelium-dependent relaxations (to acetylcholine and calcium ionophore A23187) were significantly impaired in thoracic aortae from animals fed a 1% cholesterol diet. By contrast, vessels from hypercholesterolemic animals receiving L-arginine supplementation exhibited significantly improved endothelium-dependent relaxations. Responses to norepinephrine or nitroglycerin were not affected by either dietary intervention. Histomorphometric analysis revealed a reduction in lesion surface area and intimal thickness in thoracic aortae from arginine-supplemented animals compared to those from untreated hypercholesterolemic rabbits. This is the first study to demonstrate that supplementation of dietary L-arginine, the EDRF precursor, improves endothelium-dependent vasorelaxation. More importantly, we have shown that this improvement in EDRF activity is associated with a reduction in atherogenesis.
 ...
PMID:Antiatherogenic effects of L-arginine in the hypercholesterolemic rabbit. 152 25

The main objective of the study was to investigate the effect of the calcium antagonists Verapamil (2 mg.kg-1.day) and Nifedipine (1 mg.kg-1.day-1) on cholesterol (1%) induced atherosclerosis in rabbits. The drugs were administered s.c. twice daily over a period of 8 weeks. Blood lipid levels were determined three times during the experiment. After the experimental period the animals were killed and macroscopic changes on the aorta were recorded. For histochemical investigation samples were taken from the arch of the aorta and coronary artery. In cryostat sections lipids were determined by Sudan black B and Fett rot 7 B and the following enzymes were assayed: acid phosphatase, non-specific and acid esterase, acid beta-galactosidase, dipeptidyl peptidase I and II, and glucose-6-phosphate dehydrogenase. Following treatment with the calcium antagonists the levels of triacylglycerols and of total cholesterol were significantly increased in comparison with the control and diet groups. The ratio of HDL cholesterol to total cholesterol decreased in the treated animals. In lipoid plaques the activity of enzymes was enhanced in all experimental animals. There were however no qualitative differences in the composition of plaques between individual groups, which exhibited only quantitative differences. The number of migrating macrophages was increased only in the nifedipine treated animals. The extent of plaques was significantly decreased after nifedipine treatment, whereas verapamil failed to exert antiatherogenic effect. (Tab. 2, Fig. 4, Ref. 22.).
 ...
PMID:[The effect of verapamil and nifedipine on the development of experimental atherosclerosis in rabbits]. 152 79

The early detection of coronary atherosclerosis may be impossible if we continue to depend on its pathophysiologic effects (ischemia) for our screening tests. Insoluble crystalline calcium phosphate, which is ubiquitous in our inorganic and biologic worlds, precipitates relatively early in atherosclerotic lesions. Since coronary calcification is specific for atherosclerosis and since calcium is a strong radiation absorber in the X-ray frequency range, sensitive radiographic techniques such as dual-energy subtraction fluoroscopy and ultrafast computed tomography hold promise as screening tests for this disease.
 ...
PMID:Radiographically detectable calcium and atherosclerosis: the connection and its exploitation. 152 43

The question whether some classes of antihypertensive drugs have an antiatherogenic action independent of the antihypertensive one has been investigated through a large series of experimental studies; on the other hand, clinical evidence is still rather scanty. Most experimental investigations have shown a significant antiatherogenic action of the antihypertensive compounds, but only when the drug is administered simultaneously with the atherogenic stimulus (mostly cholesterol feeding). When the drug is administered weeks or months after the beginning of atherosclerosis (as in the Watanabe heritable hyperlipemic rabbit), no antiatherogenic effect has been shown, with a single exception. Although the most numerous data available are on calcium antagonists, almost all antihypertensive classes tested have shown some favorable effect on some experimental model. The few clinical studies completed so far as on coronary patients; they have provided arteriographic evidence that various calcium-antagonists have little effect on well-developed lesions and display a beneficial action on new or early lesions only. Ultrasound studies are now underway to compare the effects of calcium-antagonists and diuretics on asymptomatic carotid atherosclerotic lesions in hypertensive patients.
 ...
PMID:The antiatherogenic effects of antihypertensive drugs: experimental and clinical evidence. 154 Oct 43

Oxidation of low density lipoprotein increases its atherogenic potential. During oxidation there is an extensive conversion of lecithin to lysolecithin. In rat aortic smooth muscle cells, 2-25 micrograms/ml lysolecithin elevated cytosolic calcium concentration up to 560%. Lysolecithin (10-20 micrograms/ml) increased [3H]thymidine incorporation from 15 cpm/mg cell protein (controls) up to 189 cpm/mg cell protein. Lysolecithin (10 micrograms/ml) potentiated the PDGF-induced (50 ng/ml) [3H]thymidine incorporation up to 6.3 times. The results indicate that lysolecithin could induce mechanisms, by which oxidized low density lipoproteins could promote cell growth and thus contribute to atherosclerosis.
 ...
PMID:Lysolecithin actions on vascular smooth muscle cells. 154 86

Hypertension is quite common in the elderly population. Isolated systolic hypertension and diastolic hypertension are associated with cardiovascular complications. Like younger patients, the elderly may have labile hypertension. On the other hand, pseudohypertension, auscultatory gap, and postural hypotension are peculiar to the elderly. Obesity, atherosclerosis, arteriosclerosis, baroreceptor insensitivity, decline in renal function, physical inactivity, and insomnia are factors that can lead to or aggravate hypertension in older patients. Secondary hypertension should be suspected if elevated blood pressure first appears late in life or becomes resistant to previously adequate treatment. Spontaneous hypokalemia can indicate primary aldosteronism. Elevation in the serum creatinine level of a patient taking an angiotensin-converting enzyme (ACE) inhibitor suggests bilateral renovascular hypertension. The goal of antihypertensive therapy is to prevent morbidity, disability, and death from complications and to maintain quality of life. Psychosocial factors may play an important role in controlling hypertension. Nonpharmacologic treatment, such as weight loss, salt restriction, and exercise, should always be tried prior to and in conjunction with medical therapy. Antihypertensive drugs often cause side effects and should be prescribed with caution. Always start with a low dose and gradually increase it if necessary. All drugs that reduce blood pressure in the younger individual also work in the elderly. ACE inhibitors and calcium blockers are particularly useful because of their low incidence of adverse effects.
 ...
PMID:Hypertension in elderly patients. The special concerns in this growing population. 154 24

In this paper we demonstrate that near infrared Fourier transform Raman spectroscopy provides unprecedented biochemical information about the extent of atherosclerosis in human aorta. In particular, elastin, collagen, cholesterol, cholesterol esters, lipids, carotenoids, and calcium apatite deposits all can be discerned by using this technique, permitting study of each stage in the disease process. Additionally, these moieties can be detected over 1.5 mm below the irradiated surface of the tissue, possibly allowing extraction of three-dimensional information about the histology of atherosclerotic plaques. We propose that this technique may be utilized for in situ optical histochemical analysis of atherosclerosis in particular and human disease in general.
 ...
PMID:In situ optical histochemistry of human artery using near infrared Fourier transform Raman spectroscopy. 156 40

Cytokines belonging to the RANTES/SIS family are highly induced in a number of pathophysiological processes such as autoimmune disorders, cancers, atherosclerosis, and chronic inflammation. However, apart from their chemotactic activity on monocytes and particular lymphocyte types, the biological activities in the human system of this recently discovered cytokine family are largely unknown. Here we report that one family member, described as monocyte chemotactic protein 1 (MCP-1), strongly activates mature human basophils in a pertussis toxin-sensitive manner. MCP-1 causes a rise in the cytosolic free calcium level in basophils and monocytes, but not in other blood leukocyte types, and triggers basophil degranulation at low concentrations (ED50 = 3-10 nM). Thus, MCP-1 is a cytokine capable of directly inducing histamine release by basophils. Furthermore, MCP-1 promotes the formation of leukotriene C4 by basophils pretreated with interleukin 3 (IL-3), IL-5, or granulocyte/macrophage colony-stimulating factor. MCP-1-induced basophil mediator release may play an important role in allergic inflammation and other pathologies expressing MCP-1.
 ...
PMID:Monocyte chemotactic protein 1 is a potent activator of human basophils. 156 97


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>