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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present article deals with the pathophysiological role of serotonin in cardiovascular disease and in other disorders that are accompanied by cardiovascular pathophysiological events. The distribution of serotonin over various organs and tissues and the presence of several types of 5-HT receptors would suggest a rather important physiological role of serotonin. However, a modest serotonergic role could only be shown for the microcirculation and for the regional circulation of the brain and the intestinal wall. An important pathological role of serotonin in the carcinoid syndrome, in migraine, and in peripheral vascular disease is beyond debate, although many details remain to be established. The possibility that serotonergic mechanisms contribute to Raynaud's phenomenon and other vasospastic disorders is the subject of present discussions, although firm evidence for this view is not widely available. An involvement of peripheral serotonin in the genesis and maintenance of essential hypertension seems very unlikely, although vascular damage due to hypertension is probably enhanced by serotonin released from aggregating platelets. This ancillary process is, in particular, to be anticipated in older patients, with vascular walls predamaged by atherosclerosis. For this reason, pharmacological blockade of 5-HT2 receptors may be of potential therapeutic benefit in this category of patient. Finally, the involvement of central serotonergic mechanisms in hypertensive disease cannot be ruled out.
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PMID:Pathophysiological relevance of serotonin. 244 63

Generation of thromboxane A2 (TxA2) and prostacyclin (PGI2) at the site of platelet-vessel wall interaction, i.e. in blood emerging from a standardized injury of the microvasculature made to determine skin bleeding time was investigated in 7 patients with atherosclerosis (angiographically verified obstructions of the femoral arteries) and in 7 normal control subjects apparently free of atherosclerotic lesions. Similar amounts of TxA2 (measured as thromboxane B2, TxB2) were generated at the site of plug formation in the patients with peripheral vascular disease (PVD) and in the control subjects. Significantly lower levels of PGI2 (measured as 6-keto-prostaglandin F1 alpha, 6-keto-PGF1 alpha) were found in blood from an injury of the microvasculature in the patients compared with the controls. These data do not suggest a major role of the platelet prostaglandin metabolism in the development of atherosclerosis. However, decreased synthesis of PGI2 by endothelial cells might contribute to the development and/or progression of atherosclerotic lesions. In the patients with PVD, low-dose aspirin (50 mg/day for 7 days) resulted in a greater than 90% inhibition of the TxB2 production at the site of plug formation. Following low-dose aspirin 6-keto-PGF1 alpha levels were below 20 pg/ml (limit of sensitivity of our radioimmunoassay procedure) in the majority of the samples. We therefore conclude that in patients with PVD a decreased synthesis of PGI2 by endothelial cells might contribute to the progression of atherosclerosis. Furthermore, low-dose aspirin treatment results in a similar inhibition of the platelet prostaglandin generation as recently observed in healthy subjects.
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PMID:Thromboxane A2 and prostacyclin generation in the microvasculature of patients with atherosclerosis--effect of low-dose aspirin. 250 52

The authors report the principal clinical models in which inhibitors of platelet aggregation were used to prevent the clinical complications of atherosclerosis. The models at risk which were considered include unstable angina, TIAs, myocardial infarction and atherosclerotic vascular disease of the lower limbs. Overall, the studies suggest the value of this therapy for the prevention of cardiovascular accidents. TIAs, unstable angina and myocardial infarction are the models which provide the best evidence for this; however, the effectiveness of this therapy in peripheral vascular disease, while showing positive results, needs to confirmed by further clinical studies. Lastly, therapy with inhibitors of platelet aggregation has been shown to be useful in the prevention of aortocoronary bypass occlusion; however, its efficacy has been shown only when therapy is initiated early.
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PMID:Clinical use of antiplatelet therapy. 251 Nov 6

We followed 19 men and 19 women with asymptomatic carotid stenosis up to 30 months to determine whether hematologic or lipid abnormalities could identify those individuals developing progressing carotid atherosclerosis (defined as an increase in mean percent stenosis greater than or equal to 19% or an increase in a single region of greater than or equal to 23%) on B-mode carotid ultrasonography performed at 2- to 6-month intervals. Our patients demonstrated increased beta-thromboglobulin, platelet factor 4, and fibrinogen compared with age-matched controls. Eight patients developed progression of carotid stenosis, and this group had higher baseline low-density lipoprotein (LDL) and fibrinogen than the 30 nonprogressing patients. Multiple regression analyses of age, sex, smoking, coronary artery disease, peripheral vascular disease, diabetes, hypertension, and baseline high-density lipoprotein (HDL), HDL2, HDL3, LDL, beta-thromboglobulin, platelet factor 4, and fibrinogen identified coronary artery disease and elevated LDL and fibrinogen as the only independent variables significantly associated with the progressing group. We conclude that, in patients with carotid atherosclerosis, a combination of coronary artery disease and elevated LDL and fibrinogen will predict with 88% accuracy whether the patient will have progressing carotid stenosis.
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PMID:Prediction of carotid stenosis progression by lipid and hematologic measurements. 218 78

Polyunsaturated fatty acid (PUFA) components of the diet, especially of the omega-3 variety, protect against atherosclerosis and its related thrombotic complications. Mechanisms involved probably involve the eicosanoids. Classic PGE1 has now found a role in the treatment of peripheral vascular disease. Prostacyclin (PGI2) discovered over ten years ago has also been introduced into clinical medicine; orally active analogs are being introduced with clinical potential in a variety of atherosclerotic and thrombotic disorders. "Endothelium-derived relaxing factor (EDRF)" has been identified with nitric oxide, an active metabolite of the classic nitrodilator compounds, which (like NO itself) is synergistic with prostacyclins in inhibition of platelet activation, but without similar synergistic effects on vasodilation. This finding is of considerable importance both from physiological and therapeutic standpoints. The therapeutic efficacy of acetylsalicylic acid (ASA, aspirin) in the secondary prevention of myocardial infarction is now established. For primary prevention, it is probably inferior to diet (e.g. fish oil) and lifestyle changes due to increased incidence of cerebrovascular bleeding. The unfulfilled therapeutic promise of thromboxane synthesis inhibitors may be overcome by introduction of dual TX receptor/synthesis inhibitors. Recent advances suggest that PGE1, prostacyclin analogs and high dose fish oil could act beneficially against background nitrodilator therapy in preventing thrombosis and mitogen-stimulated restenosis following thrombolytic or surgical treatment of coronary artery occlusion.
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PMID:Therapeutic impact of eicosanoids in atherosclerotic disease. 269 16

Among the considerations affecting the therapeutic approach to patients with atherosclerosis of the lower extremities is their associated risk of death, myocardial infarction, stroke, and limb loss. To investigate the relationship of these events to the severity of peripheral vascular disease we undertook a 6-year review of 247 consecutive patients undergoing lower extremity noninvasive vascular assessment. There were 130 men and 117 women with a mean age of 65 +/- 15 years. Patients were categorized into four groups according to their ankle-brachial pressure indexes at their first visit. Ninety-seven patients had normal indexes (greater than or equal to 0.92), 86 had indexes of 0.50 to 0.91, 39 had indexes of 0.31 to 0.49, and 25 had indexes within the ischemic range, less than or equal to 0.30. At 6 years 64% of the patients with ischemic indexes were dead. This incidence was significantly higher than that of any other patient category (p less than 0.01). Diabetes also had a significantly adverse effect on survival. The incidence of stroke and myocardial infarction was similar for all disease groups. Thirteen percent and 32% of patients with indexes of 0.31 to 0.49 and less than or equal to 0.30, respectively, underwent limb amputation. We conclude that patients with evidence of mild to moderate peripheral vascular disease have a survival rate and risk of vascular-related disorders similar to those of patients of similar age with little evidence of disease, whereas an ankle-brachial pressure index less than or equal to 0.30 is associated with a malignant prognosis.
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PMID:Relationship of severity of lower limb peripheral vascular disease to mortality and morbidity: a six-year follow-up study. 272 57

Due to the recent knowledge that the distribution of fat deposits would be a better predictor of cardiovascular disease than the degree of obesity, some risk factors for atherosclerosis were evaluated in middle age type II male diabetics and in obese subjects with and without glucose intolerance. In non-insulin dependent diabetes, abdominal adiposity reflected by the waist/hip-circumference (WHR) was related to parameters of metabolic control, lipid parameters, blood rheology, insulin status, hypertension and known vascular complications in three different groups. In the groups with abdominal obesity, the mean annual HbA1 is significantly (p less than 0.01) higher than the group without an abdominal fat mass distribution. Atherogenic index is significantly increased in the group with the highest WHR. HDL-cholesterol levels are significantly decreased in both groups with upper body fat distribution. A highly significant (p less than 0.001) correlation was present between WHR and HDL-cholesterol and WHR and total/HDL-cholesterol ratio; this significant correlation remains after correction for body mass index. Whole blood and plasma viscosity and fibrinogen levels are significantly (p less than 0.05) increased in diabetics with upper body fat accumulation and could be compared to patients with proven coronary ischemic heart disease. The frequency of peripheral vascular disease, coronary ischemic heart disease and hypertension is most prominent in diabetics with an abdominal fat mass distribution. Systolic blood pressure even seems to be increased in non-obese diabetics with the highest WHR. A correlation could be found between WHR and both systolic and diastolic blood pressure. When corrected for body mass index the same significant correlation between WHR and blood pressure remained. Both fasting and postprandial insulin and C-peptide values may be the link between abdominal fat deposits and all metabolic disturbances. These results confirm the negative effect of an excess of abdominally located fat cells, even without manifest obesity, on diabetes metabolic control, lipid fractions, hypertension, insulin behaviour, blood rheology and cardiovascular complications. In obese patients with upper body fat accumulation a higher prevalence of glucose intolerance and diabetes is present, in contrast to their counterparts with lower body fat deposit. Both fasting glycemia, insulin and insulin area are significantly (p less than 0.005) increased in the group with the greatest WHR.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Body fat mass distribution. Influence on metabolic and atherosclerotic parameters in non-insulin dependent diabetics and obese subjects with and without impaired glucose tolerance. Influence of weight reduction. 280 Jun 85

Previous work has shown that plasma and tissue concentrations of histamine are elevated in rats with experimental diabetes mellitus and that leucocytes and platelets from patients with peripheral vascular disease have a higher histamine content than those from controls. In the present study, we have measured: (a) plasma histamine concentrations; (b) leucocyte and platelet histidine decarboxylase (the enzyme responsible for the biosynthesis of histamine) in patients with diabetes mellitus (Types I and II) and peripheral vascular disease; and (c) platelet and leucocyte histamine content. Plasma histamine concentration was significantly higher in patients with diabetes and peripheral vascular disease respectively than that in age-matched controls. Leucocyte histidine decarboxylase activity in diabetic and peripheral vascular disease patients was similar to that in controls, while platelets had no histidine decarboxylase activity. The leucocyte and platelet content of histamine were greater in patients with peripheral vascular disease than those in controls, but they were not altered in diabetic patients. There was no correlation between plasma histamine concentration, leucocyte and platelet histamine content, and histidine decarboxylase activity. We conclude that plasma histamine is elevated in diabetics and in patients with peripheral vascular disease and that platelet and leucocyte histamine content is increased in the latter. This increase in platelet and leucocyte histamine content is not due to an increase in histidine decarboxylase activity of these cells. The increase in plasma and cellular histamine content may contribute to the pathogenesis of increased endothelial permeability in diabetes and to the pathogenesis of intimal damage in atherosclerosis.
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PMID:Plasma histamine concentrations are elevated in patients with diabetes mellitus and peripheral vascular disease. 291 44

A high surface density of the openings of the surface connected canalicular system (SCCS) has been observed in the freeze-fractured plasma membrane of circulating platelets in rabbits fed an atherogenic diet and in hypercholesterolemic type IIa patients. In vitro tests have revealed a correlation between the increased surface density of the SCCS openings and the initial steps of platelet activation. 8-Chlorocarbochromen, a new drug which enhances the in vivo release of prostacyclin from the arterial wall, has been found to be effective in reducing the high surface density of SCCS openings in platelets of rabbits on an atherogenic diet. The present study shows that circulating platelets from patients with peripheral vascular disease present a high surface density of SCCS openings compared to that observed in control subjects. After a single oral administration of 8-chlorocarbochromen, a reduction of the high number of these openings has been observed. Likewise, beta-thromboglobulin levels were found to be high in the patients and to be significantly reduced after oral administration of the drug. This study shows ultrastructural modifications of platelets in conditions related to atherosclerosis and includes data on the effectiveness of 8-chlorocarbochromen in reducing the platelet activation of these patients.
Atherosclerosis 1986 Nov
PMID:Ultrastructural modifications of the platelet plasma membrane in vascular diseases and the effect of a carbochromen derivative as studied by freeze-fracture and computer measurement. 294 12

Increased arterial pulse wave velocity (PWV) and decreased Doppler-shifted Fourier pulsatility index (PI) have been utilized clinically to diagnose the presence and severity of peripheral vascular disease. We have examined the relationships between these two diagnostic indices and several lipoprotein atherogenic risk factors, e.g., serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein-cholesterol (HDL-C), and low-density lipo-protein-cholesterol (LDL-C) among 74 healthy male volunteers, aged 20 to 56 yr. The Doppler signal from the radial artery was digitized and processed with the Hamming window and 512-point fast Fourier transform to obtain frequency power spectra and PI index by a desktop computer. PWV was determined on the computer by dividing the distance between two pressure transducers placed over the radial and carotid arteries by the transit time difference between the maximal first derivatives (dP/dt) of the recorded arterial pulse waves. The results indicated that PI was inversely related to TC, LDL-C, and TG (r = -0.50, -0.41, -0.54, respectively, P less than 0.001), but evidenced a positive relationship with the HDL-C/TC ratio (r = 0.69, P less than 0.001). PWV was also significantly correlated to TC (r = 0.40) and TG (r = 0.42), but was inversely associated with the HDL-C/TC ratio (r = -0.45, P less than 0.001). These findings are consistent with the current theory relating lipids to the pathology of atherosclerosis.
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PMID:Arterial pulse wave velocity, Fourier pulsatility index, and blood lipid profiles. 295 72


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