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Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cardiovascular disease is a major cause of death. There is evidence that this disease is predicted and its progression influenced by various factors (e.g. hyperlipidaemia). In this review, we consider aspects of platelet structure and function which may explain how this cell type contributes to the pathogenesis of vascular disease. The platelet also contains bioamines (serotonin, 5-HT; histamine) which are potent vasoactive substances. Studies involving patients with peripheral vascular disease (PVD) where abnormalities in platelet function (platelet aggregation and platelet shape change) and in bioamine status (vascular, platelet and plasma bioamine concentrations) are reviewed. We also discuss how platelet activation (in vitro) and plasma lipids influence intraplatelet bioamine status. Finally, we report in vitro evidence of the effect of two drugs prescribed to PVD patients: aspirin and naftidrofuryl. Aspirin is an ineffective inhibitor of 5-HT-induced whole blood platelet aggregation whereas naftidrofuryl is effective in the presence or absence of aspirin. By identifying and altering the factors which contribute to the pathogenesis of atherosclerosis we will be better equipped to prevent, reverse or retard this process.
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PMID:Serotonin, histamine and platelets in vascular disease with special reference to peripheral vascular disease. 134 86

Oxidative modification of LDL renders it immunogenic and autoantibodies to epitopes of oxidised LDL, such as malondialdehyde (MDA)-lysine, are found in serum and recognise material in atheromatous tissue. However, there has been no prospective study to assess the importance of oxidised LDL among patients with vascular disease. We compared the titre of autoantibodies to MDA-modified LDL and native LDL in baseline serum samples of 30 eastern Finnish men with accelerated two-year progression of carotid atherosclerosis and 30 age-matched controls without progression. Neither group had specific antibody binding to native LDL. A titre was defined as a ratio of antibody binding to MDA-LDL/binding to native LDL. Cases had a significantly higher titre to MDA-LDL (2.67 vs 2.06, p = 0.003). Cases also had a greater proportion of smokers (37% vs 3%), higher LDL cholesterol (4.2 mmol/l vs 3.6 mmol/l), and higher serum copper concentration (1.14 mg/l vs 1.04 mg/l). Even after adjusting for these variables and the severity of baseline atherosclerosis, the difference in antibody titre remained significant in a multifactorial logistic model (p = 0.031). Thus, the titre of autoantibodies to MDA-LDL was an independent predictor of the progression of carotid atherosclerosis in these Finnish men. Our data provide further support for a role of oxidatively modified LDL in atherogenesis.
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PMID:Autoantibody against oxidised LDL and progression of carotid atherosclerosis. 135 50

Retrospective analysis suggests that there is increased mortality from vascular disease in hypopituitary adults, but vascular status before death is unknown. High resolution B-mode ultrasonic imaging of both carotid and femoral arteries was therefore done in 34 adult hypopituitary patients on routine replacement therapy and was compared with that in 39 matched controls. Changes were related to risk factors for vascular disease. Carotid intima-media thickness was greater in patients than in controls (mean [SD] 0.74 [0.16] vs 0.65 [0.13] mm, p < 0.02). This difference was seen in middle-aged and elderly patients. More patients than controls had one or more atheromatous plaques (65% vs 41%, p < 0.05). The percentage of individual arteries with a plaque was also higher in patients (32% vs 18%, p < 0.005). In multiple regression analysis, patients' age was the dominant factor determining carotid intima-media thickness. Symptom-free adults with hypopituitarism show an increased prevalence of atherosclerosis.
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PMID:Detection of premature atherosclerosis by high-resolution ultrasonography in symptom-free hypopituitary adults. 809 46

In order to clarify whether cystathionine beta-synthase (CBS) could differentiate groups of patients with various vascular diagnosis, CBS was studied in cultured human skin fibroblasts from 99 human subjects diagnosed as homozygotes or heterozygotes for CBS deficiency or suffering from atherosclerotic vascular disease or Down's syndrome (prone to less atherosclerosis). In addition, embryonic human skin fibroblasts and controls were analysed for CBS. We found significant group differences but the overlap in the hetero- and homozygotes for CBS deficiency was too extensive to allow any individual diagnosis based on cell culture studies. CBS activity was significantly lower in the atherosclerotic patients as compared to control subjects. The difference was mostly due to much higher CBS activity in the younger controls. Age dependency was markedly emphasized by very high values from embryonic cells. A strong negative correlation was noted for age and CBS activity in control subjects but not in the atherosclerotic patients. The results are important for the discussion of homocysteine in atherosclerosis and point to the importance of donor age on CBS activity in cultured cells. In addition, diagnosis of hetero-homozygosity for CBS activity is not possible on an individual basis by this method. Further studies in cell culture systems are needed to investigate if young patients (less than 45 years old) with atherosclerotic disease could be identified by low CBS activity in fibroblast cultures as indicated by this study.
Atherosclerosis 1992 Jun
PMID:Age dependency of cystathionine beta-synthase activity in human fibroblasts in homocyst(e)inemia and atherosclerotic vascular disease. 138 57

There is accumulating evidence that free radicals may contribute to various diseases such as cancer or cardiovascular disease. Possible health hazards can to some extent be prevented by the body's multilevel defense system against free radicals, which comprises, besides others, antioxidant vitamins. The 12-year mortality follow-up of 2,974 participants of the Basal Study allowed to test the hypothesis that low antioxidant vitamin plasma concentrations (vitamin A, C, E and carotene) were associated with increased death from cancer of various sites and death from atherosclerosis such as ischemic heart disease and stroke, respectively. For the analysis 204 cancer cases, 132 fatalities from ischemic heart disease (IHD) and 31 deaths from cerebral vascular disease were available. Cancer mortality. Overall mortality from cancer was associated with low mean plasma levels of carotene adjusted for cholesterol (p less than 0.01) and of vitamin C (p less than 0.01). Bronchus and stomach cancers were associated with a low mean plasma carotene level (p less than 0.01). Subjects with subsequent stomach cancer had also lower mean vitamin C and lipid-adjusted vitamin A levels than survivors (p less than 0.05). Calculating the relative risk with exclusion of mortality during the first two years of follow-up, low plasma carotene was associated with an increased risk for bronchus cancer (RR 1.8, p less than 0.05), and the small number of stomach cancer cases (RR 2.95, p less than 0.05) low plasma levels of carotene and vitamin A with all cancer types (RR 2.47, p less than 0.01), and low plasma retinol in older subjects (greater than 60 years) with lung cancer (RR 2.17, p less than 0.05). Studies in other cohorts with a poor vitamin E status revealed an increased risk of subsequent cancer at low vitamin E levels as well. It is concluded that low plasma levels of all major essential antioxidants are associated with an increased risk of subsequent cancer mortality. Cardio-vascular mortality. Plasma carotene concentration below quartile 1 was associated with an increased risk for IHD (RR 1.53, p = 0.02). The same was true for low levels of both carotene and vitamin C (RR = 1.96, p = 0.022). The risk of cerebrovascular death was elevated in subjects with low carotene in the presence of low vitamin C plasma concentration (RR 4.17, p less than 0.01). These data confirm and extend recent findings on an inverse correlation of beta-carotene and vitamin C respectively to CVD.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Inverse correlation between essential antioxidants in plasma and subsequent risk to develop cancer, ischemic heart disease and stroke respectively: 12-year follow-up of the Prospective Basel Study. 145 Jun

The development of laboratory techniques for the culturing of vascular endothelial and smooth-muscle cells during the 1970s, followed by the rapid advances in molecular and cell biology during the 1980s, provided the foundation for the identification of growth factor and cytokine networks involved in maintenance of the normal vasculature as well as participating in diverse pathologic processes involving blood vessels. Vascular cells can produce and respond to a vast array of biochemical messengers that control cell replication, differentiation, and many specific cell functions. Investigators are beginning to explore the changes in the patterns of messengers exchanged between the vascular cells and infiltrating leukocytes during the initiation and progression of atherosclerosis. A variety of in vitro and in vivo studies have indicated that growth factors and cytokines that mediate the critical processes of inflammation and wound healing also play a central role in vascular disease. Indeed, many view atherosclerosis as the result of excessive or prolonged chronic inflammation and wound healing in response to diverse injurious stimuli to cells of the vessel wall. Vascular injury may result from many varied and interacting forces, including nutritional and metabolic abnormalities such as hyperlipidemias or elevated homocysteine, mechanical forces associated with hypertension, exogenous toxins including those found in cigarette smoke, abnormally glycated proteins associated with diabetes mellitus, oxidatively modified lipids or proteins, and, possibly, viral infections. Ultimately, a greater understanding of the activated cytokine and growth factor networks within the vascular wall following injury and during atherogenesis will allow clinical scientists to identify steps susceptible to therapeutic intervention using recombinant cytokines, antibodies, soluble receptors, or receptor antagonists. Other therapeutic strategies may involve the transfection of specific genes, which may inhibit atherosclerosis, into vascular cells at sites prone to lesion formation.
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PMID:Cytokines and growth factors in atherogenesis. 145 74

High density lipoprotein subfraction 2 (HDL1)-cholesterol level is usually decreased in Type 2 (non-insulin-dependent) diabetes. A study was carried out in 251 Type 2 diabetic patients (106 males [M], 145 females [F]) and in 120 non diabetic controls in order to determine the influence of hypertriglyceridaemia and obesity on the HDL2-cholesterol level and to analyse the relationship between HDL2-cholesterol level and atherosclerosis (coronary heart disease, peripheral atherosclerosis or cerebral vascular disease), in Type 2 diabetes. Influence of hypertriglyceridaemia and obesity on HDL2-cholesterol level was studied by comparing the mean values of HDL2-cholesterol between diabetics and controls, after controlling for hypertriglyceridaemia and obesity, and by a multiple linear regression test. A stepwise logistic regression was performed to analyse the association between the prevalence of atherosclerosis and several variables: age, duration of diabetes, hypertension, cigarette smoking, body mass index, mean glycaemia, total cholesterol, triglyceride, HDL-cholesterol, HDL2-cholesterol and HDL3-cholesterol levels. In both men and women, when both of the factors (hypertriglyceridaemia and obesity) were present of when only one was, HDL2-cholesterol level was significantly lower in the diabetic population, compared with controls. But when obesity and hypertriglyceridaemia were absent, HDL2-cholesterol level, in the diabetic population, was not significantly different from controls (M: 17.9 +/- 13.3 vs 20.5 +/- 13.8 mg/dl: NS; F: 30.1 +/- 21.5 vs 27.6 +/- 14.2 mg/dl: NS).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Influence of obesity and hypertriglyceridaemia on the low HDL2-cholesterol level and on its relationship with prevalence of atherosclerosis in type 2 diabetes. 145 17

The most serious complication of diabetes mellitus is clinical nephropathy. The development of persistent proteinuria (urinary excretion of more than 300 mg albumin/24 hours) implies an extremely high risk of early death. Renal failure is the most frequent cause of death but the mortality of cardiovascular diseases is also increased. Besides the link between albuminuria (nephropathy) and atherosclerosis in coronary arteries, albuminuria is also a predictor of microangiopathy in other organs than the kidneys. The annual incidence of proliferative retinopathy in early nephropathy is 10-15% compared to only 1% in patients without nephropathy. Also signs of cardiomyopathy have been demonstrated in early nephropathy. Further we have described markers of universal endothelial damage in these patients, and we hypothesize that albuminuria not only is a predictor of renal disease but also of widespread vascular disease. Long-term improvement of metabolic control by use of insulin infusion pumps and early antihypertensive treatment seem to stop the further progression of early diabetic nephropathy and to significantly improve the prognosis of clinical nephropathy.
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PMID:Diabetic retinopathy, nephropathy and neuropathy. Generalized vascular damage in insulin-dependent diabetic patients. 149 Jun 95

Hyperhomocysteinemia arising from impaired methionine metabolism, and usually due to a deficiency of cystathionine beta-synthase is a significant and independent risk factor for symptomatic vascular disease. It is not known if hyperhomocysteinemia in apparently healthy asymptomatic subjects is associated with atherosclerosis and whether such a relationship is independent of conventional risk factors. The prevalence of asymptomatic extracranial carotid artery atherosclerosis was determined by duplex ultrasound examination in 25 obligate heterozygotes with respect for cystathionine beta-synthase deficiency (whose children were known to be homozygous for this genetic defect) and in 21 controls. Hyperhomocysteinemia was determined by a standard methionine-loading test and conventional risk factors were also recorded. Twelve of 25 obligate heterozygotes and 8 of 21 normal controls had evidence of extracranial carotid artery atherosclerosis. Hyperhomocysteinemia as a genetic trait was not a significant risk marker, but the actual homocysteine level was associated with an increased risk of carotid disease. After adjustment for the effects of other significant risk factors, the odds ratio of hyperhomocysteinemia for carotid disease was 1.038 per unit increase in homocysteine level (P = 0.03). Hyperhomocysteinemia is a weak risk factor for asymptomatic extracranial carotid atherosclerosis and the relative risk associated with this genetic trait is less than that observed in a study of patients presenting with clinical manifestations of vascular disease.
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PMID:Hyperhomocysteinaemia: a risk factor for extracranial carotid artery atherosclerosis. 151 57

Although platelets can contribute to atherosclerosis and its thromboembolic complications in the nondiabetic population, the role of platelets in enhanced vascular disease in the diabetic population remains unclear. Most studies indicate that platelet function in vitro is enhanced in platelets from people and animals with diabetes, and the mechanisms are being identified. There remains some controversy about whether platelet changes occur before, and therefore could contribute to, vascular complications or whether they are secondary to vascular disease. It is possible that only intervention trials to determine if inhibiting platelet function limits the progression of vascular disease in diabetic patients will definitively answer this question. The earlier premise that enhanced activity of the arachidonate pathway is responsible for the hypersensitivity of platelets from diabetic humans needs to be modified to recognize that additional mechanisms are involved in platelet activation and are modified in people with diabetes and also that altered activity of the arachidonate pathway may reflect changes in earlier pathways involved in platelet activation. Clearly, alterations in these nonarachidonate pathways need to be taken into account when considering the appropriate antiplatelet agents to use in intervention trials. Information about whether hypersensitivity of platelets from people with diabetes persists in vivo and, if so, how this influences platelet-vessel wall interactions and thrombotic tendencies needs to be pursued more intensely in suitable animal models so that the theories developed from studies in vitro can be tested in the more complex environment in vivo. These are important areas for research in the future.
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PMID:Platelet abnormalities in diabetes mellitus. 152 32


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