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)

The von Willebrand factor is a high molecular weight protein which is synthesized by endothelial cells and appears in plasma and platelets. The main function of the factor is in mediating the adherence of platelets to the deendothelialized vessel wall. Animals with congenital deficiency of the factor do not develop the atherosclerotic lesions found in their normal counterparts. Elevated levels of the von Willebrand factor are observed in patients with atherosclerotic peripheral vascular disease, myocardial infarction, and diabetics with proliferative retinopathy. These increases in the factor may be due to the increased turnover rates of platelets and endothelial cells commonly seen in these disorders. Whether elevated levels of the von Willebrand protein constitute a unique risk factor for the development of atherosclerosis and vascular occlusive disease should be determined by studies currently in progress.
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PMID:Role of the von Willebrand factor in atherogenesis. 31 93

Maintenance hemodialysis and renal transplantation are increasingly used for treating diabetic patients with end-stage renal failure. The use of the artificial pancreas is able to prevent large blood glucose fluctuations in these patients with atherosclerosis, advanced retinopathy or neuropathy in which hyper- and hypoglycemia are potentially deleterious. For this purpose, we have developed and are utilizing an artificial pancreas easily utilizable without special training by the staff of a dialysis unit. This artificial pancreas uses a polarographic glucose electrode with a fast response time (45 to 90 seconds), a terminal display for operator communication, and a continuous digital and analogyl display for control of the running operation. There is also a printer to display in tabular and graphical form the values at any time during the operation. In this preliminary study, 7 patients have been studied: five under repetitive hemodialysis for four hours, 3 times a week; one treated by peritoneal dialysis for 12 hours, twice a week and one controlled during, and 48 hours after, renal transplantation. The macroscopic pancreas normalizes blood glucose under these circumstances, helps in a better understanding of blood glucose homeostasis in uremic patients under dialysis, leads to a more precise evaluation of insulin needs, may help to improve the nutritional status of the patients, and has an educational value for the patient and the medical staff.
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PMID:The use of the artificial pancreas in uremic diabetic patients. 39 76

Present methods of management of juvenile-onset diabetes mellitus do not prevent serious and debilitating complications affecting multiple organ systems. In an effort to reverse advanced forms of these complications, segmental transplantation of the pancreas has been performed on 10 patients, seven of whom simultaneously or subsequently received renal transplants. Long periods of normoglycemia (two to four and one-half years) were achieved in two patients who also maintained transplant kidney function. The course of these two patients is described to illustrate the possible value and limitations of the procedure. These patients had normal blood glucose levels, exhibited repeated normal intravenous glucose tolerance curves, and had repeated normal endogenous insulin levels. Their courses were characterized by (1) absence of problems related to pancreatic exocrine secretions into the bladder; (2) stable eye changes despite some episodes of hemorrhage from preexisting retinopathy; (3) vascular complications, including stroke and gangrene of extremities necessitating amputation despite successful femoropopliteal bypass grafting; (4) peripheral neuropathy; and (5) repeated infections. Both patients succumbed to vascular complications. Thus, pancreatic transplantation can maintain blood glucose and insulin at normal levels for extended periods of time. However, it does not reverse such complications as advanced retinopathy or atherosclerosis. Since the procedure may have value in preventing progression of these complications, it should be evaluated in patients with less advanced complications of diabetes.
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PMID:Long-term effects of pancreatic transplant function in patients with advanced juvenile-onset diabetes. 40 Jan 24

Considerable evidence points to a metabolic cause for the long-term complications of diabetes--neuropathy, retinopathy, nephropathy and atherosclerosis. Recent studies suggest potential benefits from controlling hyperglycemia as well as possible. However, the individual physician must analyze the evidence for himself and then decide on which principles to base the treatment of his patients.
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PMID:Diabetic control and the late complications of diabetes. 88 56

Microalbuminuria is diagnosed when the UAER is greater than 20 but less than 200 micrograms/min. The prevalence of microalbuminuria among diabetic patients is 15-20%. Persistent microalbuminuria in diabetic patients is a risk marker not only of renal disease, but also of proliferative retinopathy and cardiovascular morbidity and mortality. Even among nondiabetic individuals, those with microalbuminuria tend to have an increased cardiovascular morbidity. The established cardiovascular risk factors, such as smoking, elevated plasma cholesterol, fibrinogen, and hypertension, are seen more frequently in diabetic patients with persistent microalbuminuria than in normoalbuminuric diabetic patients of similar age, sex, and diabetes duration. However, these risk factors cannot by themselves explain the cardiovascular overmortality in these patients. In addition, insulin resistance or genetic disposition to hypertension or cardiovascular disease fails to be the missing link. Accumulating evidence suggests a common pathogenetic mechanism for microalbuminuria and premature atherosclerosis (i.e., qualitative alterations of the extracellular matrix, including decreased density and sulfation of HS-PG). Decreased density of HS in the glomeruli may lead to albuminuria and mesangial proliferation. In the intima of large vessel walls, decreased density and/or sulfation of HS may enhance several of the processes involved in premature atherosclerosis. Diabetes affects the composition and structure of the extracellular matrix in many ways and leads to decreased density and sulfation of HS-PG by several mechanisms. Genetic differences in the sulfation of HS and/or genetic defects in the coordinated biosynthesis of HS-PG might contribute to decreased concentration and sulfation of HS-PG in susceptible individuals. It is hoped that susceptibility genes can be identified soon, thereby making prevention of severe late diabetic complications more successful.
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PMID:Microalbuminuria. Implications for micro- and macrovascular disease. 139 15

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

Serotonin (5-hydroxytryptamine, 5HT) is believed to play a role in vasospasm and increased platelet aggregability that in turn could contribute to atherosclerosis. The present study was designed to evaluate a possible participation of serotonin in the development of vascular complications in diabetes mellitus. Whole blood and plasma serotonin, the platelet uptake and release of the amine and serotonin- induced platelet aggregation were studied in 32 patients with Type 2 diabetes. The patients were divided into three groups according to the presence and advancement of retinopathy. Mean levels of blood serotonin content were significantly lower in diabetic patients. The concentration of the amine in the plasma was markedly increased in diabetes. It was correlated with vascular changes of the retina. We established that platelets from diabetic patients took up less serotonin when compared to the control group. Concomitantly enhanced spontaneous release of 5HT from platelets was observed. The platelets of diabetic patients showed increased response to serotonin. There was a relation between serotonin-induced aggregation and the presence of retinopathy. These results suggest that serotonin may be involved in the pathogenesis of diabetic vasculopathy.
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PMID:Blood serotonergic mechanisms in type 2 (non-insulin-dependent) diabetes mellitus. 151 34

Hypertension is a major factor that contributes to the development of the vascular complications of diabetes mellitus, which primarily include atherosclerosis, nephropathy, and retinopathy. The mechanism of the pathophysiological effects of hypertension lies at the cellular level in the blood vessel wall, which intimately involves the function and interaction of the endothelial and vascular smooth muscle cells. Both hypertension and diabetes mellitus alter endothelial cell structure and function. In large and medium size vessels and in the kidney, endothelial dysfunction leads to enhanced growth and vasoconstriction of vascular smooth muscle cells and mesangial cells, respectively. These changes in the cells of smooth muscle lineage play a key role in the development of both atherosclerosis and glomerulosclerosis. In diabetic retinopathy, damage and altered growth of retinal capillary endothelial cells is the major pathophysiological insult leading to proliferative lesions of the retina. Thus, the endothelium emerges as a key target organ of damage in diabetes mellitus; this damage is enhanced in the presence of hypertension. An overall approach to the understanding and treatment of diabetes mellitus and its complications will be to elucidate the mechanisms of vascular disease and endothelial cell dysfunction that occur in the setting of hypertension and diabetes.
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PMID:Hypertension, the endothelial cell, and the vascular complications of diabetes mellitus. 163 68

We have examined thrombin-induced metabolism of phosphoinositides in the platelets from fifteen NIDDM (non-insulin-dependent diabetes mellitus) patients and fifteen healthy subjects (control). The diabetic patients were divided into two groups. One group (group I) had diabetic retinopathy (microangiopathy) and the other group (group II) had atherosclerosis of great vessels (macroangiopathy). In platelets incubated with [32P] orthophosphate for 80 min, the incorporation of 32P radioactivity into phosphatidylinositol (PI), phosphatidylinositol 4-monophosphate (PIP) and phosphatidylinositol 4,5-bisphosphate (PIP2) was significantly lower in the group II than in the control. The addition of thrombin induced a marked decrease in PIP2 radioactivity at 10 sec in platelets from group I compared with that from the control. These results suggest that the breakdown of polyphosphoinositides is increased in platelets from diabetic subjects with retinopathy, and also that the formation of polyphosphoinositides is decreased in the platelets from diabetic subjects with macroangiopathy.
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PMID:Thrombin-induced breakdown of phosphoinositides in platelets from patients with NIDDM. 165 98

Diabetes mellitus is associated with significant morbidity and mortality caused by the micro- and macro-vascular complications that all too frequently develop during the lifetime of the diabetic patient. In attempts to treat the complications of diabetes, several different treatment strategies have been investigated. The role of tight blood glucose control in the treatment of diabetic vascular complications has recently been challenged, as the existing data in support of this mode of therapy are currently inconclusive. Perhaps more effective in preventing many of the vascular complications is the rigorous treatment of hypertension that frequently accompanies diabetes mellitus. Epidemiological studies have demonstrated that the presence of hypertension significantly contributes to the development and progression of diabetic nephropathy, retinopathy, cardiovascular disease, and possibly neuropathy. Preliminary clinical studies demonstrate that the progression of diabetic renal disease can be slowed by vigorous antihypertensive therapy. Among the various antihypertensive agents used to treat the hypertension associated with diabetes mellitus, calcium channel blockers are emerging as one of the agents of first choice. This is because of their very low side effect profile and their absence of detrimental effects on serum lipid levels and glucose tolerance. Calcium channel blockers may be of additional potential benefit to the diabetic patient by slowing the progression of atherosclerosis, reversing the intracellular calcium defects that may contribute to the pathogenesis of diabetic cardiomyopathy, and protecting against the progression of chronic renal disease.
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PMID:The future of calcium channel blocker therapy in diabetes mellitus. 172 50


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