Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hyperlipidemia and hypertension play important roles in the pathogenesis of atherosclerosis. To investigate the underlying intracellular mechanisms, we studied the effect of various concentrations of low density lipoprotein from normolipidemic subjects on concentrations of free intracellular calcium, intracellular pH, DNA synthesis, and vascular tone in vascular smooth muscle cells and rings from rat aortas. Low density lipoprotein in the range of 1-15 micrograms/ml induced a dose-dependent increase of concentration of free intracellular calcium and a biphasic change of the intracellular pH. Similar concentrations of low density lipoprotein led to an enhanced DNA synthesis. Furthermore, cumulative addition of 1-15 micrograms/ml low density lipoprotein produced a dose-dependent increase in contractile tension of thoracic aortic rings from rats. The maximal low density lipoprotein-induced contractile response was approximately 70% of that induced by 40 mM KCl. These findings indicate that low concentrations of low density lipoprotein occurring, for example, in the extravascular fluid might contribute to the pathogenesis of cardiovascular diseases by enhancing cell proliferation and vasoconstriction by changing intracellular calcium and intracellular pH.
 ...
PMID:Novel cellular activities for low density lipoprotein in vascular smooth muscle cells. 235 25

The influence of experimentally induced hyperlipidemia and aging on the development of pulmonary foam cells (PFCs) was examined in Fischer 344 rats. The male and female rats were administered orally with cholesterol at a dosage level of 1000 mg/kg/day for 30 days from 6 to 10 weeks or from 33 to 37 weeks of age. The control rats received the vehicle only in the same manner. Plasma levels of total cholesterol, phospholipid, triglyceride (TG), beta-lipoprotein (beta-LP) and calcium in both control and cholesterol-administered groups were higher at 37 weeks than at 10 weeks of age. Plasma beta-LP and TG levels in the treated groups were significantly higher or tended to be higher than those of the controls at 10 and 37 weeks of age. Males of the treated group showed the highest level of beta-LP at 37 weeks of age, positively correlated with the highest incidence of PFCs. PFCs developed singly or in a small cluster in peribronchial and subpleural regions. PFCs had an abundant cytoplasm filled with many fine vacuoles containing neutral lipid and cholesterol. PFCs stained with PAS and reacted immunohistochemically with both anti-rat monocytes/macrophages monoclonal antibody and anti-lysozyme antibody. Moderately swollen macrophages with a foamy appearance were detected in perivascular connective tissues of the lungs and they were considered to represent an initial stage of the development of PFCs. These observations suggest that hyperlipidemic conditions, particularly hyper beta-lipoproteinemia, resulting from cholesterol administration or aging may be involved in the development of PFCs in rats.
 ...
PMID:Influence of cholesterol administration and aging on the development of pulmonary foam cells in F344 rats. 260 22

Experimental research using in vitro and in vivo models of vascular injury have delineated several common mechanisms that characterize the arterial damage in diseases such as atherosclerosis and hypertension. Changes in endothelial permeability, smooth muscle cell proliferation, and accumulation of connective tissue matrix are major common mechanisms. Chronic hyperlipidemia is a major determinant of the proliferative arterial lesions in atherogenic models. Calcium antagonists of very diverse structure and function have been shown to have antiatherogenic potential in several animal model systems of arterial injury. Calcium channel-blockers of several chemical classes have been demonstrated to alter endothelial function, intimal smooth muscle proliferation, and lipid accumulation in the arterial wall. Cell culture model systems have elucidated several potential mechanisms that may contribute to the antiatherogenic potential of the calcium channel-blockers. These activities may in part involve protection of arterial cells from calcium overload via inhibition of calcium flux across voltage-regulated ion channels. However, other activities of these drugs, such as inhibition of cholesterol esterification and matrix protein formation, appear to function independently of calcium flux. A hypothesis is presented that lipophilic calcium channel-blockers are accumulated in cell membranes and perturb metabolic function as a result of altering local membrane structure.
 ...
PMID:Protective action of calcium channel antagonists in atherogenesis and experimental vascular injury. 264 20

Various endocrine and metabolic disturbances associated with long standing uremia persist after kidney transplantation or arise from the use of immunosuppressive drugs. Hyperlipidemia for long time being implicated as the cause of corticosteroids is also observed in renal transplant recipients treated with cyclosporin A monotherapy. After conversion from cyclosporin to azathioprine serum cholesterol and triglyceride concentration fall, and elevation of LDL-cholesterol may also be reversed. There is a tendency for higher HDL-cholesterol in azathioprine and prednisolone treated transplant patients. Those patients who are at risk for clinically significant cholesterol elevations can be predicted by their pretransplant lipid levels, specifically the LDL-fraction. Risk-benefit ratio of conversion and of treatment with lipid-lowering drugs, especially with lovastatin, should be carefully examined, also in view of glucose intolerance. Higher incidence of diabetes mellitus requiring insulin therapy in cyclosporin treated transplant recipients has been reported. Cyclosporin may cause toxic effects on pancreatic beta-cells resulting in inhibition of insulin secretion. High doses of cyclosporin induce inhibition of glycogen synthesis in rat liver. Glucose intolerance is reversible after reduction of cyclosporin dose or conversion to azathioprine. Therefore glucose metabolism in kidney transplant recipients treated with cyclosporin should be carefully followed. Immunosuppressive therapy may affect reproductive function, arachidonate metabolism and renin-angiotensin-aldosterone system as well as posttransplant calcium and phosphate metabolism. Endocrine and metabolic abnormalities are associated with long standing uremia. After successful kidney transplantation several observations are normalized but further complications arise from the use of immunosuppressive drugs. The present paper reviews various endocrine and metabolic disturbances described following renal transplantation.
 ...
PMID:Endocrine and metabolic abnormalities following kidney transplantation. 268 69

Experimental and clinical evidence points to the existence of a cardiomyopathy associated with diabetes mellitus that is not due to coronary atherosclerosis. The condition is characterized by distinct clinical presentations and physiologic and biochemical abnormalities. Potential mechanisms for the development of diabetic cardiomyopathy are complex but are probably associated, in part, with hyperglycemia and hyperlipidemia. Primary hypertension is also associated with the development of myocardial abnormalities. Many of these changes are similar to those seen in diabetic cardiomyopathy. It is now clear that the co-existence of hypertension and diabetes mellitus produces a more severe cardiomyopathy than that produced by hypertension or diabetes alone. Potential mechanisms for interaction are numerous. Treatment of hypertension in diabetic patients must be targeted to more specific needs. Antihypertensive drugs should not worsen cardiac risk factors or glucose control and should have favorable effects on left ventricular function. The calcium antagonists and angiotensin-converting enzyme inhibitors have pharmacologic profiles that make them attractive as monotherapy for diabetic patients.
 ...
PMID:Myocardial disease in hypertensive-diabetic patients. 268 10

1. The effects of isoproterenol (ISO) on the ultrastructure of hearts from 10-week alloxan diabetic rabbits were examined. 2. Following alloxan injection, all rabbits developed severe hyperglycemia, hyperlipidemia and hypoinsulinemia. 3. Injection of ISO induced marked alterations in both control and diabetic rabbit hearts including accumulation of lipid and swelling of sarcoplasmic reticulum. 4. Myofibrils in both groups of animals were dispersed and appeared as a homogeneous mass with poorly defined Z-bands. 5. The most marked effect of ISO treatment in both groups of animals was damage to mitochondria. Mitochondria were extensively damaged and showed partial or complete disruption of their cristae network. 6. Glycogen granules were few in number or not detectable in both groups of animals. 7. The diabetic animals treated with ISO showed greater clumping and margination of nuclear chromatin, fewer intact mitochondria and a greater number of amorphous dense bodies in and around the mitochondria. 8. The presence of greater sarcolemmal damage in diabetic animals was inferred from the significantly greater accumulation of calcium and decreased magnesium in the myocardium.
 ...
PMID:Isoproterenol-induced ultrastructural alterations in hearts of alloxan-diabetic rabbits. 275 45

Recent clinical trials in hypertension report more deaths due to coronary heart disease in mild hypertensives who received aggressive antihypertensive drug therapy and achieved better blood pressure control. Subset analyses of these trials suggest that diuretic therapy may have contributed to this outcome, possibly through a reduction in serum potassium or an elevation in serum lipids. Because of this, patients with an abnormal pretreatment electrocardiogram, history of myocardial infarction, unstable coronary heart disease, or diuretic-induced hyperlipidemia or hypokalemia unresponsive to management are candidates for alternative antihypertensive agents. A review of the literature suggests that most of the currently available beta-blockers, the alpha 1-antagonist prazosin, the angiotensin-converting enzyme inhibitor captopril, and the vasodilator hydralazine are effective alternatives to thiazide therapy in the initial management of hypertension and are recommended for particular subgroups of patients. Monotherapy with the centrally and peripherally acting sympatholytic agents is not recommended because of the frequent side effects encountered and the inferior hypotensive efficacy reported. Calcium channel blocking agents also appear to be suitable alternatives to thiazides in hypertension, but more experience with these is needed. Alternative pharmacologic agents may be selected on the basis of age, and, to a lesser extent, race.
 ...
PMID:Alternative pharmacologic approaches to the initial management of hypertension. 286 26

Like the liposomes of certain intravenous fat emulsions associated with embolic effects in acutely ill patients, chylomicrons and very low density lipoproteins (VLDL) show calcium-dependent agglutination by C-reactive protein (CRP). It is suggested that non-traumatic fat embolism may be caused by agglutination of chylomicrons and VLDL by high levels of plasma CRP. This mechanism may also cause acute pancreatitis in patients with types I, IV, and V hyperlipidaemia, and avascular necrosis of bone in patients with corticosteroid-induced hyperlipidaemia.
 ...
PMID:Pathogenesis of non-traumatic fat embolism. 289 46

Although we are on steep learning curve as far as the exact relationship between nutrition and disease prevention is concerned, evidence is accumulating on the role of body mass index and mortality, protein deficiency and decreased ability to fight infection, effect of fiber intake on cholesterol and glucose metabolism, hyperlipidemia and atherosclerosis, and inadequate calcium intake in osteoporosis. Screening for nutritional disorders includes identifying those with risk factors of being female, black, poor, or institutionalized. Evidence of weight change, dietary idiosyncracies, nutrient deficiency, and laboratory tests can be helpful. Treatment should be tailored to the individual and be specific for suspected deficiencies. Attention to calories, protein, and calcium are paramount.
 ...
PMID:Health maintenance issues of the elderly. Nutrition. 291 14

There is good epidemiologic evidence that hypertension is associated with a high risk of cardiovascular disease. However, primary intervention trials have failed to demonstrate that a reduction in blood pressure in hypertensive patients reduces morbidity and mortality from cardiac events. Since various antihypertensive drugs adversely affect lipoprotein metabolism, these drugs may increase associated coronary risk and offset the beneficial effects of lowering blood pressure. This article reviews the effects of various antihypertensive drugs on plasma lipids, lipoproteins, and apolipoproteins. They can be summarized as follows: thiazide-type diuretics cause a marked elevation of plasma triglycerides and very low-density lipoprotein (VLDL) and minor increases in total cholesterol and low-density lipoprotein (LDL), but have little effects on high-density lipoprotein (HDL). The nonselective beta-blockers do not significantly affect total cholesterol and LDL, but increase total triglycerides and VLDL and decrease HDL. The changes in plasma lipids and lipoproteins caused by cardioselective beta-blockers and beta-blockers with intrinsic sympathomimetic activity are qualitatively similar but less pronounced. Calcium antagonists and angiotensin-converting enzyme inhibitors appear to have no significant effects on plasma lipids. alpha 1-Inhibitors reduce total triglycerides, total cholesterol, VLDL, and LDL and increase HDL. The possible mechanisms by which antihypertensive drugs affect cellular lipid metabolism (e.g., LDL receptor, lipid synthesis, lipoprotein lipase, lecithin cholesteryl acyltransferase, acylcholesteryl acyltransferase, and cholesteryl ester hydrolase) are described. The clinical significance of changes in blood lipids and cellular lipid metabolism caused by antihypertensive drugs is not yet totally clear. Nevertheless, before antihypertensive drug treatment is initiated, blood lipid levels should be measured to identify preexisting hyperlipidemia.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Effects of antihypertensives on plasma lipids and lipoprotein metabolism. 305 88


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