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)

We evaluated the effect of a low level of hyperlipidemia and the effects of in vitro exposure to atherogenic lipoproteins (LDL, VLDL) on the vascular responsiveness of isolated porcine coronary arteries. Firstly we studied the change in vascular responsiveness induced by feeding a cholesterol-rich diet to pigs for 4 and 9 weeks (C4 and C9 pigs). The serum cholesterol level in pigs fed a cholesterol-rich diet reached 218.5 +/- 32.9 mg/dl compared with 85.5 +/- 8.4 mg/dl in the controls. Segments of the left descending coronary artery were examined. The contraction induced by KCl or prostaglandin F2 alpha was not altered significantly by hypercholesterolemia nor was the relaxation induced by the Ca2+ ionophore, A23187, or by nitroglycerin. Endothelium-dependent relaxation (EDR) evoked by high, but not low, concentrations of bradykinin was reduced in the C4 pigs as compared with those in normal animals. EDRs evoked by bradykinin, substance P, and serotonin were significantly reduced in C9 pigs. Histologically, as observed by light and electron microscopy, fatty changes or intimal thickenings were not seen in the coronary arteries of the C4 pigs. Minimal changes (intimal thickening and fragmentation of internal elastic lamina) were observed only in parts of arteries of the C9 pigs. Secondly, the direct effects of LDL and VLDL on vascular responsiveness were studied. Although preincubation with LDL inhibited the EDR caused by exposure to bradykinin and A23187 in the coronary arteries of normal and cholesterol-fed pigs, preincubation with LDL inhibited the arterial relaxation induced by exposure to substance P or serotonin in both the C4 and the C9 pigs, but not in the control animals. The degree of inhibition was especially marked in the C9 pigs. The inhibitory effect of VLDL on EDR was weaker than that of LDL. Indomethacin (5 microM) did not alter this inhibitory effect of lipoproteins. Neither LDL nor VLDL had any effect on the vascular relaxation induced by nitroglycerin. These results are consistent with the idea that endothelium-dependent arterial relaxation is attenuated even at the very early stage of cholesterol-induced atherosclerosis. Atherogenic lipoproteins may further impair the decreased EDR in the arteries of hyperlipidemic pigs by two factors: one released on stimulation with bradykinin and the calcium ionophore A23187, the other released on stimulation with substance P and serotonin.
 ...
PMID:Low level hyperlipidemia impairs endothelium-dependent relaxation of porcine coronary arteries by two mechanisms. Functional change in endothelium and impairment of endothelium-dependent relaxation by two mediators. 171 35

We examined the effects of a low pathophysiological level of hyperlipidemia and atherogenic lipoprotein (LDL) on the vascular responsiveness of isolated pig coronary arteries. Firstly, we studied the change of vascular responsiveness after feeding a cholesterol-rich diet to pigs for 4 or 9 weeks. Serum cholesterol level in pigs fed with the cholesterol-rich diet reached 218.5 +/- 32.9 mg/dl compared with 85.5 +/- 8.4 mg/dl in controls. Segments of the arteries were mounted in organ chambers for isometric tension recording. Contraction caused by KCl or prostaglandin F2 alpha was not altered significantly by hypercholesterolemia. Relaxation in response to Ca2+ ionophore A23187 or nitroglycerin was not altered significantly by hypercholesterolemia. Relaxation in response to Ca2+ ionophore A23187 or nitroglycerin was not altered. Endothelium-dependent relaxation evoked by high but not low concentrations of bradykinin and substance P were reduced in pigs fed with the cholesterol-rich diet for 4 weeks as compared with those in normal pigs. Those evoked by bradykinin, substance P, and serotonin were significantly reduced in pigs fed with the cholesterol-rich diet for 9 weeks. Histologically, the fatty changes or intimal thickening were not so evident in coronary arteries of pigs fed for 4 weeks with the cholesterol-rich diet, but only minimal changes were observed in those fed with the diet for 9 weeks by light or electron microscopy. Secondly, the direct effects of LDL on the vascular responsiveness were examined.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Hyperlipidemia impairs vascular endothelium-dependent relaxation in pig coronary arteries]. 223 15

The multisystem involvement in acute pancreatitis (AP) is a reflection of the pancreatic gland's capacity to produce a number of potent vasoactive peptides, hormones, and enzymes. The various prognostic criteria are early evaluations of these metabolic derangements. The pathogenesis of hypocalcemia, long recognized as an indicator of severity of AP, is multifactorial. Imbalances of parathyroid hormone (PTH)-calcitonin, the interactions of glucagon, gastrin and other pancreatic hormones with PTH-calcitonin, the role of free fatty acids in binding serum calcium with albumin, and the translocation of calcium ion in muscles and liver, have been recently described but remain conflicting theories. Yet, the time-honored theory of calcium-soap formation enjoys wide acceptance. Hyperglycemia, hypoglycemia, and occasional ketoacidosis in acute pancreatitis have been studied thoroughly. The complex cause-and-effect relationship between hyperlipidemia with acute pancreatitis needs further study. The coagulation abnormalities seem to be initiated by activated trypsin, and their role in microvascular coagulation appears to form a unifying hypothesis for major organ dysfunction, but this requires further investigation. Adult respiratory distress syndrome may be the result of active enzymes that digest pulmonary surfactant and/or microvascular thrombosis. The depression of cardiac function and shock are suspected to be secondary to vasoactive peptides such as bradykinin, or myocardial depressant factor, whose structure has yet to be elucidated. The renin-angiotensin alterations and renal complications in acute pancreatitis have received scant attention in the literature. The onset of moderate visual disturbances, or even blindness, in a patient with acute pancreatitis as a result of retinal vessel thrombosis is fortunately uncommon. Rare but interesting are the manifestations such as subcutaneous fat necrosis, arthralgia, and pancreatic encephalopathy. Despite the extensive literature on the complexities of the pathogenesis of complications of acute pancreatitis, there have been very few advances in the prevention and management of specific complications. It is hoped that further work on modification of enzymatic disturbances induced in acute pancreatitis will result in its effective treatment and prevention of serious complications.
 ...
PMID:Systemic complications of acute pancreatitis. 328

The degree of hyperlipidemia, hyperthyrosinemia, hyperserotoninemia and enhanced release of bradykinin from kininogen in patients with chronic recurrent pancreatitis was found to be decreased upon the attainment of a clinical remission. In patients with more considerable and more stable metabolic disorders, the incidence of exacerbations and the rate of progression of pancreatic, enzyme-secretory deficiency appeared, according to the data of a 8-year follow up, greater than in those with lesser degree and resistance of metabolic shifts.
 ...
PMID:[Clinical significance of various metabolic disorders in patients with chronic pancreatitis]. 652 93

Hyperlipidemia contributes to the development of intimal hyperplasia and subsequent accelerated atherosclerosis in vein bypass grafts. This study examines the effect of dietary supplementation with L-arginine on the development of intimal hyperplasia and the vasomotor function of vein grafts in hypercholesterolemic animals. Thirty male New Zealand White rabbits had a right carotid vein bypass graft and were sacrificed at 28 days postoperatively. Twenty animals received a 1% cholesterol diet for 4 weeks prior to surgery and this diet was continued until harvest. Of these, 10 also received L-arginine (2.25%, 2 g/kg, p.o.) 7 days preoperatively and thereafter until harvest. The last 10 animals were controls. Vein grafts were harvested either for morphology or for in vitro isometric tension studies. Cumulative dose-response curves to norepinephrine, serotonin, and bradykinin were recorded, and following norepinephrine precontraction, relaxation to acetylcholine and sodium nitroprusside were determined. After in situ pressure fixation, intimal thicknesses of the vein grafts were measured by videomorphometry. The addition of L-arginine doubled the serum arginine concentrations. Intimal hyperplasia of both groups of hypercholesterolemic vein grafts contained foam cells and lipid-laden endothelial and smooth muscle cells. There was a 24% reduction in the intimal thickness of vein graft intimal hyperplasia in the L-arginine group compared to that in the hypercholesterolemia group (P < 0.05). All hypercholesterolemic vein grafts were two-fold thicker than in the control group. L-arginine supplementation resulted in the preservation of acetylcholine-mediated relaxation but did not change hypercholesterolemia-induced contractile agonist supersensitivity.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Control of accelerated vein graft atheroma with the nitric oxide precursor: L-arginine. 763 Jan 34

The goals of rational antihypertensive medication should embrace the alleviation of atherosclerosis, the clinical consequences of which pose a major health problem and hence socio-economic concern for industrialized countries. Angiotensin converting enzyme (ACE) inhibitors are endowed with pharmacodynamic features which may help to attain this aim. Various animal experiments with cholesterol-fed rabbits, pigs and monkeys, as well as with rabbits with inherent disorder of lipid metabolism (WHHL-rabbit), demonstrated endothelial protection against loss of function due to hyperlipidemia and attenuation of lipid deposition in conduit blood vessels with ACE-inhibition. The alleviation of progressive atherosclerosis, which is a common feature of restenosis development following angioplasty, was shown in hypercholesterolemic rabbits and normal rats, but did not occur in clinically more relevant porcine models nor in large clinical trials. Circumstantial evidence from miscellaneous experiments is in line with the view that it is enhancement of bradykinin activity which causes the endothelial protection against the consequences of hypercholesterolemia. Furthermore, loss of relaxation of coronary resistance vessels without overt atherosclerosis despite hypercholesterolemia can be restored by augmentation of the EDRF-pathway as has been demonstrated with ramiprilat in vitro. This is being substantiated in preliminary clinical reports with different ACE-inhibitors. The possible association between improvement in both insulin sensitivity and endothelial function requires further investigation. The critical analysis of present experimental findings on a beneficial influence on both the spontaneous and the progressive development of atherosclerosis indicates ACE-inhibition to be more likely to preserve or restore the function of an intact endothelium than to interfere with the complex reaction occurring after injury of an already affected blood vessel.
 ...
PMID:[ACE inhibition and atherosclerosis in the animal model]. 785 76

By the mediation of receptors in the endothelium, bradykinin, histamine, and thrombin--besides platelet-derived substances such as adenosine diphosphate and triphosphate (ADP, ATP) and serotonin--play an essential physiological role in the activation of the protective metabolic process in the endothelium, which is so important to vessel dilatation. The described process is attenuated by pathologic conditions such as e.g. hyperlipidaemia and hypertension. Furthermore, in the case of experimental hypertension, the production of contractile endothelial factors, which weaken the effect of the vasodilatory endothelial factors, is likely to increase. Obviously, an efficient antihypertensive therapy prevents from this endothelial dysfunction, at least in animal experiments.
 ...
PMID:[Receptor-mediated endothelial vascular regulation (brief report)]. 818 16

Coronary arteries are regulated by neuronal mechanisms, hormones and paracrine mediators. The importance of endothelium-dependent mechanisms has recently been recognized. The endothelium responds to mechanical and chemical signals from the blood by releasing mediators that modulate vascular tone and structure, platelet function, coagulation and monocyte adhesion. Important relaxing factors are nitric oxide, prostacyclin and a putative hyperpolarizing factor. Nitric oxide also inhibits smooth muscle proliferation and, together with prostacyclin, platelet function. Bradykinin-induced nitric oxide production is reduced by angiotensin-converting enzyme. Endothelin-1, thromboxane A2 and prostaglandin H2 are contracting factors. Thromboxane A2 and prostaglandin H2 activate platelets, while endothelin has no direct platelet effects, but causes smooth muscle proliferation. In hypercholestermia, endothelium-dependent relaxation is impaired and contraction as well as adhesion of monocytes and platelets enhanced. Pharmacological correction of hyperlipidemia by statins also improves or normalizes endothelial dysfunction in patients. Angiotensin-converting enzyme inhibitors have similar effects.
 ...
PMID:Lipids and endothelial function: effects of lipid-lowering and other therapeutic interventions. 888 99

New evidence suggests an interaction between hyperlipidemia, activation of the renin-angiotensin system, and atherosclerotic disease. In patients with atherosclerosis and hyperlipidemia, coronary endothelial dysfunction is usually diffuse and affects vasomotor tone, platelet activity, thrombosis, fibrinolysis, and regulation of inflammatory cells. Angiotensin II, an important oxidant, alters the binding of low-density-lipoprotein (LDL) cholesterol to its receptors and increases endothelial uptake of LDL. Endothelial dysfunction is worsened by the suppression of nitric oxide production and/or release via angiotensin II-associated degradation of bradykinin and oxygen free radical production, resulting in inadequate vasorelaxation. Therapy with angiotensin-converting enzyme (ACE) inhibitors appears to eliminate these untoward effects and may ameliorate the tendency for myocardial infarction associated with elevated plasma levels of angiotensin II. Although the role of ACE inhibitors in the prevention and/or treatment of coronary artery disease in patients without left ventricular dysfunction remains to be established, the capacity of ACE inhibition to correct endothelial dysfunction offers promise. The ability of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors to improve endothelial function, prevent the progression of coronary atherosclerosis, reduce the incidence of ischemic events, and improve survival is well known. Potentially, ACE inhibitors may have an additive or synergistic effect on the development of atherosclerosis and the clinical consequences of this disease when used in combination therapy with lipid-lowering strategies.
 ...
PMID:The potential use of angiotensin-converting enzyme inhibitors in patients with hyperlipidemia. 912 18

Atherosclerosis and its consequences account for most of the morbidity and mortality in Western countries. It is a disease of the intima and primarily involves four cell types, i.e., endothelial and vascular smooth muscle cells, monocytes and platelets. In recent years, knowledge on the cellular and molecular mechanisms of these cells and their alterations by cardiovascular risk factors and in atherosclerosis has greatly expanded. In particular, it has become clear that endothelial cells play a crucial role in the regulation of platelet function, coagulation, and vascular tone and structure. Interestingly, endothelial dysfunction occurs early, particularly if cardiovascular risk factors such as hyperlipidemia, hypertension and diabetes are present. This could lead to adhesion of circulating platelets and monocytes and increased accumulation of lipids in the intima, as well as increased contraction, migration and proliferation of vascular smooth muscle cells. One of the enzymes with a key role in vascular homeostasis is angiotensin I converting enzyme (ACE). ACE is located on the endothelial cell membrane and is responsible for the conversion of angiotensin I into angiotensin II, as well as for the breakdown of bradykinin. While the antihypertensive effect of ACE inhibitors probably contributes to their antiatherogenic effects, other mechanisms are likely to be of greater importance. These direct antiatherogenic effects attributable to ACE inhibition are related to their vasculoprotective properties, including antiproliferative and antimitogenic activity, effects on endothelial function, protection against plaque rupture, antithrombotic effects, and possible antioxidant properties. There is overwhelming evidence to demonstrate the beneficial effects of long-term ACE inhibitor treatment in heart failure, acutely for suspected myocardial infarction (MI), and following MI in patients with left ventricular dysfunction. Hypercholesterolemia is a health risk, and epidemiological studies have shown a line between total cholesterol levels and the risk of cardiac events. Studies have shown that lowering the levels of total and low-density lipoprotein cholesterol using HMG-CoA reductase inhibitors can result in a decrease in cardiac morbidity and mortality. Angiographic studies of coronary arteries have demonstrated a disparity between the decrease in cardiac events and the extent of regression of coronary artery lesions. Mechanisms other than the regression of coronary stenosis may therefore be important in the beneficial effect of cholesterol lowering. It may be of major importance that lipid-lowering therapy is associated with improved endothelial function and decreased platelet activity. Thus, both ACE inhibitors and HMG-CoA reductase inhibitors have vasculoprotective properties which may explain their beneficial effects on cardiovascular morbidity and mortality.
 ...
PMID:[Pharmacotherapy of arteriosclerosis and its complications. Effect of ACE inhibitors and HMG-CoA-reductase inhibitors]. 919 90


1 2 3 Next >>