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)

Low density lipoprotein (LDL) and high density lipoprotein (HDL3) were tested for their ability to induce inositol phospholipid turnover and inositol phosphate production in bovine aortic endothelial cells (BAEC). The production of inositol phosphates following hydrolysis of the phosphoinositides was demonstrated by two methods; release of [3H]inositol phosphates after labelling with [3H]myo-inositol and by a direct binding assay for inositol 1,4,5-trisphosphate (InsP3). Acute exposure to LDL induced InsP3 release at low concentrations of the lipoprotein within the physiological range of LDL in tissues. HDL3 did not cause any release of the inositol phosphates. Pre-incubation of BAEC with HDL3 suppressed bradykinin- and LDL-induced inositol phosphate production in BAEC in a concentration-dependent manner. It is concluded that LDL acutely stimulates phosphoinositide breakdown and that pre-incubation of cells with HDL3 inhibits this effect. The mechanism responsible for these effects remains to be elucidated.
Atherosclerosis 1992 Jan
PMID:The effects of low density lipoprotein and high density lipoprotein on phosphoinositide hydrolysis in bovine aortic endothelial cells. 131 50

Factors involved in the pathogenesis of atherosclerosis, thrombosis and vasoconstriction contribute to the development of coronary heart disease. In a study comparing patients after myocardial infarction with controls, we have explored a possible association between coronary heart disease and a variation found in the gene encoding angiotensin-converting enzyme (ACE). The polymorphism ACE/ID is strongly associated with the level of circulating enzyme. This enzyme plays a key role in the production of angiotensin II and in the catabolism of bradykinin, two peptides involved in the modulation of vascular tone and in the proliferation of smooth muscle cells. Here we report that the DD genotype, which is associated with higher levels of circulating ACE than the ID and II genotypes, is significantly more frequent in patients with myocardial infarction (n = 610) than in controls (n = 733) (P = 0.007), especially among subjects with low body-mass index and low plasma levels of ApoB (P < 0.0001). The ACE/ID polymorphism seems to be a potent risk factor of coronary heart disease in subjects formerly considered to be at low risk according to common criteria.
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PMID:Deletion polymorphism in the gene for angiotensin-converting enzyme is a potent risk factor for myocardial infarction. 132 87

Most of the linkage of atherosclerosis and thrombosis with estrogens is epidemiologic in origin. Although the effects of estrogens on the mechanisms of hemostasis are wide ranging, many are benign; only a few may account for thrombus formation. Platelet function tests have provided extensive but contradictory data, and interpretation is limited because it is uncertain whether a rise in one or more of these parameters is a primary or secondary effect. The most consistent effects of estrogens on coagulation proteins are elevations of fibrinogen; factors II, VII, IX, X, and XII; protein C; and plasminogen. Although these elevations have been attributed to the estrogenic component in oral contraceptives, the progestogen concentration may also influence these increases. Among other coagulation proteins studied, the following are unaffected by oral contraceptive use: factors V, VIII, and XI; prekallikrein; and high-molecular-weight kininogen. In contrast, protein S values are decreased. The plasma concentration of plasmin inhibitor is unchanged, whereas both proteinase inhibitor and macroglobulin are significantly increased by oral contraceptive use. Cl esterase inhibitor is decreased in women taking oral contraceptives and correlates with the increase in Hageman factor. Antithrombin III is one plasma inhibitor for which a decrease in quantity and activity have been associated with a thrombotic tendency in humans. Although data on estrogen-associated changes in the quantity of antithrombin III have been conflicting, the ability of plasma to inhibit factor Xa is significantly reduced in a dose-dependent manner among pre- and postmenopausal estrogen users.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Estrogen-associated thromboembolism. 134 94

Normal New Zealand and Watanabe heritable hyperlipidemic (WHHL) rabbits, about 24 months old, were prepared, under anaesthesia, for recording blood pressure and hindlimb blood flow. Changes in hindlimb vascular resistance were measured after local intra-arterial bolus injection of increasing doses of acetylcholine, bradykinin, serotonin, sodium nitroprusside and phenylephrine. In WHHL rabbits basal hindlimb blood flow was reduced (from 22.6 +/- 3.0 to 12.5 +/- 1.8 ml/min; P less than 0.05) and hindlimb vascular resistance was increased (from 4.6 +/- 0.5 to 8.2 +/- 1.5 mmHg/ml per min; P less than 0.05). No difference was observed in response to acetylcholine, serotonin, sodium nitroprusside and phenylephrine. The only marked alteration found in WHHL rabbits was a clear deficit to bradykinin stimulation. Morphological analysis, using scanning and transmission electron microscopy, indicated a clear damage of the femoral artery, like the presence of atherosclerotic plaques, and an abnormal distribution of patent microvessels in the WHHL muscles of the leg. Peripheral circulation in WHHL rabbits shows some peculiar features, like increased basal vascular resistance and a selective impairment of bradykinin responses. Together with these abnormalities, it seems that responses to various other dilating or contracting agents are normal, suggesting that in this interesting animal model of atherosclerosis the alterations are more specific than in other models.
Atherosclerosis 1992 Mar
PMID:Functional responses of hindlimb circulation in aged normal and WHHL rabbits. 159 96

Kallikrein (Padutin-Depot) was administered to 20 patients with obliterative atherosclerosis of the lower limbs of the II degree (19 patients) and IV degree (1 patient). The drug was given in the daily dose of 40 U i.m. for 28 days. An effect of kallikrein on the distance in intermittent claudication, rate of pain relieve after walking the maximal distance, blood flow in the lower limbs, and on the index of circulating aggregates have been determined. Clinical improvement has been noted after a 4-week therapy with kallikrein. The drug in a single dose of 40 U activates plasma fibrinolytic system for 5 hours and decreases the number of circulating aggregates (2-5 h). The authors explain kallikrein action as the release of endogenous bradykinin, which subsequently releases two epithelial mediators, i.e. PFG1 and EDRF.
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PMID:[Kallikrein in the treatment of patients with obliterative atherosclerosis of the lower limbs and its mechanism of action]. 166 40

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.
Atherosclerosis 1991 Mar
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

Hypertension and hypercholesterolemia predispose to atherosclerosis. Ramipril, known to lower blood pressure, was used to study the effect of converting-enzyme inhibition on impairment of endothelium-derived relaxation and changes in basal cGMP content in rabbits fed an atherogenic diet (0.25% cholesterol). The generation of cGMP in the presence of bradykinin and ramiprilat was studied in vitro in aortic segments from normal untreated rabbits as well as in bovine endothelial cells. The ability to relax in response to acetylcholine was almost abolished in aortic segments from the vehicle-treated rabbits fed the atherogenic diet for 4 months. The basal cGMP content was substantially reduced. Aortic segments from rabbits concomitantly treated with ramipril (0.3 and 3.0 mg/kg/day) for 3 months showed well-preserved relaxation and matching basal cGMP content compared to normal controls. The relaxation was not significantly greater in aortic segments from ramipril-treated rabbits fed the standard diet, but the cGMP content was more than doubled. In vitro studies in aortic segments and in endothelial cells showed that both the ramiprilat and bradykinin concentrations dependently stimulated cGMP formation, which serves as a biochemical marker of nitric oxide or EDRF release. Thus, the observed endothelial protection against hypercholesterolemia by ramipril may be the result of continuously increased cGMP formation due to preserved EDRF release. This is presumably produced by enhanced bradykinin activity through inhibition of degradation by converting-enzyme inhibition with ramipril.
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PMID:Preservation of endothelial function by ramipril in rabbits on a long-term atherogenic diet. 172 17

A sesquiterpenic lactone leucomyzin possessing the anti-inflammatory activity significantly reduces the extensiveness of atherosclerotic lesions of the aortas of the rabbits receiving dietary cholesterol. The drug prevents an increase of permeability of the aorta and microvessels under the influence of cholesterol, bradykinin, ovalbumin and histamine. In addition to the angioprotective action, leucomyzin possesses the hypolipidemic activity in rats with experimental hyperlipidemias and (after prolonged administration) in rabbits with cholesterol atherosclerosis. By its antiatherosclerotic and angioprotective activity leucomyzin is superior to prodectine, by its hypolipidemic action it is comparable with miscleron.
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PMID:[The angioprotector and hypolipemic activity of leukomizin in experimental atherosclerosis]. 191 17

Pertussis toxin, an irreversible inhibitor of some G proteins, inhibits endothelium-dependent relaxations to certain agonists in porcine coronary arteries. In the present study, the effects of the toxin were examined on endothelium-dependent and -independent relaxations of hypercholesterolemic and atherosclerotic porcine coronary arteries to assess the functional state of the endothelial pertussis toxin-sensitive G protein. Male Yorkshire pigs were maintained on either a regular diet (control group, n = 7) or a 2% high-cholesterol diet (cholesterol-fed group, n = 7) for 10 weeks. After the initial 2 weeks of maintenance, animals in both groups underwent balloon catheter removal of the endothelium of the left anterior descending or left circumflex coronary arteries. Endothelium-dependent responses were examined in vitro after 10 weeks of maintenance; at this time, a full lining of endothelial cells in both left coronary arteries was confirmed histologically. In arteries with endothelium of the control group (normal responses), pertussis toxin significantly inhibited the endothelium-dependent relaxations to serotonin, UK14304 (a selective alpha 2-adrenergic receptor agonist), and thrombin but not those to ADP, bradykinin, or the calcium ionophore A23187. In previously denuded arteries of the control group (effects of endothelial regeneration alone) or intact arteries of the cholesterol-fed group (effects of hypercholesterolemia alone), the relaxations to serotonin, UK14304, and thrombin were impaired significantly; those relaxations were impaired further in previously denuded arteries of the cholesterol-fed group (effects of atherosclerosis). The inhibitory effects of pertussis toxin were significantly reduced after endothelial regeneration and in hypercholesterolemia and were almost absent in atherosclerosis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Loss of endothelial pertussis toxin-sensitive G protein function in atherosclerotic porcine coronary arteries. 199 83

The functions of the endothelium and the effects of hypertension, atherosclerosis, and diabetes on the endothelium are reviewed. The endothelium affects vascular tone by releasing vasodilators and modulating the effects of vasoactive substances such as catecholamines, bradykinin, serotonin, and angiotensin II. Relaxation of vascular smooth muscle depends upon a functionally intact endothelium and the release of the endothelium-derived relaxing factor nitric oxide. Endothelial cells also appear to release a hyperpolarizing factor that relaxes smooth muscle through activation of the sodium-potassium pump, and of the endothelium-dependent contracting factors. Similarities are found in the vascular injury resulting from hypertension, atherosclerosis, and diabetes. When these risk factors coexist, they can act synergistically and magnify the vascular injury. The endothelium appears to be one of the major targets for these forms of injury. Future therapeutic strategies will focus on ways to prevent, arrest, or reverse endothelial injury.
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PMID:Hypertension, endothelium, and cardiovascular risk factors. 199 9


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