摘要:

Some or most of the turnover of lipoprotein lipase (LPL) occurs by dissociation from vascular endothelial sites in extrahepatic tissues and further degradation in the liver. Heparin greatly enhances this dissociation and delays but does not abolish uptake in the liver, raising the possibility that heparin could lead to accelerated catabolism of functional LPL. To investigate this, we determined time curves for heparin (anti-factor Xa activity) and for LPL and hepatic lipase after injection in rats of two doses of conventional unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH). The high dose (250 U/kg) of both heparins resulted in similar initial levels of LPL activity in plasma, but at 30 minutes the activity with LMWH had declined by more than 80%, whereas with UFH it remained essentially unchanged during this time. In contrast, time curves for heparin activity in blood were similar for the two heparins. The low dose (50 U/kg) led to lower initial levels of LPL activity with LMWH in spite of slower elimination of heparin activity from the blood. These results agree with previous studies that indicate that LMWH has a similar ability as UFH to release LPL, but a lesser ability to delay its removal by the liver. Only slight differences were noted in the time curves for hepatic lipase with the two heparins. To assess the possible depletion of the Upases, we administered a second large dose of conventional heparin. One hour after the first injection, the second injection resulted in lower plasma LPL activities in all four groups. This depletion of releasable LPL was more pronounced with high-dose LMWH (49% of that in saline-treated controls versus about 60% in the other groups). The LPL activity released by the second injection remained significantly depressed with low-dose LMWH and the high dose of either heparin at 4 hours, but had returned to normal after 24 hours. By contrast, no depletion of hepatic lipase activity could be shown at any time. The results showed that release of LPL into the circulating blood is followed by a period during which time the stores of functional LPL are depleted. This occurs with both UFH and LMWH; the difference between the two heparins lies more in the kinetics of the LPL removal process than in its ultimate result.

ISSN:1049-8834    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Chylomicrons labeled in vivo with [14C] trig!ycerides and [3H] retinyl esters were injected in rats at a series of times after administration of conventional unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), or saline. In saline controls the clearance of both chylomicron triglycerides and retinyl esters seemed to follow exponential courses, with half-lives of about 5 and 10 minutes, respectively. Five minutes after administration of LMWH or UFH, the triglyceride clearance rates were dramatically increased and were associated with an increased appearance of the radiolabel in circulating free fatty acids (FFAs). The clearance of [3H] retinol radioactivity, ie, chylomicron particles, was also enhanced 5 minutes after heparin injection. From 75% to 90% disappeared from the circulation within the first 5 minutes. Their continued disappearance was much slower, with a slope similar to that of the saline-treated rats. Hence, it was as if a new, rapid exponent had been added to the disappearance curve that accounted for most of the particle clearance. Injection of chylomicrons 1 hour after the heparins resulted in substantially slower clearance compared with saline-treated controls of both triglyceride and retinol radioactivity in rats given a high dose of LMWH or a low dose of either heparin. Appearance of label in plasma FFAs was also decreased, suggesting that impeded Iipoiysis was responsible, at least in part, for the impeded chylomicron clearance. Four and 24 hours after heparin injection all studied parameters of chylomicron clearance had returned to normal. These data showed that the response of lipoprotein catabolism to heparin is biphasic: immediately after heparin injection, Iipoiysis and particle removal are greatly accelerated; later, both aspects of chylomicron catabolism are temporarily, but markedly, decreased. (Arterioscler Thromb. 1993;13:1397-1403.

ISSN:1049-8834    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

B-mode ultrasound is increasingly used in clinical research to study the atherosclerotic process in the carotid arteries. The present investigation evaluated the feasibility of measuring intima-media thickness in the common femoral artery and assessed whether such measurement might provide further information on the extent of the atherosclerotic process in patients with familial hypercholesterolemia. A further aim was to study the relationship between the intima-media thickness of the common carotid artery and the occurrence of plaque in the carotid and femoral arteries. The results showed an increased intima-media thickness in the far wall of the common femoral artery in patients with familial hypercholesterolemia compared with the control subjects (p<.01). The results also showed a clear relationship between the thickness of the intima-media complex in the common carotid artery and the prevalence of plaque in the carotid and femoral arteries. This may be interpreted as an indication that an increase in intima-media thickness in the common carotid artery at least partly expresses a generalized atherosclerotic process. The atherosclerotic changes appeared to be more advanced in the femoral artery compared with the carotid artery. In future studies, therefore, valuable information on different stages of atherosclerotic changes may be achieved by combining information from B-mode recordings from both the carotid and femoral arteries. (Arteriosder Thromb. 1993;13:1404-1411.

ISSN:1049-8834    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

A case-control comparison within the framework of the prospective, multidisciplinary PLAT Study was performed to assess whether altered baseline fibrinolytic variables were associated with an elevated risk of ischemic thrombotic events in patients with documented coronary, cerebral, and/or peripheral atherosclerotic disease. Fibrinogen, D-dimer, tissue plasminogen activator (t-PA) antigen, and fibrinolytic activity before and after venous stasis (A=difference between the two values), t-PA inhibitor, and lipid levels in 60 atherosclerotic patients with a thrombotic event during the first year of follow-up were compared with those in 94 atherosclerotic patients without such events, who were matched for age, sex, and diagnosis at enrollment. Events were associated with a higher release of A t-PA antigen (P=.O47), higher D-dimer (P=.O24), and higher t-PA inhibitor (P=.001) levels. A Fibrinolytic activity was correlated inversely with t-PA inhibitor (p<.01) and triglycerides (J*<.05). D-Dimer was also correlated with systolic blood pressure (p<.01). Atherosclerotic patients at higher risk of thrombotic ischemic events are characterized by increased fibrin turnover and impaired fibrinolytic activity due to high t-PA inhibitor levels. This hemostatic disequilibrium may participate with conventional risk factors such as elevated triglyceride levels and systolic blood pressure in the multifactorial mechanism of ischemic sequelae in patients with preexisting vascular atherothrombotic disease.

ISSN:1049-8834    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

The effects of dietary fat saturation on the metabolism of low-density Iipoprotein (LDL) subtractions were measured in adult male guinea pigs fed semipurified diets containing 15% (wt/wt) corn oil (CO; 58% llnoleic acid), lard (24% palmitic/14% stearic acid), or palm kernel oil (PK; 52% lauric/18% myristic acid). Animals fed the CO diet had lower plasma total cholesterol levels than guinea pigs fed the PK or lard diets (p<.01). Plasma LDL-1 (<f=1.019 to 1.05 g/mL) concentrations were 3.5- and 2.4-fold higher in animals fed the PK diet compared with the CO and lard groups, respectively, while LDL-2 (d=l.OS to 1.09 g/mL) concentrations were not different among groups. For all dietary fat groups LDL-1 had a higher molecular weight and a larger diameter than LDL-2. LDL fractional catabolic rates (FCRs) varied, depending on both the diet and the LDL subtraction. Animals fed the poiyunsaturated CO diet had a more rapid LDL FCR than animals from the other two groups (7><.01). Within the same diet group, LDL-2 exhibited a slower turnover rate than LDL-1 in animals fed the PK diet, while no differences in LDL subtraction FCR were found in the CO and lard groups. Animals fed the PK and lard diets did not exhibit significant modifications in the density distribution of LDL subtractions over a period of 33 hours. In contrast, animals fed the CO diet exhibited a shift of more buoyant to denser LDL particles, suggesting that differences in LDL intravascular processing are mediated by dietary fat saturation. In vitro LDL binding to hepatic membranes confirmed the in vivo data with an increased expression of apolipoprotein B/E receptors (Bm) in animals fed the CO diet (p<.01). Hepatic apolipoprotein B/E receptors exhibited less affinity for LDL-2 in the PK group, a result consistent with the less rapid turnover of LDL-2 in PK-fed animals. The results suggest that dietary fatty acids varying in saturation and composition have distinctive atherogenic potentials. The lowest plasma LDL cholesterol concentrations mediated by CO intake could in part be explained by induced changes in the composition and processing of LDL subtractions, resulting in faster LDL turnover rates in addition to increased expression of hepatic apolipoprotein B/E receptors. Similarly, the hypercholesterolemic effects of the lard and PK diets appear to be related to differences in intravascular processing of LDL subtractions, with no interconversion between LDL-1 and LDL-2 and that is accompanied by decreased expression of hepatic apo B/E receptors. In addition, PK-fed guinea pigs exhibited a decreased apolipoprotein B/E receptor affinity for LDL-2. {ArterioscUr Thromb. 1993;13:1418-1428.

ISSN:1049-8834    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

We compared the plasma lipoprotein cholesterol, triglyceride, apolipoprotein (apo) A-I, apoB, and lipoprotein (a) [Lp(a)] concentrations in a low coronary heart disease (CHD) risk population (n=440) in Taipei with a high CHD risk population (n=428) in Framingham matched for age, sex, and menopausal status. Taipei men had significantly lower low-density lipoprotein cholesterol (LDL-C) (&#151;20 mg/dL, -14%,p<.01) andapoB (-7 mg/dL, -6%,p<.05) levels and significantly higher high-density lipoprotein cholesterol (HDL-C) levels (6 mg/dL, 13%,p<.01) than Framingham men. Taipei women had significantly lower LDL-C (-18 mg/dL, -15%, /><.01) and higher HDL-C (4 mg/dL, 7%,p<.01) levels than Framingham women. Median concentrations and distributions of Lp(a) by sex were similar in Taipei and Framingham. After adjusting for body mass index and smoking status, only differences in total cholesterol and LDL-C levels remained significantly different for both sexes between the two populations (p<.01). Gender differences for lipids within populations were similar. After adjusting for age, body mass index, and smoking status, women in both Taipei and Framingham had significantly lower mean triglyceride, LDL-C, and apoB levels and significantly higher HDL-C and apoA-I levels than men. Postmenopausal women in Taipei had significantly higher mean total cholesterol, LDL-C, HDL-C, apoA-I, apoB, and Lp(a) levels than premenopausal women (P<.05), whereas in Framingham postmenopausal women had significantly higher total cholesterol, triglyceride, LDL-C, and apoB levels than premenopausal women (p<.05). Our data are consistent with the concept that plasma lipoprotein cholesterol levels (especially LDL-C) but not apolipoprotein values explain some of the twofold difference in age-adjusted CHD mortality between these two populations.

ISSN:1049-8834    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Normoglucemic men with intermittent claudication (n=41), mean age of 63 years, and sex-, age-, body mass index-, and smoking habit-matched controls (n=75) were compared for plasma lipoprotein and hemostatic variables. The patients had significantly lower levels of large high-density lipoprotein (HDL) particles (HDLa, HDL$, and HDLjJ and elevated lipoprotein (a) [Lp(a)] concentrations than the control subjects. Of the hemostatic variables, plasminogen activator inhibitor-1 (PAI-1), plasma antiplasmin, plasma fibrinogen, and urine /J-thromboglobulin concentrations were significantly elevated in patients. In intermittent claudication patients Lp(a) correlated significantly with activation of the coagulation system, ie, with the levels of plasma fibrinogen and urine fibrinopeptide A. No correlations between the values for Lp(a) and PAI-1 or plasma a$-antiplasmin were seen. The PAI-1 activity showed significant univariate correlations to the levels of HDL3k, HDL$ (inverse), and very-low-density lipoprotein triglycerides, of which the positive correlation to HDL}, persisted in multivariate analysis (r- M,p<.001). Independent characteristics for intermittent claudication estimated by multiple regression analysis were PAI-1, plasma fibrinogen, and HDL,., with a combinedR1of 36. The intermittent claudication subgroup that was being treated with /3-blockers/thiazides had a higher frequency of coronary heart disease compared with the other patients. In addition, the patients taking 0-blockers/ thiazides had elevated triglyceride concentrations, lower HDL cholesterol with a size shift toward smaller particles, and a tendency toward raised PAI-1 and plasma a,-antiplasmin levels compared with the patient group that did not take these medications.

ISSN:1049-8834    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

The replicative activity and the differentiation features of aortic smooth muscle cells (SMCs) cultured as whole populations or clones from newborn (4-day-old), young adult (6-week-old), and old (18-month-old) rats were studied by means of cell counting, [3H]thymidine incorporation, and measurement of the expression of cytoskeletal proteins and mRNAs. In whole populations at the fifth passage, replicative activity increased and differentiation features (ie, expression of o-smooth muscle actin, desmin, and smooth muscle myosin heavy chains) decreased with increasing age of the donor animal. SMC clones derived from newborn or young adult rats showed more differentiated cytoskeletal features than their parental populations; however, most SMC clones from old rats showed differentiated features similar to those observed in their parental populations. Our results suggest that (1) SMCs of the rat aortic media behave as a heterogeneous population; (2) cultured whole SMC populations behave differently from clones as far as their replicative activity and differentiation features are concerned; and (3) SMCs derived from old rats, whether grown as whole populations or as clones, dedifferentiate more substantially and replicate more actively than corresponding cultures from newborn or young adult rats when submitted to the same amount of serum growth factors; these differences may play a role in arterial development as well as in the formation and evolution of the atheromatous plaque.

ISSN:1049-8834    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Apolipoprotein (apo) E polymorphism was examined in a population of Italian blood donors. A significantly reduced frequency of the eX allele was observed in comparison to a combined Caucasian population. Apo E polymorphism was also associated with significant differences in plasma lipid and lipoprotein levels. Notably, total and low-density lipoprotein cholesterol as well as triglycerides were increased, whereas high-density lipoprotein cholesterol was decreased in carriers of the E4 isoform. This is the first report of a significantly lower frequency of the apo E4 isoform in a European population. The reduced occurrence of an apo E isoform, which is associated with a more atherogenic lipid/lipoprotein profile, may be a contributory factor to the relatively lower incidence of cardiovascular disease in the Italian population.

ISSN:1049-8834    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Two common founder-related gene mutations that affect the low-density lipoprotein receptor (LDLR) are responsible for &#151;80% of familial hypercholesterolemia (FH) in South African Afrikaners. The FH Afrikaner-1 (FHl) mutation (Asp$&#151;»Glu) in exon 4 results in defective receptors with =20% of normal activity, whereas the FH Afrikaner-2 (FH2) mutation (VaUog-$Met) in exon 9 completely abolishes LDLR activity (<2% normal activity). We analyzed the contribution of these mutations and other factors on the variation of hypercholesterolemia and clinical features in Afrikaner FH heterozygotes. The type of FH mutation, plasma triglyceride levels, and age of patients each contributed significantly to the variation in hypercholesterolemia, whereas smoking status, high-density lipoprotein cholesterol levels, and gender had no influence. Although all FH heterozygotes had frank hypercholesterolemia, patients with the FHl mutation had significantly lower cholesterol levels than those with the FH2 mutation. FHl heterozygotes also tended to have milder clinical features. The differences between the two FH groups could not be explained by a difference in the common apolipoprotein E variants. This study demonstrates that mutational heterogeneity in the LDLR gene influences the phenotypic expression of heterozygous FH.

ISSN:1049-8834    

出版商:OVID    

年代:1993

数据来源: OVID