摘要:

Unsaturated fatty acids are thought to prevent thrombotic and arteriosclerotic disease, whereas saturated fatty acids are thought to increase the incidence of these disorders. However, the effects of these diets on megakaryocytes and platelets are not welll understood. We compared the effects of diets enriched with 8.4% olive oil, 8.4% hydrogenated palm oil, or 10.2% to-3 fatty acid ethyl esters on guinea pig megakaryocytes and platelets. In plasma, changes in fatty acid composition reflected the composition of each diet. However, in platelets and megakaryocyi:es, hydrogenated palm oil induced a decrease in 16:0 and an increase in 18:2 while the olive oil diet caused a marked increase in 18:1 and a decrease in most other fatty acids. The differences in the effects of the diets on cellular versus plasma fatty acids suggest that megakaryocytes and platelets have an extensive capacity to regulate their fatty acid composition. Thrombocytosis occurred with the w-3 fatty acid-enriched diet: 12.9± 1.78x 10 s compared with 7.45±1.08xl05platelets per microliter of platelet-rich plasma in control animals. There was an increase in megakaryocyte size, ploidy, and morphological stage (cytoplasmic maturation) with the to-3 fatty acid-enriched diet but not with the other diets. The to-3 fatty acid-enriched diet decreased platelet thromboxane production while the other diets had no effect. Platelet hypersensitivity was suggested in collagen aggregation studies with olive oil but not with the hydrogenated palm oil diet. Although saturated fatty acid diets are thought to be athero|>enic, this diet had no affect on platelet function. The possibility that olive oil-enriched diets can increase platelet sensitivity and thereby augment thrombosis should be considered when making recommendations for increasing the dietary intake of monounsaturated fatty acids.

ISSN:1049-8834    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Noninvasive in situ evaluations of pulsatile changes of blood pressure and arterial diameter were performed at the sites of the common carotid and femoral arteries in a population of 78 untreated normotensive and hypertensive subjects. Arterial segments were studied by using an original echotracking technique for internal diameter and validated applanation tonometry for local pulse pressure measurements. Whereas mean arterial pressure is known to be identical in all parts of the arterial tree, pulse pressure was significantly lower in the carotid (52.7±2.2 mm Hg) than in the brachial (62.0±2.0 mm Hg) or femoral (62.5 ±2.5 mm Hg) arteries. Despite a higher pulse pressure and diastolic diameter, the femoral artery had a lower pulsatile change in diameter (3.47±0.18% versus 6.07+0.28%;p<0.0001) and distensibility coefficient (9.36±0.58 versus 21.60+1.75 xlO"3kPa"1) than the carotid artery. Local cross-sectional compliance of the carotid artery was higher than that of the femoral artery (7.42±0.46 versus 6.20±0.28 m2kPa"110~7;p<0.05). Whereas age was strongly correlated with arterial parameters at the site of the carotid artery (pulse pressure:r=0.54,p<0.0001; pulsatile change in arterial diameter:r=−0.62,p<0.0001; distensibility coefficient:r=−0.70,p<0.0001), no significant correlation was observed at the femoral artery. Mean blood pressure was the second factor of carotid artery alterations: the higher the mean blood pressure, the lower the distensibility of this artery (r= − 0.36,p<0.01). Since no atherosclerotic lesions were detected in the studied subjects, it is suggested that, for the same mean arterial pressure 1) the common carotid artery is exposed to lower pulse pressure than the common femoral artery, 2) the common carotid artery is a highly compliant artery with a strong alteration of its viscoelastic properties with age, and 3) the common femoral artery has smaller mechanical "buffering" properties than the carotid artery, with little influence by aging. This study provides evidence that the effects of aging and elevated blood pressure differ substantially in the different portions of the arterial tree.

ISSN:1049-8834    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Fourteen patients suffering from familial hypercholesterolemia (type Ha) participated in a double-blind, placebo-controlled trial that evaluated! the effects of fish oil ethyl ester (K-85, 5.7 g/day) or a hydroxymethylglutaryl coenzyme A reductase inhibitor (lovastatin, 40 mg/day) alone or in combination on lipid metabolism and bleeding time at rest and after standardized exercise. Lovastatin treatment reduced total cholesterol (−27%), low density lipoprotein cholesterol (−37%), and triglycerides (−18%), whereas high density lipoprotein cholesterol increased significantly (14%). K-85 affected total (−4%), low density lipoprotein (−9%), and high density lipoprotein (+7%) cholesterol insignificantly, whereas the triglyceride level decreased by 24% (p<0.001). The combined regimen caused an additive decrease in the triglyceride level (41%), which differed significantly (p<0.01) from that gained by lovastatin alone. Under basal conditions the bleeding time was no), influenced by the different interventions. Standardized exercise shortened the bleeding time by 19% (P<0.001) and 16% (p<0.001) before intervention and after lovastatin treatment, respectively. After K-85 alone or in combination with lovastatin, the exerciseinduced shortening of the bleeding time was totally inhibited, which may reflect a favorable influence of fish oil on the platelet-vessel wall interaction in these high-risk patients.

ISSN:1049-8834    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Activation of factor IX in an umbilical vein model was established to result solely from factor Vila/tissue factor (TF) activity generated within the umbilical vein wall, and the model was then used to study regulation of such extravascular factor VIIa-TF complexes. Vein segments were filled with a reaction mixture containing factor Vila, Ca2+, a substrate, either [3H] factor IX or [J X, and a test material. Subsamples were assayed for activation peptide release. Test materials included defibrinated plasma or recombinant protein as a source of TF pathway inhibitor (TFPI), recombinant factor Vila to 10 times plasma factor VII concentrations, and annexin V. A plasma concentration of TFPI inhibited but did not totally suppress factor VIIa/TF activity. Reducing the TFPI concentration by 50% markedly reduced the inhibition. A 10-fold increase in the factor Vila concentration in reaction mixtures failed to accelerate factor Xa generation. Annexin V, in contrast to its inhibition of factor VIIa/TF formed with TF reconstituted into mixed phospholipid vesicles, failed to inhibit factor VIIa-TF complexes formed within the vessel wall. We conclude that 1) moderate variation in plasma TFPI concentration or activity may affect TFPI's ability to inhibit factor VIIa/TF activity during hemostasis, 2) a plasma concentration of factor VII suffices to saturate TF sites exposed in a vessel after tissue injury, and 3) the resistance of factor VIIa-TF complexes to inhibition by annexin V suggests that they are formed in the umbilical vein model primarily on cell surfaces.

ISSN:1049-8834    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Arteriosclerotic intimal proliferation is one of the main long-term complications of organ transplantation. Low-molecular-weight, heparin-like molecules prevent myointimal proliferation in arterial wall injury and limit rejection in skin allografts. Cyclosporin limits rejection but has no major effect on intimal proliferation. Therefore, an experimental protocol was designed to test whether heparin-like molecules interacted with low doses of cyclosporin to prevent arterial wall immune system injury and response in a model arterial graft rejection in normotensive and hypertensive rats. Aortic allografts were performed spontaneously hypertensive rats (SHRs) and Wistar-Kyoto (WKY) normotensive control rats. Four groups of 10 allografted (SHR and WKY) rats were used: one group was treated with placebo, one with low doses of cyclosporin (2 nig/kg body wt per day), one with low-molecular-weight, heparin-like molecule (1 nig/kg body wt hour), and one with low doses of cyclosporin plus low-molecular-weight, heparin-like molecule. Ten SHRs and 10 WKYs were isografted and served as the control groups. All rats were killed 8 weeks after aortic grafting. Structural parameters of the grafted segment were measured by morphometric analysis on formalin-fixed sections with specific stains. The classical signs of immune system injury and response were present in the untreated allografts in SHRs and WKYs: inflammatory infiltration of the adventitia, medial injury, intimal proliferative response. Low doses of cyclosporin had a significant beneficial effect on immune medial injury by increasing medial thickness and the number of remaining smooth muscle cells decreasing the extracellular matrix injury. Cyclosporin had no protective effect on intimal proliferation. Low-molecularweight, heparin-like molecules had a beneficial effect on both the medial injury and the intimal proliferative response that was independent of blood pressure. Heparin-like molecules increased medial thickness and partially prevented smooth muscle cell loss and extracellular matrix attack. They also significantly decreased the intimal thickness by acting more on the collagen content than on the smooth muscle cell density. Low doses of cyclosporin plus heparin-like molecules had a marked effect in preventing the arterial wall injury and response. This combination resulted in a normal medial appearance, increased medial thickness and smooth muscle cell number, and no intimal proliferation or adventitial inflammation. Thus, heparin-like molecules appear to act in concert with low doses of cyclosporin preventing rejection-induced arterial wall remodeling in an experimental model of aortic allograft in rats, and their effects are independent blood pressure.

ISSN:1049-8834    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

To isolate the genes involved in the cell cycle G, phase progression of arterial smooth muscle cells (SMCs), a cDNA clone (Mil) was previously selected by differential hybridization screening of a mid-G, serum-stimulated SMC cDNA library. The delay of induction after mitogenic stimulation, time of expression, and need for new protein synthesis for full expression made it possible to classify this gene in the "delayed early" gene group. Determination of the partial Mil cDNA sequence showed full homology with the osteopontin gene (secreted phosphoprotein 1, 2ar), an Arg-Gly-Asp-containing extracellular matrix protein. Osteopontin mRNA was also detected in the aorta at levels as high as in the kidney but lower than in bone, two tissues in which it has been previously detected. In vitro analysis of osteopontin expression in serum-stimulated quiescent SMCs and asynchronously cycling SMCs demonstrated that osteopontin overexpression was associated with SMC proliferation. In view of our results, the high osteopontin expression observed by others in the injured carotid artery could be explained by the involvement of SMCs in the proliferative process. Taken together, these results suggest that osteopontin may play an important role in pathological processes that are associated with arterial SMC proliferation, such as atherosclerosis or restenosis.

ISSN:1049-8834    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Apolipoprotein (apo) A-IV has been proposed to play a role in reverse cholesterol transport. ApoA-IV- containing lipoprotein particles (A-IVLp) were isolated from human plasma and interstitial fluid characterized by immunoaffinity chromatography. Two major A-IVLp subpopulations, lipoprotein particles containing apoA-IV with apoA-I (LpA-I:A-IV) and lipoprotein particles containing apoA-IV without apoA-I (LpA-IV), were identified. The larger subpopulation of A-IVLp is the LpA-IV that represents 70% (protein mass) of the initial particles. Only 5.8% of apoA-I V was recovered in retained fraction after affinity chromatography with an anti-apoA-I immunosorbent. ApoA-I, apoA-II, apoA-IV, apoB, apoC-III, apoD, apoE, apoH, lecithin: cholesterol acyltransferase (LCAT), cholesteryl ester transfer (CET) protein, proline-rich protein, and a protein ofMr59,000 were detected in the A-IVLp. These particles contain more than 20% triglycerides (lipid mass). ApoA-IV-containing particles that were isolated from plasma are heterogeneous in size, consisting of two major populations with Stokes' diameters of 10.3 nm and 9.3 nm. Both subpopulations of A-IVLp contain LCAT and CET activities promote cholesterol efflux from cholesterol-preloaded adipose cells. These data support the hypothesis that A-IVLp particles may be involved in reverse cholesterol transport.

ISSN:1049-8834    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

The concentrations of serum lipoproteins, especially those of low density (LDL) and high density (HDL) lipoprotein, are related to the pathogenesis of arteriosclerosis. However, there is a lack of data concerning lipoprotein distribution in the human arteriosclerotic plaque. To detect these lipoproteins, we performed immunogold labeling on ultrathin sections of fixed and embedded human arteriosclerotic tissue. We used a panel of specific antibodies to different lipoproteins and their apolipoprotein constituents, namely LDL, formaldehyde-fixed LDL, apolipoprotein B-100, HDL, and formaldehyde-fixed apolipoprotein A-I. We also applied antibodies to a-actin and cathepsin D to characterize the cells and organelles involved in lipoprotein uptake and metabolism. Semiquantitative evaluation was carried out for a detailed comparison of the results obtained. Electron microscopic examination revealed that the majority of HDL and LDL in the pathological tissue was localized intracellularly in macrophage-derived foam cells and smooth muscle cells, whereas only LDL was found in the extracellular matrix. In some cases, we observed an intracellular accumulation of lipoproteins in electron-dense vesicles, which appeared to be of lysosomal origin, as shown by double labeling with an antibody to cathepsin D. These vesicles were present only in macrophage-derived foam cells, which were localized in the necrotic cores of arteriosclerotic plaques, and could not be found in healthy tissue or in the early stages of arteriosclerotic disease.

ISSN:1049-8834    

出版商:OVID    

年代:1993

数据来源: OVID

ISSN:1049-8834    

出版商:OVID    

年代:1993

数据来源: OVID