ISSN:1049-8834    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

The effect of 5 days of oral nifedipine treatment (~t mg/kg per day in drinking water) on low density lipoprotein (LDL) and cholesterol accumulation in rabbit arteries was determined. Compared with control aortas, nifedipine treatment (w=5) significantly reduced homologous125I-tyramine cellobiose- LDL accumulation (control versus nifedipine: 45.93±4.3 versus 20.14±3.1 ng LDL per milligram dry weight xlO-3,p=0.001) while the reduction of human LDL accumulation (n=5) was not significant (49.1 ±6.1 versus 35.5±4.1 ng LDL per milligram dry weight xlO~3). Aortic accumulation of orally administered ['H] cholesterol was also inhibited by nifedipine (352 ±34 versus 257 ±16 ng cholesterol per milligram dry weight xlO-3,n=10,p=0.022). These findings suggest a possible mechanism for the antiatherosclerotic effect of nifedipine.

ISSN:1049-8834    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

A nonhypotensive dose of atrial natriuretic peptide (ANP) was infused (60 pg/kg body wt per day s.c. by osmotic pump) for 25 days in 16-week-old normotensive Wistar-Kyoto rats (WKYs, TI = 12) and age-matched spontaneously hypertensive rats (SHRs, n = 12). During the infusion period, systolic blood pressure, urinary volume, and cyclic guanosine monophosphate (cGMP) excretion/12 hr were measured once a week in both groups. Then mechanical and morphological properties of the arterial wall and plasma ANP levels were assessed and compared with those from control groups of SHRs («=8) and WKYs (n=8) receiving a saline vehicle. The compliance (CC) of the in situ localized carotid artery was measured for pressures ranging from 25 to 175 mm Hg under control conditions and after "poisoning" of smooth muscle tone by potassium cyanide. After pressure fixation, the medial thickness, elastin and collagen contents, and the size and number of nuclei were measured in the thoracic descending aorta. In WKYs, ANP did not modify either mechanical or structural properties of the arterial wall or biochemical parameters. Conversely, in ANP-treated SHRs, CC was significantly increased compared with untreated SHRs under basal conditions (p<0.03) and after potassium cyanide poisoning (p<0.02). Structural properties were also modified by ANP in SHRs, i.e., medial thickness (129.3±4.1 versus 113.1 ±3.3 jum,p<0.01) and nuclear size (8.81 ±0.28 versus 5.52±0.20 /μm2;p<0.0001) in untreated and treated SHRs, respectively. Furthermore, urinary volume and cGMP content were significantly increased during ANP infusion in treated SHRs (p<0.05). The present results indicate concomitant modifications of mechanical and structural properties of the arterial wall in SHRs chronically treated with low doses of ANP. These long-term effects of ANP could be involved in the remodeling of the arterial wall observed during hypertension and could have beneficial effects on cardiovascular diseases in chronic sustained hypertension.

ISSN:1049-8834    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Fifty-one pigs were fed a low-cholesterol basal diet, to which either 10% (by weight) of lard fat (group INORM,n=l), 2% cholesterol plus 8% lard fat (group II,n=33), or 2% cholesterol plus 4% lard fat plus 4% fish oil (group IIIPREVIn=H) was added. In all pigs, the left anterior descending coronary artery and the abdominal aorta were denuded at 1 month. In the first 24 hours thereafter, three animals in group II and two in group IIIPREv died suddenly. After 3 months, 0.5% bile acids was added to the diet in groups II and IIIPREV After 8 months the degree of atherosclerosis was evaluated in groups INORM and IIIPREV and in 14 animals from group II (HIND)- At 4 months, one animal from Group II died of pneumonia. For the next 4 months (postinduction period), the remaining 15 animals from group II received the basal diet, to which either 10% lard fat (group 11,$,n=6) or 5% lard fat plus 5% fish oil (group IIro,n=9) was added. The hypercholesterolemic diet increased plasma cholesterol from 2 to 9-12 mM after 8 months. Fish oil had no major effects on plasma lipids during both induction and postinduction. Superoxide production by granulocytes in response to the membrane receptor-dependent A'-forniyl-methionyl-leucyl-phenylalanine (fMLP) gave a higher response in group IIINDthan in group INORM-In group IIIPREV > the response to phorbol myristate acetate (PMA) and fMLP was lowered, while in groups IITOand 11,$ the responses to PMA and fMLP were not affected. The response to serum-treated zymosan was similar in all groups. Abrasion caused increases in free cholesterol (40%) and phospholipids (46%) in the abdominal aortas of group INORM animals. Hypercholesterolemia increased both free and esterified cholesterol in the entire aorta. Fish oil prevented accumulation of free cholesterol in the nonabraded ascending aorta during induction and further accumulation of free cholesterol and phospholipids in the abdominal aorta during postinduction. In the nonabraded ascending aorta, triglycerides were significantly (almost five times) lower in group IIF0than in group II,j. During both induction and postinduction, a large incorporation of n-3 polyunsaturated fatty acids (up to 20%) occurred in plasma and aortic cholesterol esters and phospholipids of groups IIroand IIIPREV In plasma lipids the major fatty acid was always 20: Sn-3, but in aortic lipids the incorporation of its elongated product 22: 5n-3 was generally equal to 20: 5n-3. Sudanophilia of the aorta was 0% for group INORM > 33% for group II)ND, 35% for group HIPREV, 9% for group IIu, and 7% for group IIFO. Luminal encroachment of the coronary arteries in groups INORM and IIINDwas similar. Fish oil (group IIIPREV) had no effect on the development of coronary atherosclerosis. Despite the normocholesterolemia during the postinduction period in group IILF, coronary atherosclerosis progressed to 12% in the right coronary artery and to 18% in the left anterior descending coronary artery, while in group IIF0these values were 5% and 10%, respectively. In conclusion, isocaloric administration of n-3 fatty acid ethyl esters did not prevent the development of coronary atherosclerosis (luminal encroachment) or aortic atherosclerosis (sudanophilia and aortic lipid content). However, fish oil feeding during the postinduction period attenuated the progression of coronary atherosclerosis and the accumulation of lipids in the damaged aortic wall, while aortic atherosclerosis as measured by sudanophilia was not affected. This study shows that the criteria used to assess experimental atherosclerosis are essential in the evaluation of the effects of n-3 fatty acids.

ISSN:1049-8834    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

To evaluate the prevalence and risk factors of asymptomatic carotid artery disease, we analyzed a sample of 909 men and women (aged 40-79 years) drawn from the community-based Bruneck Ischemic Heart Disease and Stroke Prevention Study. For the four decades of age (40–49, 50-59, 60-69, and 70-79 years), respective prevalence rates as assessed by duplex scanning were found to be 8.2%, 39.7%, 66.4%, and 82.5% in men and 3.3%, 22.3%, 48.7%, and 76.7% in women. High-grade stenosis (>80%) classified by Doppler criteria was twice as frequent in men (2.4%) as in women (1.1%). Age and sex were found to be particularly strong and independent predictors of asymptomatic carotid artery disease. Accordingly, separate logistic regression models were developed for both men and women in the elderly (65–79 years) and middle-aged (50–64 years) groups. Systolic blood pressure turned out to be the only attribute with independent significance in all subgroups examined. Cigarette smoking, recorded as pack-years, emerged as the leading risk factor of carotid atherosclerosis in men. Serum fibrinogen levels were found to be highly indicative of carotid artery disease in elderly men and women. For apolipoprotein B predictive significance was observed in the middle-aged populations, whereas apolipoprotein A-I had a protective effect in elderly women. Diabetes mellitus completed the risk factor profile for elderly men. In summary, the relation between cardiovascular risk factors and asymptomatic carotid artery disease showed a dynamic dependence on sex and age. These findings may help to improve the efficacy of risk prediction in the general population and facilitate well-directed preventive measures.

ISSN:1049-8834    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Plasminogen activator inhibitor-1 (PAI-1) is present in the platelet $-granule and is released on platelet activation. Platelet PAI-1 could either be synthesized by the megakaryocyte or taken up from the plasma. In this report we confirm the presence of PAI-1 protein in human megakaryocytes by Western blot analysis and show its synthesis in guinea pig megakaryocytes by metabolic labeling. We document the presence of PAI-1 mRNA in human platelets and show a 3-kb mRNA species on Northern blot analysis of guinea pig megakaryocytes. Neither untreated CHRF-288 cells, a megakaryoyblastic cell line, nor human erythroleukemia (HEL) cells expressed PAI-1 mRNA. Phorbol ester (phorbol 12-myristate 13-acetate, 160 nM) treatment of CHRF-288 and HEL cells for 4 days induced PAI-1 mRNA expression in CHRF-288 cells but not in HEL cells. These studies show that PAI-1 is synthesized by megakaryocytes. Megakaryocytes most likely determine the PAI-1 content of platelets and thereby establish the antifibrinolytic potential of the platelet.

ISSN:1049-8834    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Lipoprotein(a) (Lp[a]) is generally considered to be a risk factor for the development of cardiovascular disease, but little is known about the possible influence of obesity on the circulating levels of this lipoprotein. The present study was undertaken to examine this aspect in 136 menstrually active women by comparing the serum concentrations of Lp(a) between 72 obese and 64 age-matched nonobese women. Since an adverse effect of androgens and a protective effect of estrogens have been described for plasma lipoprotein profiles in obese women, the relation between the circulating levels of Lp(a) and those of these other hormones was also investigated in obese patients. In addition, other lipoproteins, anthropometric parameters (body mass index and waist-to-hip ratio), and insulin were evaluated. The levels of Lp(a) were not significantly different (Mann-Whitney U test × / 3-59;p=0.0582 [NS]) between obese (rank sum, 5,367) and control (rank sum, 3,949) women; in addition, the percentage of patients with high Lp(a) levels (cutoff defined at 30 mg/dL) did not differ between the two groups (obese women, 30%; control, 21.8%; ×2, 0.90; two-sidedp=0.341 [NS]). Moreover, no correlation was found between Lp(a) and body mass index. Lastly, when the Lp(a) prevalence odds ratio for obesity was examined by adjusting the levels of this lipoprotein for age, triglycerides, total cholesterol, and high density lipoprotein cholesterol, the probability value (0.88) was far from significant. In obese women, no correlation was found between the logarithmically transformed Lp(a) concentrations and all the other variables evaluated in the study. In conclusion, the present study shows that the circulating levels of Lp(a) are not influenced by body weight and cardiovascular risk factors commonly associated with obesity, such as enhanced androgenic activity, hyperinsulinemia, adverse lipoprotein profile, and abdominal fat accumulation.

ISSN:1049-8834    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

To determine the effects of an intact extracellular matrix on collagen synthesis, arterial smooth muscle cells (SMCs) were plated sparsely on a cell-free, SMC-derived matrix and examined the following day. Collagen synthesis during a 5-hour incubation by cells on the matrix was reduced to 67% of the control values obtained from cultures on plastic. Total protein synthesis was unaffected. Treatment of the matrix with heparitinase to remove basic fibroblast growth factor (bFGF) before seeding the SMCs abolished the inhibitory effect of the matrix on collagen synthesis. The inhibitory effect was also eliminated by treating the matrix with a neutralizing polyclonal antibody directed against bFGF. Collagen synthesis by SMC cultures grown in wells coated with purified bFGF was only 61% that of control cultures, whereas total protein synthesis remained unchanged. Slot-blot analysis revealed that the relative message level for orl(III) procollagen was reduced in cultures grown on the preexisting matrix or on plastic precoated with bFGF, whereas the al(I) procollagen message was unaffected. These results demonstrate the ability of the extracellular matrix to modulate the synthesis of collagen by arterial SMCs and indicate that bFGF in the matrix is responsible for these effects.

ISSN:1049-8834    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Low density lipoprotein (LDL) subclass phenotype B, characterized by a predominance of small LDL as determined by gradient gel electrophoresis, has been associated with increased risk of coronary heart disease and an atherogenic lipoprotein profile. Previous studies employing complex segregation analysis have demonstrated a major, single gene effect on the inheritance of this phenotype in families. Recently, linkage between this phenotype and variation at the LDL receptor locus on chromosome 19 has been reported. However, variation in LDL subclass phenotypes has also been associated with age, gender, diabetes status, 0-blocker medication, and diet. The present study further evaluates the relative importance of genetic and nongenetic influences on LDL subclass phenotypes and on LDL peak particle diameter (as a reflection of the size of the major LDL subclass) in monozygotic and dizygotic women twin pairs. The analysis is based on 203 monozygotic and 145 dizygotic pairs of adult female twins who participated in the second examination of the Kaiser Permanente Women Twins Study. The average age was 51 years at this exam and 90% were white. Concordance analysis revealed that monozygotic cotwins shared LDL subclass phenotypes more frequently than dizygotic cotwins, and this was confirmed using logistic regression analysis after controlling for potential confounding factors. Heritability analyses suggested that approximately one third to one half of the variation in LDL peak particle diameter, a continuous variable reflecting LDL size, could be attributed to genetic influences. Commingling analysis of the frequency distribution of LDL peak particle diameter identified three distinct subgroups of subjects, one of which corresponded to those subjects with LDL subclass phenotype B. This result could reflect the presence of a major gene effect on LDL size. These analyses in women twins demonstrate substantial genetic influences on LDL size heterogeneity, confirming previous studies in families. In addition, significant nongenetic factors are also apparently operating and thus could provide opportunities for targeted intervention to reduce coronary heart disease risk.

ISSN:1049-8834    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Platelet activation by the stable endoperoxide analogue U46619 is mediated largely by ADP released from platelet-dense granules. Polymorphonuclear leukocytes (PMNs) endowed with ecto-ADPase activity may operate as antiaggregatory cells in platelet aggregation induced by U46619. Unstimulated PMNs were effective in reducing aggregation when platelets were stimulated by threshold concentrations of U46619, whereas at higher concentrations of the stimulus, PMN activation is required. Evidence that the inhibition was mediated by PMN ecto-ADPase activity was obtained by high-performance liquid chromatography analysis, indicating that PMNs were able to efficiently metabolize platelet-active ADP into AMP. Moreover, PMN-derived supernatants were able to inhibit platelet aggregation, suggesting that under this circumstance the inhibition was exerted by an uncharacterized, releasable ADPase activity. This study supports the hypothesis that, besides nitric oxide and hydrogen peroxide, ADPase activity may represent another PMN-mediated pathway capable of regulating platelet activity in areas of reduced blood flow, such as those found in conditions of myocardial ischemia.

ISSN:1049-8834    

出版商:OVID    

年代:1993

数据来源: OVID