Association of serum MMP-9 with autoantibodies against oxidized LDL.

Monocyte-derived macrophages in atherosclerotic plaques secrete matrix metalloproteinases (MMPs), which may contribute to plaque rupture. There has been much speculation as to which factors precipitate in the arterial inflammation. Oxidized low density lipoprotein (oxLDL) has been suggested to have proinflammatory properties, and it has been shown to increase matrix metalloproteinase-9 (MMP-9) secretion by macrophages in vitro. We determined serum MMP-9 concentration and autoantibodies against oxLDL by ELISA in men with angina pectoris (n=243) and age-matched controls (n=238). The association between serum MMP-9 concentration and autoantibodies against oxLDL was evaluated. Autoantibody level against oxLDL, expressed in optical density units, was significantly higher in subjects with angina pectoris compared to controls (0.100+/-0.064 versus 0.088+/-0.051, respectively, P=0.030), but serum levels of MMP-9 did not differ significantly between these groups (54.2+/-29.9 versus 50.6+/-23.1 microg/l). However, autoantibodies against oxLDL correlated positively with serum MMP-9 (r=0.21, P<0.001). In a multiple regression model (including age, diastolic blood pressure, cholesterol, HDL cholesterol, triglycerides, BMI, smoking and MMP-9) serum MMP-9 (beta=0.200, P<0.001) and smoking (beta=0.179, P<0.001) were significantly associated with autoantibodies against oxLDL. In conclusion, autoantibodies against oxLDL were positively associated with angina pectoris and serum MMP-9. Since autoantibody level against oxLDL could be expected to reflect the degree of oxLDL in the vessel wall, our results suggest that oxLDL is associated with MMP-9 in vivo.

The relation of oxidized LDL autoantibodies and long-term hormone replacement therapy to ultrasonographically assessed atherosclerotic plaque quantity and severity in postmenopausal women.

BACKGROUND: In epidemiologic studies, the incidence of atherosclerosis rises soon after menopause in women, and hormone replacement therapy (HRT) has proved to be useful in preventing onset of clinical manifestations of the disease. However, it is not known how HRT affects sonographically determined atherosclerotic severity (AS) and number of atherosclerotic plaques (NAP) in large arteries. Furthermore, it is not clear how HRT affects oxidation of low density lipoproteins (LDL), which obviously has an important role in the pathogenesis of atherosclerosis. OBJECTIVES: The purpose of the study was to determine whether HRT has a beneficial effect on sonographically determined AS and NAP in large arteries of 101 postmenopausal women compared to 40 controls without HRT. We also studied the interaction of HRT and antibodies against oxidized LDL on AS and NAP progression. RESULTS: Estradiol valerate alone, combined estradiol valerate-levonorgestrel and combined estradiol valerate-medroxyprogesterone acetate therapy are each associated with lower NAP and AS as compared to controls without HRT. In a multiple regression model explaining NAP in the whole study population, the strongest predictors were HRT (P=0.0006) and copper-oxidized LDL cholesterol autoantibodies (P=0.0491). DISCUSSION: Our findings indicate that postmenopausal HRT is associated with a lower total number of atherosclerotic plaques and less severe atherosclerotic lesions, as compared to controls without HRT, and that this outcome may be associated with the effect of HRT on LDL cholesterol oxidation.

Association of carbohydrate-deficient transferrin (CDT) and gamma-glutamyl-transferase (GGT) with serum lipid profile in the Finnish population.

BACKGROUND: Moderate consumption of alcohol may reduce mortality from vascular diseases. The beneficial effects of alcohol may partly be mediated by its effects on lipoprotein metabolism. We studied the connection between alcohol consumption and the serum lipid profile from a well-documented national health program study. METHODS AND RESULTS: Carbohydrate-deficient transferrin (CDT) and gamma-glutamyl-transferase (GGT) were used as biochemical markers for alcohol consumption. The laboratory analyses were carried out on 5675 subjects (3097 males and 2578 females). The subjects were divided into quartiles on the basis of CDT or GGT value. The highest CDT quartile and the lowest GGT quartile seemed to be associated with a favorable lipid profile and the lowest CDT quartile and the highest GGT quartile were associated with an unfavorable lipid profile. Serum high density lipoprotein (HDL) cholesterol values were significantly higher and triglycerides lower with increasing serum CDT concentrations for both men and women. Increasing serum GGT was associated with higher serum total cholesterol and higher triglycerides in both men and women and lower HDL cholesterol in men. CONCLUSIONS: CDT and GGT seem to detect different populations of subjects in regard to lipid metabolism. These observations may lead to a better understanding of the effects of alcohol consumption on lipids as well as mechanisms behind favorable and detrimental effects of alcohol on vascular diseases. CONDENSED ABSTRACT: Carbohydrate-deficient transferrin (CDT) and gamma-glutamyl-transferase (GGT) were used as biochemical markers for alcohol consumption. A total of 3097 males and 2578 females were divided into quartiles on the basis of their CDT or GGT values. The highest CDT quartiles had higher HDL and lower triglycerides, whereas the highest GGT quartiles appeared to be associated with higher total cholesterol and triglycerides in both genders and lower HDL in men. CDT and GGT seem to detect different populations of subjects in regard to lipid metabolism. These observations may have important clinical and public health implications.

Effect of pravastatin in mildly hypercholesterolemic young men on serum matrix metalloproteinases.

Pravastatin decreases serum MMP-9 concentration in clinically healthy men. This may reflect reduction of nonsymptomatic chronic arterial inflammation.

Sequence of a human cDNA encoding Cab45, a Ca2+-binding protein with six EF-hand motifs.

We report the sequence of a human cDNA encoding a deduced 362 amino acid protein with six EF-hand calcium-binding motifs. The protein is a likely human counterpart of the Cab45 protein recently identified in the 3T3-L1 mouse adipocyte cell line [Scherer et al. (1996), J. Cell Biol. 133, 257-268], displaying 87% aa and 83% nt identity with this sequence. The mRNA for human Cab45 is detected ubiquitously in tissue Northern blots.

Electronic consultations and referrals in Kymenlaakso Hospital District.

The meaning of this paper is to introduce the medical network which has been taken to Kymenlaakso Hospital District and the primary experiences in utilizing. Actual numeral results are not ready because of short time. First results will be ready in August 1999.

Apolipoprotein E and A-IV polymorphisms in ethnic Russians living in Estonia.

137 Russians living in Estonia was screened by isoelectric focusing and immunoblotting procedures to determine the distribution of genetic variations in apolipoprotein E (apoE) and apolipoprotein A-IV (apoA-IV) genes. The apoA-IV-2 allele and epsilon4 allele frequency of the Russians tended to be lower than in most other European populations.

Carbohydrate-deficient transferrin and gamma-glutamyltransferase are inversely associated with lipid markers of cardiovascular risk.

BACKGROUND: A variety of epidemiological studies have suggested a U-shaped association between alcohol consumption and atherosclerosis progression and incidence events. Moderate intake of alcohol is considered beneficial, whereas heavy drinking increases cardiovascular disease risk. METHODS: Alcohol and cardiovascular risk-related laboratory tests were carried out in 70 consecutive male employees in connection with an occupational health survey in 1996. Carbohydrate-deficient transferrin (CDT) and gamma-glutamyltransferase (GGT) were used as markers for alcohol consumption. The subjects were divided into quartiles on the basis of CDT or GGT value. RESULTS: The highest CDT quartile had significantly higher serum high-density lipoprotein (HDL)-cholesterol (P < 0.05) than the lowest quartile. The highest GGT quartile had significantly higher serum total cholesterol (P < 0. 01), lower serum HDL-cholesterol (P < 0.05), higher serum low-density lipoprotein (LDL)-cholesterol (P < 0.01) and higher serum triglyceride (P < 0.01) than the lowest quartile. CONCLUSIONS: An explanation for the findings is that high alcohol consumption without significant liver induction increases the level of HDL-cholesterol, whereas high alcohol consumption with induction of liver may have adverse effects on lipoprotein metabolism. The results were interpreted to indicate that CDT and GGT detect different populations of drinkers in regard to cardiovascular lipid risk factors.

Serum matrix metalloproteinase-9 concentration in angiographically assessed coronary artery disease.

Expression of several matrix metalloproteinases (MMPs) in atherosclerotic plaques has been well documented, and there are findings to indicate that arterial inflammation is reflected in increased serum concentration of matrix metalloproteinase-9 (MMP-9). In coronary atherosclerosis, there is enhanced expression of this MMP, which may be predictive of the severity of the disease. We determined the concentrations of serum MMP-9 in 61 patients (47 males, 14 females) who had >50% obstruction in one or more coronary arteries as assessed by coronary angiography before bypass surgery. In a control group of 19 patients (9 males, 10 females) there were no pathological findings in coronary angiography. ANOVA showed that serum MMP-9 concentrations were highest in patients with 3-vessel coronary artery disease (CAD) (57.3+/-39.1 microg/L, p=0.011). The difference remained statistically significant after adjustment for age, diabetes and sex (p=0.025, ANCOVA). When the groups were compared with each other, serum MMP-9 concentration was higher in the patients with 3-vessel CAD than in those with 1- or 2-vessel CAD (40.4+/-25.1 microg/L, p=0.044) or in the controls (32.2+/- 16.1 microg/L, p=0.007). These results show that serum MMP-9 is elevated in patients with severe coronary stenosis compared with controls. Since MMP-9 has been suggested to reflect inflammation in atherosclerotic plaques, it may be useful in the evaluation of the severity of cardiovascular disease.

Serum homocysteine does not associate with uncomplicated coronary heart disease.

BACKGROUND: Elevated serum homocysteine concentrations have been related to coronary heart disease. However, the association has not indisputably been proven, and the mechanisms by which homocysteine may be atherogenic have only partially been elucidated. The objective of the present study was to investigate whether serum homocysteine is associated with angina pectoris and myocardial infarction. METHODS: We compared serum homocysteine concentrations in subjects with clinical evidence of angina pectoris or history of myocardial infarction to age-matched controls. The study included 248 males, who participated in a large cross-sectional risk factor survey carried out in five geographic areas in Finland. RESULTS: Serum homocysteine concentration was significantly higher in subjects with a history of myocardial infarction compared to controls (15.3 micromol L-1 and 13.9 micromol L-1 respectively, P = 0.037). In a logistic regression model including several cardiovascular risk factors, serum homocysteine was significantly associated with myocardial infarction (95% CI 1.0157-1.2990, P = 0.027). Serum homocysteine concentrations did not differ between subjects with angina pectoris and age-matched controls (13.9 micromol L-1 and 14.2 micromol L-1 respectively). CONCLUSIONS: Our results suggest that elevated serum homocysteine is associated with myocardial infarction but not with uncomplicated coronary heart disease.

Association of serum sialic acid and MMP-9 with lipids and inflammatory markers.

BACKGROUND: Inflammation of the arterial wall has emerged to be an important contributor to the process of atherosclerosis, the major cause of coronary heart disease. Several factors are currently under investigation as inflammatory markers of atherosclerosis. Serum sialic acid and matrix metalloproteinase-9 may provide such markers. We studied their association with the lipid profile and with the inflammatory markers C-reactive protein and leukocyte count in a clinically healthy population of men. MATERIALS AND METHODS: Cardiovascular risk-related laboratory tests were carried out in 65 consecutive male employees in connection with an occupational health survey in 1996. The subjects were divided into tertiles on the basis of serum sialic acid or matrix metalloproteinase-9 concentration. RESULTS: In a stepwise polychotomous logistic regression model adjusting for coronary heart disease risk factors, serum sialic acid concentration was not associated with markers of inflammation but rather with the lipid risk factors of atherosclerosis: inversely with HDL cholesterol (OR = 0.081, 95% CI 0.0068-0.97) and positively with total cholesterol (OR = 2.4, 95% CI 1-5.6). Matrix metalloproteinase-9 levels had a significant positive correlation with the leukocyte count (OR = 2.3, 95% CI 1.4-4). CONCLUSIONS: Serum sialic acid does not appear to be an indicator of inflammation but is somehow connected with the level of total and HDL cholesterol. Serum matrix metalloproteinase-9 may provide a useful marker of inflammation because it correlates with the leukocyte count and is not associated with the lipid profile.

Trends in serum cholesterol and lifestyle indicators in Members of the Finnish Parliament.

OBJECTIVE: To examine the extent that public health promotion activity is reflected in life styles of national decision makers, by analysing trends in coronary heart disease risk factors in Members of the Finnish Parliament (MPs). METHODS: The MPs were studied at the beginning of two subsequent 4-year parliamentary periods between 1991 and 1999. The studies included analyses of serum total cholesterol and high-density lipoprotein (HDL) cholesterol, and a questionnaire about alcohol, smoking and physical activity. RESULTS: Serum total cholesterol was above the national recommendation of 5.0 mmol/l in 85% of the male MPs and 62% of the female MPs. The mean level of serum total cholesterol increased in female MPs during the 4-year follow-up period (P < 0.05), and male MPs showed an increase in mean HDL cholesterol (P < 0.001). The mean body mass index increased in both male (P < 0.01) and female (P < 0.01) MPs during the same period. Alcohol consumption, smoking and physical activity were unchanged during follow-up. CONCLUSIONS: From the public health perspective, serum cholesterol is too high in most MPs, and the level in males is above the national average. Both males and females put on weight during the parliamentary period, and male MPs also showed an increase in HDL cholesterol, which may be explained by other lifestyle factors.