Lipoprotein (a) up-regulates the expression of the plasminogen activator inhibitor 2 in human blood monocytes.

Elevated plasma lipoprotein (a) (Lp[a]) and cardiac events show a modest but significant association in various clinical studies. However, the influence of high Lp(a) on the gene expression in blood monocytes as a major cell involved in atherogenesis is poorly described. To identify genes influenced by elevated serum Lp(a), the gene expression was analyzed on a complementary DNA microarray comparing monocytes from a patient with isolated Lp(a) hyperlipidemia and coronary heart disease with monocytes from a healthy blood donor with low Lp(a). By using this approach, numerous genes were found differentially expressed in patient-versus-control monocytes. Verification of these candidates by Northern blot analysis or semiquantitative polymerase chain reaction in monocytes from additional patients with Lp(a) hyperlipidemia and healthy blood donors with elevated Lp(a) confirmed a significant induction of plasminogen activator inhibitor type 2 (PAI-2) messenger RNA (mRNA) in monocytes from male, but not from female, individuals with high Lp(a), indicating that this observation is gender specific. This led also to increased intracellular and secreted PAI-2 protein in monocytes from male probands with Lp(a) hyperlipidemia. Plasminogen activator inhibitor type 1 (PAI-1) mRNA was found suppressed only in the patients' monocytes and not in healthy probands with high Lp(a) levels. Purified Lp(a) induced PAI-2 mRNA and protein and reduced PAI-1 expression in monocytes isolated from various controls. The finding that PAI-2 is elevated in monocytes from male patients with isolated Lp(a) hyperlipidemia and male healthy probands with high Lp(a) and that purified Lp(a) up-regulates PAI-2 in control monocytes in vitro indicate a direct, but gender-specific, effect of Lp(a) for the induction of PAI-2 expression.

Evaluation of serum levels of solubilized adhesion molecules and cytokine receptors in coronary heart disease.

OBJECTIVES: The diagnostic importance of circulating solubilized tumor necrosis factor-alpha receptor II (sTNF-alphaRII) and interleukin-2 receptor in coronary heart disease (CHD) was evaluated. In addition, these variables were correlated with solubilized adhesion molecule levels (i.e., intracellular adhesion molecule [ICAM], vascular cell adhesion molecule [VCAM], and E-selectin). BACKGROUND: Atherosclerosis is considered to be a chronic inflammatory process. Because the immunologic network presents an abundance of positive and negative feedback mechanisms, information obtained from different immunologic variables might be highly redundant. METHODS: In a cross-sectional study design, 60 patients with angiographically proven CHD were compared with 60 individuals who had undergone coronary angiography but in whom no evidence of stenosis could be found (control subjects). Angiography was performed at least one year before the study. Cytokine levels were determined by enzyme-linked immunosorbent assay technique and evaluated by univariate and multivariate statistical methods. RESULTS: All immunologic variables except E-selectin (p = 0.08) significantly discriminated between patients and control subjects. Coronary artery bypass graft surgery after angiography did not lead to significant differences in the variables investigated in the patients with bypass surgery as compared with the subjects without bypass surgery. Receiver-operating characteristics analysis showed comparable test accuracy for solubilized adhesion molecules and cytokine receptors. Multivariate logistic regression analysis, including age, revealed that only ICAM and sTNF-alphaRII were independently correlated with the presence of CHD. Patients belonging to the third tertile of at least one of these two variables demonstrated a 1.6- to 2-fold increased relative risk for the presence of CHD. CONCLUSIONS: We concluded that both circulating ICAM and TNF-alphaRII should be further evaluated as markers for atherosclerotic changes in the coronary system.

Prevalence of risk factors of coronary heart disease in Turks living in Germany: The Giessen Study.

Turkish people represent the majority of immigrants in Germany. Even though a high proportion of Turks has been living in Germany since about 20 years, little is known about risk factors of coronary heart disease (CHD) in this population. In this study a sample of 325 male and 155 female Turks are investigated, who voluntarily underwent a health check-up in Germany. Data about the presence of CHD, risk factors and blood parameters were collected. Mean residence time was 21 and 17 years (males/females). A low percentage of female participants was observed compared to the general Turkish population in Germany. Age adjusted prevalence of CHD reached 9.5% in males and 6.7% in females, respectively. Dyslipoproteinemia (DLP) showed the highest prevalence of all risk factors investigated in both genders. Total cholesterol (TC) levels were comparable to those of other western countries and remarkably higher than reported for the population in Turkey. Besides this, low high density lipoprotein-cholesterol (HDL-C) and apolipoprotein A-I (ApoA-I) levels could be found in the majority of the sample. The highest odds ratios for CHD were estimated for stress and hypertension in males and obesity in females. It is concluded that Turkish immigrants in Germany showed an assimilation of lipid pattern to western populations. However, reasons for low HDL-C levels remain unclear. Changes in the lipid metabolism chiefly seem to contribute to the risk factor pattern of Turkish immigrants in Germany.

Polymorphisms of apolipoproteins A-IV and E in a Turkish population living in Germany.

Human apolipoproteins (apo) E and apo A-IV are polymorphic with significantly different allele frequencies among different ethnic groups. Whereas the variation at the apo E gene locus affects plasma cholesterol levels in all populations studied so far and is associated with longevity in Caucasians, the influence of the common apo A-IV polymorphism on plasma lipoproteins has not been unanimously accepted. We have therefore determined the common apo E and apo A-IV polymorphisms by isoelectric focusing, calculated the respective allele frequencies and studied their effects on plasma lipoproteins in a random sample of 240 nonrelated Turkish subjects (141 males, 99 females) living in Germany and originating from central and eastern Anatolia. When compared with the German population and other Caucasians in Europe a prominence of the apo epsilon 3 allele frequency (0.885) was accompanied by a decrease in the frequencies of both the apo epsilon 2 allele (0.048) and the apo epsilon 4 allele (0.067). Thus, the Turkish population studied here clustered with populations mainly from southern Europe and Japan, which have low epsilon 2 and epsilon 4 allele frequencies. Also, the frequency of the A-IV-1 allele was higher (0.967) and that of the A-IV-2 allele lower (0.033) in the Turkish subjects studied than in other populations. At an average level of total cholesterol of 194.5 +/- 45 mg/dl, no significant influence of the A-IV alleles on plasma lipoproteins was seen. However, apo E and apo B differed significantly between apo E phenotypes, with high levels of apo E and low levels of cholesterol and apo B in carriers of the epsilon 2 allele, and vice versa for the epsilon 4 allele. The average cholesterol excess for the epsilon 2 allele was -7.95 mg/dl, for the epsilon 3 allele, -1.34, and for the epsilon 4 allele, + 14.15 mg/dl. Thus, despite the unusual frequency distribution of the apo E alleles, their effects on plasma lipoproteins are within the range reported for other populations in Europe.