The impact of TFPI on coronary atherosclerotic burden.

OBJECTIVES: We aimed to associate a coronary artery disease (CAD) presence and severity with endothelial dysfunction (ED), carotid intima media thickness (CIMT) and Tissue Factor Pathway Inhibitor (TFPI). BACKGROUND: ED has a central role in atherosclerosis. CIMT and TFPI activity are also related with atherosclerosis and CAD. METHODS: In our prospective observational study, 50 patients had CAD and 30 had normal coronary arteries. Endothelial function was evaluated by endothelium-dependent flow-mediated dilatation (FMD) and nitroglycerine-mediated dilatation (NMD) measurements. CIMT and Serum TFPI levels were also measured. RESULTS: TFPI was a statistically significant determinant between the two groups with an increased level in CAD (+) group (84.9 ± 19.3 vs 70.2 ± 14.7, p = 0.001). There was a positive correlation between CIMT and Gensini (r = 0.34, p = 0.014). There was a strong negative correlation between Gensini and FMD-NMD, statistically significant (FMD: r = -0.715, p < 0.001; NMD: r = -0.718, p < 0.001). CONCLUSION: We observed that ED, increased CIMT and TFPI levels were associated with CAD. Additionally, increased CIMT measurements and decreased FMD and NMD values had a positive correlation with GSS (Tab. 4, Fig. 6, Ref. 50).

11ß-hydroxysteroid dehydrogenase type 1 gene expression is increased in ascending aorta tissue of metabolic syndrome patients with coronary artery disease.

11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD-1) activity and mRNA levels are increased in visceral and subcutaneous adipose tissues of metabolic syndrome subjects. We analyzed 11ß-HSD-1 expression in human epicardial adipose (EA) and ascending aorta (AA) tissues of metabolic syndrome patients and examined their contribution to the development of coronary atherosclerosis. The 11ß-HSD-1 expression was evaluated by qRT-PCR in EA and AA tissues of 20 metabolic syndrome patients with coronary artery disease (metabolic syndrome group) and 10 non-metabolic syndrome patients without coronary artery disease (controls). 11ß-HSD-1 expression was increased in EA and AA tissues of the metabolic syndrome group (4.1- and 5.5-fold, respectively). A significant positive correlation was found between 11ß-HSD-1 expression in EA tissue and waist hip ratio and 11ß-HSD-1 expression in AA tissue and body mass index, while a negative correlation was found between 11ß-HSD-1 expression in EA tissue and HDL. Expression of CD68, a macrophage marker, was significantly increased in both tissues of the metabolic syndrome group; it was 2-fold higher in AA tissue compared to EA tissue in the metabolic syndrome group. Our findings of increased expression of 11ß-HSD-1 and CD68 in AA tissue of the metabolic syndrome group lead us to suggest that they contribute to coronary atherosclerosis in metabolic syndrome. This positive correlation between obesity markers and 11ß-HSD-1 in AA and EA tissues strengthens the evidence that 11ß-HSD-1 has a role in metabolic syndrome. To the best of our knowledge, this is the first report showing 11ß-HSD-1 and CD68 expression in AA tissue of metabolic syndrome patients. We suggest that there is tissue-specific expression of 11ß-HSD-1 in metabolic syndrome and associated cardiovascular disorders.

The interrelationship between insulin secretion and action in type 2 diabetes mellitus with different degrees of obesity: evidence supporting central obesity.

This paper investigates the relative role of the impairment of insulin secretion and action in the pathogenesis of Type 2 diabetes mellitus (T2DM). The parameters indicating insulin secretion and action were calculated from the data obtained during oral glucose tolerance test (OGTT), in 156 age- and sex-matched T2DM patients divided in 4 groups according to their body mass index (BMI, I = 20.0-24.9, II = 25.0-29.9, III = 30.0-39.9 and IV > 40.0 kg/m2). After obtaining baseline biomedical parameters (plasma glucose, serum insulin, cholesterol, HDL-cholesterol, triglycerides, BMI, and amount of fat tissue), the rates of insulin secretory capacity and insulin action were obtained from OGTT and compared between the T2DM patients with normal body weight and different grades of obesity. Beta-cell secretory capacity of the participants was found to be proportionally and significantly higher in graded obese than that of the normal body weight patients. The rates of hepatic as well as peripheral insulin resistance in obese groups proportionally and significantly rise in comparison with that of non-obese diabetics. In addition, these parameters are shown to be related to the body fat, presumably visceral in origin. In conclusion, hyperglycemia-hyperinsulinemia observed in obese and T2DM patients might be due, in part, to increased capacity of insulin secretion, and to exaggerated hepatic glucose production because of hepatic insulin resistance, respectively.