Lipoprotein (a), C-reactive protein and some metabolic cardiovascular risk factors in type 2 DM

<p>Abstract</p> <p>Background</p> <p>Lipoprotein (a) (LP (a) is an independent cardiovascular risk factor that is not widely studied in people of sub-Saharan African origin. The aim of this report is to determine the frequency of occurrence of elevated Lp (a) and possible relationship with total cholesterol (TCHOL), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglycerides (TG), C reactive protein (CRP) and serum uric acid (SUA).</p> <p>Methods</p> <p>This is a cross sectional study carried out in 200 Nigerian patients with type 2 DM and 100 sex and age matched healthy Controls aged between 32-86 years. We determined the frequency of occurrence of elevated Lp (a) levels in the study subjects and compared clinical and biochemical variables between type 2 diabetic patients and non-diabetic patients. Clinical and biochemical parameters were also compared between subjects with type 2 DM who had elevated LP (a) and normal LP (a) levels. Long term glycaemic control using glycosylated haemoglobin was determined and compared in the study subjects. Test statistics used include chi square, correlation coefficient analysis and Student's t test.</p> <p>Results</p> <p>The mean Lp(a) concentration differed significantly between type 2 diabetic patients and the Control subjects (18.7 (5.8) mg/dl vs 23 (6.8) mg/dl, 0.00001). Similarly, the prevalence of high LP (a) levels in type 2 DM patients was significantly higher than that of the Control subjects (12.5% vs 4%, p-0.019). The mean levels of the lipid profile parameters (TCHOL, LDL-C, TG, LDL/HDL) and CRP were significantly higher in DM patients than in the Control subjects. The mean LP (a) levels were comparable in both sexes and in DM subjects with and without hypertension. TG was the only parameter that differed significantly between subjects with elevated Lp (a) levels and those with normal Lp (a) levels. There was a significant positive correlation (r) between Lp(a) levels and TG, LDL-C. TCHOL, LDL/HDL and uric acid. No association was found between Lp(a) and clinical parameters such as age and anthropometric indices.</p> <p>Conclusion</p> <p>We have showed that Lp (a), CRP and other CVS risk factors cluster more in patients with DM than non DM patients. Serum Lp (a) levels are not associated with anthropometric and glycaemic indices.</p

Contribution of Recipient-Derived Cells in Allograft Neointima Formation and the Response to Stent Implantation

Allograft coronary disease is the dominant cause of increased risk of death after cardiac transplantation. While the percutaneous insertion of stents is the most efficacious revascularization strategy for allograft coronary disease there is a high incidence of stent renarrowing. We developed a novel rabbit model of sex-mismatched allograft vascular disease as well as the response to stent implantation. In situ hybridization for the Y-chromosome was employed to detect male cells in the neointima of stented allograft, and the population of recipient derived neointimal cells was measured by quantitative polymerase chain reaction and characterized by immunohistochemistry. To demonstrate the participation of circulatory derived cells in stent neointima formation we infused ex vivo labeled peripheral blood mononuclear cells into native rabbit carotid arteries immediately after stenting. Fourteen days after stenting the neointima area was 58% greater in the stented vs. non-stented allograft segments (p = 0.02). Male cells were detected in the neointima of stented female-to-male allografts. Recipient-derived cells constituted 72.1±5.7% and 81.5±4.2% of neointimal cell population in the non-stented and stented segments, respectively and the corresponding proliferation rates were only 2.7±0.5% and 2.3±0.2%. Some of the recipient-derived neointimal cells were of endothelial lineage. The ex vivo tagged cells constituted 9.0±0.4% of the cells per high power field in the stent neointima 14 days after stenting. These experiments provide important quantitative data regarding the degree to which host-derived blood-borne cells contribute to neointima formation in allograft vasculopathy and the early response to stent implantation

Peroxisome Proliferator-Activated Receptor-Gamma Agonists Suppress Tissue Factor Overexpression in Rat Balloon Injury Model with Paclitaxel Infusion

The role and underlying mechanisms of rosiglitazone, a peroxisome proliferator-activated receptor-gamma (PPAR-γ) agonist, on myocardial infarction are poorly understood. We investigated the effects of this PPAR-γ agonist on the expression of tissue factor (TF), a primary molecule for thrombosis, and elucidated its underlying mechanisms. The PPAR-γ agonist inhibited TF expression in response to TNF-α in human umbilical vein endothelial cells, human monocytic leukemia cell line, and human umbilical arterial smooth muscle cells. The overexpression of TF was mediated by increased phosphorylation of mitogen-activated protein kinase (MAPK), which was blocked by the PPAR-γ agonist. The effective MAPK differed depending on each cell type. Luciferase and ChIP assays showed that transcription factor, activator protein-1 (AP-1), was a pivotal target of the PPAR-γ agonist to lower TF transcription. Intriguingly, two main drugs for drug-eluting stent, paclitaxel or rapamycin, significantly exaggerated thrombin-induced TF expression, which was also effectively blocked by the PPAR-γ agonist in all cell types. This PPAR-γ agonist did not impair TF pathway inhibitor (TFPI) in three cell types. In rat balloon injury model (Sprague-Dawley rats, n = 10/group) with continuous paclitaxel infusion, the PPAR-γ agonist attenuated TF expression by 70±5% (n = 4; P<0.0001) in injured vasculature. Taken together, rosiglitazone reduced TF expression in three critical cell types involved in vascular thrombus formation via MAPK and AP-1 inhibitions. Also, this PPAR-γ agonist reversed the paclitaxel-induced aggravation of TF expression, which suggests a possibility that the benefits might outweigh its risks in a group of patients with paclitaxel-eluting stent implanted