plasminogen activator inhibitor-1 [PAI-1] gene locus 4g/5g polymorphism and PAI-1 plasma levels in Egyptian patients with myocardial infarction

Activation of inflammation and coagulation are closely related and mutually interdependent in myocardial infarction [MI]. The acute-phase protein, plasminogen activator inhibitor-1 [PAI-1], is a key element in the inhibition of fibrinolysis. Elevated levels of PAI-1 have been related to MI. There are controversial data regarding the impact of 4G/5G polymorphism of the PAI-1 gene in the pathogenesis of MI. Patients with MI exhibited significantly higher plasma PAI-1 levels than controls. Significant changes in PAI-1 levels were found in homozygous PAI-1 4G/4G carriers compared with other 4G/5G genotype carriers in patients with MI. The allelic frequency of 4G among the patients was 83.3%; that of 5G was 16.7%. In the control group, the allelic frequencies of 4G and 5G were 62.0% and 38.0% respectively. The difference in genotype distribution between the two groups was significant. There were significant associations between MI and the 4G allele, hypertension, smoking, and family history of coronary heart disease. Our findings suggest that the 4G allele of the PAI-1 promoter polymorphism is an independent risk factor for MI. The emerging evidence that circulating levels of PAI-1 relate to genotype at a common polymorphism in the promoter of the PAI-1 gene has opened the possibility of using PAI-1 genotype as a surrogate measure of pre-morbid PAI-1 levels to tease apart the cause and effect limbs of the PAI-1-coronary disease relationship. The detection of this allele along with other risk factors may therefore be useful in primary prevention

Biochemical study on some adipocyto-kines in chronic renal failure: their relationship to endothelial dysfunction and inflammation

Chronic renal failure has been associated with impaired immunity and subclinical inflammation involving cytokines derived from adipose tissue - adipocytokines. Deteriorating renal function may increase overall inflammatory responses because of the decreased renal clearance of factors that are directly or indirectly involved in inflammation. Declining renal function may also affect the levels of additional inflammatory molecules such as C-reactive protein [CRP] and interleukin-6.The aim of the study was to assess visfatin and apelin in correlation with markers of endothelial cell injury and inflammation in 20 patients with CRF and 20 age- and sex-matched healthy controls.We assessed visfatin and apelin, markers of: coagulation: TAT [thrombin-antithrombin complexes]; fibrinolysis: tPA [tissue plasminogen activator] and PAI-1 [plasminogen activator inhibitor-1]; endothelial function/injury: 1CAM [intracellular adhesion molecule], VCAM [vascular cell adhesion molecule], CD40L and E-selectin and inflammation: hsCRP andIL-lbeta. Visfatin, apelin, TAT, ICAM, VCAM, CD40L, PAI-1, E-selectin, hsCRP, IL-lbeta and triglycerides were elevated while serum albumin and t-PA were decreased in CRF patients when compared with the control group.Significant positive correlations were found between visfatin on one hand and each of apelin, t-PA, PAI-1, E-selectin, ICAM, VCAM, hsCRP, LL-lbeta, CD40L and triglycerides on the other hand in patients with CRF.Also, Significant positive correlations were found between Apelin and each of EL-lbeta, E-selectin, ICAM, VCAM, creatinine and triglycerides in CRF