Postangioplasty restenosis: platelet activation and the coagulation-fibrinolysis system as possible factors in the pathogenesis of restenosis.

We investigated the relationship between changes in hemostatic factors and postangioplasty restenosis by evaluating plasma levels of P-selectin, beta-thromboglobulin (BTG), and other markers of the coagulation-fibrinolysis system. Seventy-three consecutive patients (56 men and 17 women) undergoing elective percutaneous transluminal coronary angioplasty (PTCA) were enrolled in this study. Patients with acute myocardial infarction within the previous month, unstable angina pectoris, chronic total occlusion, target lesions involving saphenous vein grafts, or coronary artery bypass grafting within the previous 6 months were excluded. Fasting blood samples were obtained before elective PTCA and at follow-up coronary angiography. In patients with restenosis, plasminogen activator inhibitor type-1 (PAI-1) levels were significantly higher (88.2 +/- 36.1 vs 118.5 +/- 50.0 ng/dl; p< 0.05) and plasmin-plasmin inhibitor complex (PIC) levels were significantly lower (0.76 +/- 0.26 vs 0.61 +/- 0.26 microg/ml; p < 0.02) than at baseline. P-Selectin levels were also significantly higher (192 +/- 68 vs 239 +/- 99 ng/ dl; p<0.01) and a positive correlation existed between P-selectin and BTG levels (r= 0.43; p< 0.05). The higher PAI-1 and lower PIC levels in patients with postangioplasty restenosis suggest that impaired fibrinolysis may play a role in the pathogenesis of restenosis, whereas the positive correlation between P-selectin and BTG levels implies a role for activated platelets in restenosis.

The p53-deficient hemopoietic stem cells: their resistance to radiation-apoptosis, but lasted transiently.

Hemopoietic stem cells lacking with p53 are known to be resistant to radiation apoptosis: p53-product induces, on one hand, the cells that have been injured by radiation to stop cell-cycle at G, phase, and on the other hand the cells that have not been repaired to go into apoptosis. Thus, in the p53-deficient mice, the hemopoietic stem cells after graded dose of radiation show a flatter survival curve for radiation, i.e., like a curve for radio-resistant phenotype. However, we found the radio-resistance in the stem cell was only transient, and an apoptosis in p53-deficient hemopoietic stem cells, we made concentrated analysis including the end-labeling technique to detect double strand breaks of DNA. Results clearly showed that, according to the end-labeling for spleen colonies, the p53-deficiency showed rather higher incidence of apoptosis (30-50%) as compared with the wild-control (17%). Irradiation with 200cGy for the recipient mice two months after transplantation, showed an induction of higher incidence of hemopoietic malignancies, when the heterozygous marrow was repopulated, however, none of increase was observed in the recipient mice repopulated with the homozygous bone marrow. Clear difference between the hetero- and the homozygous in inducing hemopoietic malignancies with the 200cGy-radiation may be reflected by the different degree of delayed appearance of apoptosis during the development of the spleen colonies.