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SummaryAngiotensin converting enzyme inhibitors (ACE-I) have been reported to prevent the recurrence of cardiovascular events. The mechanism of this decrease, however, can not be completely explained by anti-hypertensive and anti-hypertrophic effects of ACE-I. To investigate the mechanism of this decrease, we studied the regulation of plasminogen activator inhibitor-1 (PAI-1), tissue type plasminogen activator (TPA), tissue factor (TF), and tissue factor pathway inhibitor (TFPI) by angiotensin II (Ang II) in cultured rat aortic endothelial cells. Ang II increased PAI-1 and TF mRNA expression without affecting that of TPA or TFPI. These inductions were accompanied by increases in PAI-1 and TF activities and were inhibited by a type 1 Ang II receptor antagonist. The results suggest that Ang II decreases the antithrombotic properties of endothelial cells which increases the chance of thrombosis. Thus, inhibition of the renin-angiotensin system may be beneficial to prevent thrombus formation in treatment of ischemic heart disease.

Protein S-K196E mutation as a genetic risk factor for deep vein thrombosis in Japanese patientsDeep vein thrombosis (DVT) is a multifactorial disease caused by interactions between acquired risk factors and coagulation abnormalities. 1 In whites, the factor V-Leiden and the prothrombin-20210GϾA are widely recognized as genetic risk factors for DVT. However, these 2 mutations are not present in Japanese populations, and little is known about the genetic risk factors for DVT in these populations. In this study, we evaluated the genetic contributions of 5 polymorphisms in Japanese DVT patients. The plasminogen-A620T mutation, formerly referred to as plasminogen-Tochigi, and the protein S-K196E mutation, formerly referred to as protein S-Tokushima, exhibited decreased activities of plasminogen and protein S despite normal antigen levels. 2-4 The ADAMTS13-P475S mutation exhibited low von Willebrand factorcleaving activity in vitro. 5 The factor XII-4CϾT substitution in the 5Ј-untranslated region, formerly referred to as 46CϾT, showed decreased plasma levels of both antigen and activity. 6 The plasminogen activator inhibitor-1 (PAI-1) 4G/5G polymorphism is related to in vitro differences in transcription activity. 7 We genotyped subjects for these 5 polymorphisms and compared their genotypic frequencies between 161 DVT patients and 3655 population-based controls. The protocol for this study was approved by the ethical review committee, and only those subjects who provided written informed consent for genetic analyses were included in this study. All participants of this study were Japanese. The controls were from a general population randomly selected from the residents of Suita City located in the second largest urban area in Japan (the Suita Study). 8 One hundred sixty-one DVT patients, 78 men and 83 women, were registered by the Study Group of Research on Measures for Intractable Diseases, working under the auspices of the Ministry of Health, Labor, and Welfare of Japan. Six centers (Tochigi, Tokyo, Nagoya, Kyoto, and 2 in Osaka) participated in this study. The patients' mean age was 49.5 years (range, 12-87 years) and their mean body mass index was 23.6 Ϯ 3.3. Thirteen percent of patients had a family history of thrombosis, and 16% of the patients had recurrent thrombosis.Of all the polymorphisms tested, only the frequency of protein S-K196E was statistically different between the 2 groups ( 2 ϭ 38.3, P Ͻ .001) ( Table 1). No other frequency differences were statistically significant. Two DVT patients were homozygous for the protein S-196E allele; however, no homozygotes were identified in the control group. One patient with the 196EE genotype first developed DVT following surgery at age 47, while the other patient developed DVT during pregnancy at age 32.The mutant protein S with the E allele has already been intensively studied as protein S-Tokushima. 11 The protein S mutant showed the reduced activated protein C cofactor activity compared with wild-type protein S, suggesting a direct link between the protein S-...

New Japanese diagnostic criteria were prepared for disseminated intravascular coagulation (DIC) in critically ill patients and their usefulness was compared with the criteria of the International Society of Thrombosis and Haemostasis (ISTH) and those of the Japan Ministry of Health and Welfare (JMHW). In a retrospective study of patients with platelet counts of less than 150 x10(3)/mL, 52 cases (33.3%), 66 cases (42.3%), and 101 cases (64.7%) were diagnosed as DIC by the ISTH, JMHW, and new Japanese DIC criteria, respectively. The DIC state as diagnosed by the new Japanese DIC criteria included both DIC states as diagnosed by ISTH or JMHW criteria. Some DIC states diagnosed by the JMHW criteria included those diagnosed by ISHT criteria but this was not universal. The mortality of DIC as diagnosed by the ISTH or JMHW criteria was markedly high, compared to that for DIC diagnosed by the new Japanese criteria. The mortality of patients without DIC by ISTH was also high when they were diagnosed as DIC by the new Japanese criteria. The frequency of DIC by each set of diagnostic criteria was significantly higher in patients with infection than in those without infection. The mortality of DIC by each set of diagnostic criteria was significantly higher in patients with infection than in those without infection, and the mortality of overt-DIC by ISTH diagnostic criteria was also high in patients without infection.

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