Shun-ichi Nihei

Upregulation of Vascular Extracellular Superoxide Dismutase in Patients With Acute Coronary Syndromes

Objective—We examined the vascular expression levels of extracellular superoxide dismutase (EC-SOD), a major antioxidant enzyme in the cardiovascular system, in patients with acute coronary syndromes. Methods and Results—Twenty-one consecutive patients with acute myocardial infarction (AMI), 14 patients with unstable angina, 11 patients with stable angina, and 20 control subjects were studied. The levels of vascular EC-SOD expression were assessed by the difference in plasma EC-SOD concentrations before and after intravenous heparan injection. In the patients with AMI, vascular EC-SOD expression (ng/mL) was significantly higher on day 1 after the onset of AMI (148±10) as compared with the control subjects (116±6, P <0.05). The vascular EC-SOD expression returned to the normal range on day 7 (104±8), and that level persisted thereafter. The vascular EC-SOD expression was also significantly higher in the patients with unstable angina (160±13) than in those with stable angina (122±10) or in the controls (116±6) (P <0.05 each). Moreover, in the patients with AMI, higher levels of vascular EC-SOD expression on day 1 were significantly associated with smaller myocardial infarct size (P <0.05). Conclusions—This is the first clinical demonstration showing that vascular EC-SOD may be upregulated in acute coronary syndromes in humans in vivo. EC-SOD may play an important protective role against increased oxidative stress during acute ischemic coronary events.

Oxidized low-density lipoprotein-induced apoptosis is attenuated by insulin-activated phosphatidylinositol 3-kinase/Akt through p38 mitogen-activated protein kinase.

1.u2002The aim of the present study was to investigate whether p38 mitogen‐activated protein kinase (p38 MAPK) is involved in oxidized low‐density lipoprotein (oxLDL)‐induced apoptosis of human umbilical vein endothelial cells (HUVECs). We also sought to determine whether this apoptosis is regulated by the phosphatidylinositol 3‐kinase (PI3K)/Akt pathway.

Evaluation of Improved Coronary Flow Velocity Reserve Using Transthoracic Doppler Echocardiography After Single LDL Apheresis

Abstract:u2002 The purpose of this study was to clarify whether coronary flow velocity reserve (CFVR), evaluated by adenosine 5′‐triphosphate‐induced hyperemia, is improved by single low‐density lipoprotein (LDL) apheresis. Lipid lowering therapy is known to improve endothelium‐dependent vasodilatation in forearm or coronary resistant vessels. However, few reports have studied the effect of acute LDL reduction on CFVR. Methods: Seven patients with familial hypercholesterolemia and significant coronary stenosis except in the left anterior descending artery (LAD) were enrolled in this study. Coronary flow velocity reserve was estimated before and after LDL apheresis using transthoracic Doppler echocardiography (TTDE), which detects the flow velocity at the distal site of the LAD. Although the averaged diastolic peak velocity (ADPV) during ATP‐induced hyperemia was similar before and after LDL apheresis, the ADPV at baseline decreased from 30.69 to 25.56u2003cm/s, resulting in an increased CFVR from 1.78 to 2.10 (Pu2003<u20030.001). Plasma bradykinin and 6u2003ketou2003PGF1α increased while fibrinogen and plasma viscosity decreased after apheresis. Single LDL apheresis improves CFVR according to TTDE analysis because of the decreasing ADPV at baseline, which is thought to be induced by epicardial coronary artery dilatation and improved microvessel function. This is the result of various factors, such as changes in plasma LDL cholesterol, bradykinin and PGI2 levels with LDL apheresis.