Papers - KAIKITA Koichi
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Komohara Y., Terasaki Y., Kaikita K., Suzuki H., Kodama T., Takeya M.
Developmental Dynamics 232 ( 1 ) 67 - 74 2005.1
Language：English Publishing type：Research paper (scientific journal) Publisher：Developmental Dynamics
Elimination of apoptotic cells is an important mechanism to maintain proper embryonal morphogenesis. The class A scavenger receptor type I, II (CD204), one of the major receptors expressed on macrophages, is a receptor actively involved in recognition and ingestion of apoptotic cells. To clarify the role of CD204 in embryonic morphogenesis, we performed immunohistochemical and immunoelectron microscopic studies using CD204-deficient mouse embryos. In control mice, almost all macrophages expressed CD204 from embryonic day 9.5 (E9.5). Phagocytes engulfing dead cells in the E13.5 interdigit region showed strong expression of CD204, indicating that CD204 was actively involved in apoptotic cell clearance. However, CD204 is not essential for the embryonic clearance of apoptotic cells, because CD204-deficient embryos developed normally without any retardation in footplate remodeling. Up-regulation of CD36 in CD204-deficient fetal macrophages suggested that CD36 substitutes for CD204 function. We also found that mesenchymal cells frequently engulfed apoptotic cells especially in early embryonal stages. These data suggest that CD204 is partially but not essentially involved in apoptotic cell clearance in embryogenesis. During early embryonal development, mesenchymal cells, rather than macrophages, play a major role in apoptotic cell clearance. © 2004 Wiley-Liss, Inc.
DOI： 10.1002/dvdy.20206
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Okuma T., Terasaki Y., Kaikita K., Kobayashi H., Kuziel W.A., Kawasuji M., Takeya M.
Journal of Pathology 204 ( 5 ) 594 - 604 2004.12
Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Pathology
Macrophage infiltration is implicated in various types of pulmonary fibrosis. One important pathogenetic process associated with pulmonary fibrosis is injury to basement membranes by matrix metalloproteinases (MMPs) that are produced mainly by macrophages. In this study, C-C chemokine receptor 2-deficient (CCR2-/-) mice were used to explore the relationship between macrophage infiltration and MMP activity in the pathogenesis of pulmonary fibrosis, using the bleomycin-induced model of this disease process. CCR2 is the main (if not only) receptor for monocyte chemoattractant protein-1/C-C chemokine ligand 2 (MCP-1/CCL2), which is a critical mediator of macrophage trafficking, and CCR2-/-mice demonstrate defective macrophage migration. Pulmonary fibrosis was induced in CCR2-/- and wild-type (CCR2+/+) mice by intratracheal instillation of bleomycin. No significant differences in the total protein concentration in bronchoalveolar lavage (BAL) fluid, or in the degree of histological lung inflammation, were observed in the two groups until day 7. Between days 3 and 21, however, BAL fluid from CCR2-/- mice contained fewer macrophages than BAL fluid from CCR2+/+ mice. Gelatin zymography of BAL fluid and in situ zymography revealed reduced gelatinolytic activity in CCR2-/-mice. Immunocytochemical staining showed weaker expression of MMP-2 and MMP-9 in macrophages in BAL fluid from CCR2-/- mice at day 3. Gelatin zymography of protein extracted from alveolar macrophages showed reduced gelatinolytic activity of MMP-2 and MMP-9 in CCR2-/- mice. At days 14 and 21, lung remodelling and the hydroxyproline content of lung tissues were significantly reduced in CCR2-/- mice. These results suggest that the CCL2/CCR2 functional pathway is involved in the pathogenesis of bleomycin-induced pulmonary fibrosis and that CCR2 deficiency may improve the outcome of this disease by regulating macrophage infiltration and macrophage-derived MMP-2 and MMP-9 production. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
DOI： 10.1002/path.1667
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Kaikita K., Hayasaki T., Okuma T., Kuziel W.A., Ogawa H., Takeya M.
American Journal of Pathology 165 ( 2 ) 439 - 447 2004.8
Authorship：Lead author, Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：American Journal of Pathology
A key component of cardiac remodeling after acute myocardial infarction (MI) is the inflammatory response, which modulates cardiac tissue repair. The purpose of this study was to investigate the relationship between the monocytic inflammatory response and left ventricular remodeling after MI using mice deficient in CC chemokine receptor 2 (CCR2), the primary receptor for the critical regulator of CC chemokine ligand 2. Immunohistochemical analysis revealed rapid infiltration of macrophages into infarcted tissue within 7 days in wild-type (WT) mice. However, this process was greatly impaired in CCR2-deficient (CCR2 ) mice. Echocardiography demonstrated beneficial effects of CCR2 deficiency on left ventricular remodeling at 7 and 28 days after MI. In situ zymography showed augmented gelatinolytic activity in WT mice within 7 days after MI, whereas gelatinolytic activity was barely detectable in CCR2 mice. Moreover, the distribution of gelatinolytic activity in serial sections was very similar to the distribution of macrophages rather than neutrophils. Expression of matrix metalloproteinases and tumor necrosis factor-α mRNAs was up-regulated in infarcted regions from WT mice compared to CCR2 mice at 3 days after MI. Direct inhibition of CCR2 functional pathway might contribute to the attenuation of left ventricular remodeling after MI. -/- -/- -/-
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Effects of Nicorandil on Endogenous Fibrinolytic Capacity in Patients with Coronary Artery Disease Reviewed
Sakamoto T., Kaikita K., Miyamoto S., Kojima S., Sugiyama S., Yoshimura M., Ogawa H.
Circulation Journal 68 ( 3 ) 232 - 235 2004.3
Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：Circulation Journal
Background: Nicorandil is a hybrid-type anti-anginal drug that combines a KATP channel opener and a nitric oxide donor. Recently the IONA study reported that nicorandil improves the prognosis of patients with stable angina pectoris. Methods and Results: To examine the effects of nicorandil on endogenous fibrinolysis, plasma concentrations of tissue-type plasminogen activator (t-PA) antigen, type-1 plasminogen activator inhibitor (PAI-1) antigen and PAI activity were measured in consecutive 11 patients (7 men and 4 women, mean age 63 years, ranges 41-84 years) with coronary artery disease. Nicorandil (15 mg/day) was administered orally to each patient for 2 weeks. Venous blood samples were obtained from each patient before and after the administration of the drug in the early morning before eating. There were no significant changes in the plasma concentrations of t-PA (12.4±1.9 to 9.8±1.5) or PAI-1 (26.3±3.9 to 21.5±4.9) antigens (ng/ml, mean±SEM) before and after nicorandil administration. On the other hand, the plasma activity of PAI (IU/ml, mean±SEM) decreased significantly after the treatment (12.9±3.2 to 5.6±1.9, p=0.039). Conclusions: It is well known that PAI activity determines the whole fibrinolytic capacity and oral administration of nicorandil decreased PAI activity in patients with coronary artery disease. This finding suggests that nicorandil improves the fibrinolytic capacity and may reduce the risk of coronary thrombus formation in such patients.
DOI： 10.1253/circj.68.232
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Suzuki S., Sugiyama S., Usuku H., Hirai N., Kaikita K., Sakashita N., Sakamoto T., Yoshimura M., Ogawa H.
Internal Medicine 43 ( 3 ) 199 - 203 2004.3
Language：English Publishing type：Research paper (scientific journal) Publisher：Internal Medicine
We report a 67-year-old Japanese man who presented with worsening heart failure with asymptomatically transient ischemic ST-segment depression. Left ventriculography showed diffuse hypokinesis; asymptomatic coronary artery spasm was evoked by the acetylcholine provocation test. Endomyocardial biopsy exhibited hypertrophic cardiomyocytes and scattered microscopic focal myocardial necrosis with amyloid-deposition. Transient ST-segment depression improved after treatment with a calcium antagonist, but cardiac contraction was still impaired. We hypothesize that asymptomatic coronary spasm may cause irreversible cardiac damage and heart failure with amyloid-deposition; the presence or absence of coronary spasm in heart failure patients should be clarified in order to determine therapeutic strategy.
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KAIKITA K
J Mol Cell Cardiol 34 ( 6 ) 617 - 627 2002.6
Authorship：Lead author Language：English Publishing type：Research paper (scientific journal)
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KAIKITA K
Circulation 104 ( 7 ) 839 - 844 2001.8
Authorship：Lead author Language：English Publishing type：Research paper (scientific journal)
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Soejima H., Ogawa H., Suefuji H., Kaikita K., Takazoe K., Miyamoto S., Kajiwara I., Shimomura H., Sakamoto T., Yoshimura M., Nakamura S.
American Journal of Cardiology 87 ( 12 ) 1408 - 1411 2001.6
Language：English Publishing type：Research paper (scientific journal) Publisher：American Journal of Cardiology
In conclusion, this study demonstrates that losartan and enalapril improved hypercoagulability in patients with AMI associated with improvement in impaired fibrinolysis.
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Ogawa H., Sakamoto T., Nishiyama K., Soejima H., Kaikita K., Takazoe K., Miyamoto S., Kugiyama K., Yoshimura M., Yasue H.
Japanese Circulation Journal 64 ( 3 ) 170 - 176 2000.3
Language：English Publishing type：Research paper (scientific journal) Publisher：Japanese Circulation Journal
The cell surface expression of intercellular adhesion molecule-1 (ICAM- 1) is upregulated following activation during inflammatory responses, mediating both cell migration and activation. The involvement of inflammation in unstable angina is suggested by the presence of activated circulating leukocytes. To examine whether plasma soluble ICAM-1 (sICAM-1) levels increase in the coronary circulation of patients with coronary organic stenosis and coronary spasm, plasma sICAM-1 levels were measured in the coronary sinus (CS) and the aortic root (Ao) simultaneously in 10 patients with 90% or more coronary narrowing and coronary spasm (coronary spastic angina (CSA) with organic stenosis), in 11 patients with coronary spasm and no significant coronary narrowing (CSA without organic stenosis), in 16 patients with stable exertional angina, and in 13 control subjects. The plasma sICAM-1 levels (ng/ml) in the CS increased in CSA with organic stenosis (230±26) as compared with CSA without organic stenosis (158±14), stable exertional angina (130±9) and control subjects (121±10) (p<0.01). The levels in the Ao also increased in CSA with organic stenosis (208±24) as compared with CSA without organic stenosis (149±13), stable exertional angina (130±11) and control subjects (121±10) (p<0.01). Furthermore, the plasma sICAM-1 levels were higher in the CS than in the Ao only in CSA with organic sterosis. These results suggest that activation of leukocytes occurs through the induction of ICAM-1 in the coronary circulation in the patients with CSA with organic stenosis.
DOI： 10.1253/jcj.64.170
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Difference in fibrinolytic activity between multivessel coronary spasm and one-vessel coronary spasm Reviewed
Ogawa H., Suefuji H., Takazoe K., Soejima H., Sakamoto T., Miyamoto S., Kaikita K., Yoshimura M., Kugiyama K., Yasue H.
American Journal of Cardiology 85 ( 1 ) 98 - 101 2000.1
Language：English Publishing type：Research paper (scientific journal) Publisher：American Journal of Cardiology
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Increased plasma level of soluble E-selectin in acute myocardial infarction Reviewed
Suefuji H., Ogawa H., Yasue H., Sakamoto T., Miyao Y., Kaikita K., Soejima H., Misumi K., Miyamoto S., Kataoka K.
American Heart Journal 140 ( 2 ) 243 - 248 2000
Language：English Publishing type：Research paper (scientific journal) Publisher：American Heart Journal
Background: E-selectin, also known as endothelial cell leukocyte adhesion molecule-1, is a member of the selectin family of adhesion molecules and is expressed on vascular endothelial cells in inflammatory reactions. The induction of surface E-selectin expression by endothelial cells is considered a marker of activation. Methods and Results: We examined the plasma soluble E-selectin (sE-selectin) level in 41 patients within 6 hours after the onset of acute myocardial infarction (AMI) and in 37 patients with stable exertional angina and 27 control patients. Blood samples were obtained on admission, after reperfusion therapy, and at 4 hours, 8 hours, 12 hours, 24 hours, 48 hours, 3 days, 5 days, 1 week, and 2 weeks after admission in the AMI group. In this group, 21 patients had a history of prodromal unstable angina before infarction and 20 had sudden onset of infarction. The plasma sE-selectin level (ng/mL) on admission was higher in the AMI group than in the stable exertional angina group and control group (38.5 ± 3.1 vs 28.5 ± 1.5, P < .01, 26.0 ± 1.8, P < .01, respectively). In addition, plasma sE-selectin levels were higher in the patients with AMI with prodromal unstable angina than in those with a sudden onset of infarction on admission (44.7 ± 5.4 vs 32.0 ± 2.1, P < .05). The plasma sE-selectin level decreased slowly during the chronic phase both in patients with AMI with prodromal unstable angina (from 44.7 ± 5.4 to 33.8 ± 3.4, P < .01) and those with a sudden onset of infarction (from 32.0 ± 2.1 to 24.9 ± 2.4, P <.01). Conclusions: These results suggest that an increase of sE-selectin may reflect enhanced endothelial cell activation in patients with AMI. The higher sE-selectin level in patients with AMI with prodromal unstable angina may have been associated with repeated episodes of myocardial ischemia and reperfusion.
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Soejima H., Ogawa H., Yasue H., Kaikita K., Takazoe K., Nishiyama K., Misumi K., Miyamoto S., Yoshimura M., Kugiyama K., Nakamura S., Tsuji I.
Journal of the American College of Cardiology 34 ( 4 ) 983 - 988 1999.10
Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of the American College of Cardiology
OBJECTIVES: We investigated the effects of enalapril therapy on plasma tissue factor (TF), tissue factor pathway inhibitor (TFPI) and monocyte chemoattractant protein-1 (MCP-1) levels in patients with acute myocardial infarction. BACKGROUND: Macrophages express TF in human coronary atherosclerotic plaques. Both TF and TFPI are major regulators of coagulation and thrombosis. Monocyte chemoattractant protein-1 is a monocyte and macrophage chemotactic and activating factor. METHODS: In a randomized, double-blind, placebo-controlled study beginning about two weeks after myocardial infarction, 16 patients received four weeks of placebo (placebo group) and another 16 patients received four weeks of enalapril 5 mg daily therapy (enalapril group). We performed blood sampling after administration of the doses. RESULTS: There were no significant differences in the serum angiotensin-converting enzyme (ACE) activity, plasma TF, free TFPI or MCP-1 levels before administration between the enalapril and placebo groups. In the enalapril group, ACE activity (IU/liter) (14.0 before, 5.2 on day 3, 5.8 on day 7, 6.3 on day 28), TF levels (pg/ml) (223, 203, 182, 178) and MCP-1 levels (pg/ml) (919, 789, 790, 803) significantly decreased by day 28. However, the free TFPI levels (ng/ml) (28.2, 26.5, 26.8, 28.4) did not change. These four variables were unchanged during the study period in the placebo group. CONCLUSIONS: This study demonstrated that administration of enalapril reduces the increased procoagulant activity in patients with myocardial infarction associated with inhibition of the activation and accumulation of macrophages and monocytes.
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Takazoe K., Ogawa H., Yasue H., Sakamoto T., Oshima S., Arai H., Moriyama Y., Shimomura H., Hirai N., Kaikita K., Soejima H., Misumi K., Hosoda K.
Thrombosis Research 95 ( 1 ) 37 - 47 1999.7
Language：English Publishing type：Research paper (scientific journal) Publisher：Thrombosis Research
Protein C is one of the most important antithrombotic components. After activation by the thrombin-thrombomodulin complex on endothelial cells, activated protein C (APC) inactivates factors Va and VIIIa, which leads to the inhibition of thrombin formation. We examined the association of plasma levels of APC with the responsiveness to coronary thrombolytic therapy of the infarct-related coronary artery in patients with acute myocardial infarction (AMI). Plasma levels of APC, thrombin-antithrombin III complex (TAT), and plasminogen activator inhibitor (PAI) activity were measured in 32 consecutive AMI patients who underwent coronary angiography followed by thrombolytic therapy, and compared to the measurements in 23 control subjects. On admission, APC levels (ng/mL) were significantly elevated in patients with AMI, as compared with controls (2.5±0.4 vs. 1.2±0.2, 1.3±0.2, respectively, p<0.01). At discharge, plasma levels in AMI patients decline to values not significantly different from those in controls. (1.2±0.2, 1.3±0.2, respectively). TAT levels (ng/mL) were different among the groups in a fashion similar to that of APC (14.1±3.1 on admission vs. 3.3±0.4 at discharge, 1.8±0.1 in the control subjects, respectively, p<0.01). PAI activity levels (IU/mL) were higher on admission than at discharge and higher than the control subjects (19.7±1.8 vs. 10.5±1.0, 5.4±0.7, respectively, p<0.01). Thirty-two patients with AMI were classified into two groups according to the results of thrombolysis: the success group (24 patients) and the failure group (eight patients). APC levels were higher in the failure group than in the success group (5.1±0.7 vs. 1.6±0.2, p<0.01). TAT levels were also higher in the failure group than in the success group (30.8±9.6 vs. 8.6±1.7, p<0.01). PAI activity levels (IU/mL) were lower in the failure group than in the success group (13.5±3.1 vs. 21.7±2.1, p<0.05). There were correlations between APC and TAT levels both on admission (r=0.75, p<0.0001) and at discharge (r=0.71, p<0.0001). Elevated APC was thought to correlate with increased thrombin generation in patients with AMI. This study demonstrated that there was a significant relation between plasma APC level and the responsiveness to thrombolytic therapy of the impact artery. This study may also indicate that increased thrombin generation is a cause of the resistance to thrombolytic therapy.
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Co-localization of tissue factor and tissue factor pathway inhibitor in coronary atherosclerosis Reviewed
Kaikita K., Takeya M., Ogawa H., Suefuji H., Yasue H., Takahashi K.
Journal of Pathology 188 ( 2 ) 180 - 188 1999.6
Authorship：Lead author Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Pathology
Tissue factor (TF) initiates the extrinsic pathway of blood coagulation by acting as a cofactor for Factor VII. Inhibition of the Factor VIIa-TF complex is mediated by the tissue factor pathway inhibitor (TFPI), which is a serine protease inhibitor with three Kunitz-type domains. The localization of TF and TFPI protein has been examined immunohistochemically in various atherosclerotic lesions of coronary arteries from 22 autopsy cases and their messenger RNA expression has been confirmed by reverse transcription- polymerase chain reaction. Four types of atherosclerotic lesion (types I, II, III, and IV) were classified according to the method described by Stary et al. TF and TFPI were localized in endothelial cells, macrophages, macrophage- derived foam cells, and smooth muscle cells in the intimal lesions, medial smooth muscle cells, and endothelial cells of the microvessels in the adventitia. Immunohistochemical double staining revealed the co-localization of TF and TFPI in the endothelial cells and macrophages in four types of atherosclerotic lesions. In type III and IV lesions, the number of TF- and TFPI-positive cells was increased, accompanied by extracellular localization of TF and TFPI in the lipid core of atherosclerotic plaques. Fibrin deposition was found around TF- and TFPI-positive macrophages and in the lipid core of atherosclerotic plaques. TF and TFPI messenger RNA were detected more frequently in coronary arteries with type III and IV lesions than in those with type I and II lesions. The co-localization of TF and TFPI was demonstrated in various atherosclerotic lesions of coronary arteries and was shown to be intimately related to fibrin deposition in advanced atherosclerotic plaques. The co-localization of TF and TFPI may thus be closely associated with thrombogenicity in atherosclerotic lesions of coronary arteries.
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Soejima H., Ogawa H., Yasue H., Kaikita K., Nishiyama K., Misumi K., Takazoe K., Miyao Y., Yoshimura M., Kugiyama K., Nakamura S., Tsuji I., Kumeda K.
Circulation 99 ( 22 ) 2908 - 2913 1999.6
Language：English Publishing type：Research paper (scientific journal) Publisher：Circulation
Background - This study was designed to evaluate the plasma levels of tissue factor (TF) and tissue factor pathway inhibitor (TFPI) in patients with unstable angina and investigate whether there is a relationship between these levels and unfavorable outcome. Methods and Results - The plasma TF and free TFPI antigen levels were determined in plasma samples taken from 51 patients with unstable angina, 56 with stable exertional angina, and 55 with chest pain syndrome. The plasma TF and free TFPI antigen levels were higher in the unstable angina group than in the stable exertional angina and chest pain syndrome group. There was a good correlation between TF and TFPI. We established borderline as maximum level in the patients with chest pain syndrome. Seven patients (of the 22 in the high TF group) required revascularization to control their unstable angina during in-hospital stay. On the other hand, only 1 of the 29 patients in the low TF group required myocardial revascularization. Four patients of the 14 patients in the high free TFPI group required myocardial revascularization during in-hospital stay, and 4 of the 37 patients in the low free TFPI group required myocardial revascularization. We compared the TF and free TFPI levels between the cardiac event (+) group and cardiac event (-) group. TF levels were significantly higher in the cardiac event (+) group than in the cardiac event (-) group. Conclusions - We have demonstrated that not only the plasma TF levels but also the plasma-free TFPI levels are elevated in patients with unstable angina. Patients with unstable angina and heightened TF and free TFPI are at increased risk for unfavorable outcomes. The heightened TF level was a more important predictor in patients with unstable angina.
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Ogawa H., Yasue H., Miyao Y., Sakamoto T., Soejima H., Nishiyama K., Kaikita K., Suefuji H., Misumi K., Takazoe K., Kugiyama K., Yoshimura M.
American Journal of Cardiology 83 ( 1 ) 38 - 42 1999.1
Language：English Publishing type：Research paper (scientific journal) Publisher：American Journal of Cardiology
It has been suggested that active inflammation plays an important role in the pathogenesis of acute coronary syndromes, including unstable angina. Intracellular adhesion molecule-1 (ICAM-1) is a major ligand on the endothelial cells for adherence of the activated polymorphonuclear leukocytes. Recently, it has been demonstrated that the soluble form of ICAM- 1 has been detected in human serum and has been increased in many other inflammatory or autoimmune disorders. To evaluate the involvement of ICAM-1 in unstable angina, we examined plasma soluble ICAM-1 (sICAM-I) levels in coronary circulation. The plasma sICAM-1 levels in the coronary sinus and aortic root were simultaneously examined in 20 patients with unstable angina, 19 patients with stable exertional angina, and 16 control subjects. The plasma levels of sICAM-1 were measured by enzyme-linked immunosorbent assay. The mean plasma sICAM-1 levels (nanograms per milliliter) both in the coronary sinus and aortic root were significantly higher (p <0.01) in patients with unstable angina than in those with stable exertional angina and in control subjects (217 ± 14 vs 126 ± 8; 120 ± 10 in the coronary sinus, 202 ± 13 vs 125 ± 9; 123 ± 10 in the aortic root). Furthermore, the mean value was higher in the coronary sinus than in the aortic root in patients with unstable angina. There were no significant differences in the values between in the coronary sinus and aortic root in patients with stable exertional angina and control subjects. Thus, sICAM-1 release is increased, especially in coronary circulation in unstable angina.
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Soejima H., Ogawa H., Yasue H., Nishiyama K., Kaikita K., Misumi K., Takazoe K., Kugiyama K., Tsuji I., Kumeda K., Nakamura S.
Thrombosis Research 93 ( 1 ) 17 - 25 1999.1
Language：English Publishing type：Research paper (scientific journal) Publisher：Thrombosis Research
The hypercoagulability is associated with expression of tissue factor in patients with angina. Tissue factor pathway inhibitor regulates the extrinsic coagulation pathway mediated by tissue factor. Plasma samples were obtained from 14 patients with angina pectoris and 9 with chest pain syndrome before and 5, 30, 60, and 120 minutes after administration of heparin (50 IU/kg). The tissue factor and prothrombin fragment 1+2 levels before administration were elevated in patients with angina pectoris and were reduced to the levels of chest pain syndrome after the administration. The free tissue factor pathway inhibitor levels after the administration were higher in patients with angina pectoris than in patients with chest pain syndrome. Plasma tissue factor pathway inhibitor levels correlated positively with plasma tissue factor and prothrombin fragment 1+2 levels. We showed that plasma-free TFPI levels after administration of heparin, which may indicate endothelial cell associated TFPI levels, increased in patients with angina pectoris compared with patients with chest pain syndrome. Increased endothelial cell associated TFPI was associated with hypercoagulability in patients with angina pectoris. These may help to explain the reduction in thrombotic risk associated with the use of heparin.
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Serial changes in plasma levels of soluble P-selectin in patients with acute myocardial infarction Reviewed
Shimomura H., Ogawa H., Arai H., Moriyama Y., Takazoe K., Hirai N., Kaikita K., Hirashima O., Misumi K., Soejima H., Nishiyama K., Yasue H.
American Journal of Cardiology 81 ( 4 ) 397 - 400 1998.2
Language：English Publishing type：Research paper (scientific journal) Publisher：American Journal of Cardiology
The present study examines whether an acute inflammatory response occurs during acute myocardial infarction (AMI) by measuring soluble P-selectin levels. We examined plasma soluble P-selectin levels in 16 consecutive patients with AMI, in 15 patients with angina, and in 13 control subjects with chest pain but normal coronary arteries and no coronary spasm. In patients with AMI, blood samples were obtained immediately after admission and at 1, 4, 24, and 48 hours, and 1 week after initiation of reperfusion therapy. The plasma soluble P-selectin levels were significantly higher in the AMI group on admission than in the other 2 groups (83 ± 13 ng/ml, p <0.01). The plasma soluble P-selectin levels at baseline were not significantly different between the angina and control groups (28 ± 4 vs 24 ± 5 ng/ml, p = NS). Plasma soluble P-selectin levels reached their peak significantly at 4 hours after initiation of the reperfusion therapy in patients with AMI. The peak level was significantly higher than the level on admission (115 ± 17 vs 83 ± 13 ng/ml, p <0.05). The plasma soluble P- selectin levels were higher in the AMI group than in the angina and control groups over the time course (p <0.01). Our data indicate that the plasma soluble P-selectin levels are increased in patients with AMI, and that the levels are increases after reperfusion therapy more than before reperfusion. We suggest that the increase in the plasma soluble P-selectin levels may be caused by the activation of endothelial cells and platelets after myocardial ischemia and reperfusion during AMI.
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Moriyama Y., Ogawa H., Oshima S., Takazoe K., Honda Y., Hirashima O., Arai H., Sakamoto T., Sumida H., Suefuji H., Kaikita K., Yasue H.
Japanese Circulation Journal 61 ( 4 ) 308 - 314 1997
Language：English Publishing type：Research paper (scientific journal) Publisher：Japanese Circulation Journal
Recent clinical trials have demonstrated that the administration of angiotensin-converting enzyme (ACE) inhibitors to patients with myocardial infarction reduces the incidence of recurrent myocardial infarction. It has also been reported that an elevated level of plasminogen activator inhibitor (PAI) appears to constitute a marker of the risk of recurrent coronary thrombosis. To determine whether the ACE inhibitor captopril reduces plasma PAI inhibitor activity, we measured changes in plasma PAI activity (IU/ml), tissue plasminogen activator (t-PA) antigen (ng/ml), and serum ACE activity (IU/L) in 14 survivors of myocardial infarction receiving captopril therapy (37.5 mg daily) and compared them with the values in 15 placebo-treated patients chosen at random. Blood sampling was performed at 07.00 h. In the captopril-treated group, serum ACE activity decreased significantly, from 14.0 + 0.8 to 11.5 + 1.2 IU/L 24 h after captopril therapy (p<0.01), and those of PAI activity and t-PA antigen also decreased significantly - from 11.9 + 2.8 to 5.5+2.2 IU/ml (p<0.02) and from 9.9 + 1.0 to 7.5 + 0.9 ng/ml (p<0.05), respectively 48 h after captopril therapy. However, the levels of ACE activity, PAI activity, and t-PA antigen remained unchanged during the study period in the placebo group. Thus, our data indicate that the administration of captopril to patients with acute myocardial infarction may result in a reduced frequency of recurrent coronary thrombosis by increasing fibrinolytic capacity. © 1997, The Japanese Circulation Society. All rights reserved.
DOI： 10.1253/jcj.61.308
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Kaikita K., Ogawa H., Yasue H., Sakamoto T., Miyao Y., Suefuji H., Soejima H., Tayama S., Hayasaki K., Honda T., Kamijikkoku S.
Japanese Circulation Journal 61 ( 9 ) 741 - 748 1997
Authorship：Lead author Language：English Publishing type：Research paper (scientific journal) Publisher：Japanese Circulation Journal
Intercellular adhesion molecule-1 (ICAM-1) is a major ligand for 2 members of the CD18 family of leukocyte integrin adhesion molecules and mediates adhesion between leukocytes and stimulated endothelial cells. We examined plasma soluble ICAM-1 (sICAM-1) levels in 30 patients with acute myocardial infarction (AMI) within 6 h of symptom onset, 21 patients with unstable angina (UA), 35 patients with stable exertional angina (SEA) and 21 control subjects. Plasma sICAM-1 levels (ng/ml) were significantly higher in both the acute and chronic phases of AMI and in the UA group than in the SEA and the control groups (195+14, 198+16 in the acute and chronic phases of AMI, 188+11 in the UA group vs 142+7 in the SEA group, 141 + 10 in the control group, p<0.01). Plasma sICAM-1 levels were significantly higher in AMI patients when preceded by unstable angina than when not preceded by unstable angina at any point over the time course except 1 week after admission (p<0.01 vs admission, 12 h, 2 days, 3 days, 5 days, 2 weeks, 3 weeks. P<0.05 vs 24 h). These results suggest that the increase in sICAM-1 is associated with repeated episodes of myocardial ischemia and reperfusion not leading to myocardial necrosis. The increase in sICAM-1 may play an important role as an inflammatory component in the pathogenesis of the ischemic myocardium. © 1997, The Japanese Circulation Society. All rights reserved.
DOI： 10.1253/jcj.61.741