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The impact of the metabolic syndrome on the survival in patients with acute myocardial infarction
The 8th Annual Scientific Meeting
•
JHFS
S159
O-017
O-019
The Impact of the Metabolic Syndrome on the Survival in Patients with Acute Myocardial Infarction TAKENO MASAYOSHI, YASUDA SATOSHI, OTSUKA YORITAKA, KATAOKA YU, MORII ISAO, KAWAMURA ATSUSHI, MIYAZAKI SYUNICHI Cardiology, National Cardiovascular Center, Osaka, Japan
The Ubiquitin-Proteasome System is Enhanced in Degenerating Cardiomyocytes of Dilated Cardiomyopathy OTSUKA KOJI1, HIROAKI SIMOMURA1, TERASAKI FUMIO1, TSUKADA BIN1, KITAURA YASUSHI1, HORII TAIKO2, ISOMURA TADASHI2, SUMA HISAYOSHI2 1 Third Division, Department of internal medicine, Osaka Medical College, Osaka, Japan, 2Hayama Heart Center, kanagawa, Japan
Background: Population-based studies demonstrated that metabolic syndrome is associated with cardiovascular diseases. However, in patients with acute myocardial infarction (AMI), the impact of metabolic syndrome on survival is unclear. Methods: We evaluated the 461 consecutive AMI patients. On the basis of National Cholesterol Education Program Adult Treatment Panel III criteria, metabolic syndrome was defined as at least 3 of the following 5 component conditions; insulin resistance, obesity, hypertriglyceridemia, low HDL cholesterol and hypertension. Results: 138 patients (30%) showed metabolic syndrome. During follow-up mean 19 months, mortality of metabolic syndrome was significant lower (p ⫽ 0.014, figure). Furthermore, even after adjustment of age and sex, metabolic syndrome was associated with death (relative risk 2.2; 95% confidence interval, 1.1 to 4.5, P ⫽ 0.02). Conclusions: Metabolic syndrome is an important predictor for mortality following AMI.
To maintain intracellular homeostasis against cellular stresses, proteins are not only synthesized but also degraded by proteolytic mechanisms. The ubiquitin (Ub)-proteasome system is the most important mechanism to select and digest damaged intracellular proteins. However, it is still unclear how the Ub-proteasome system plays a role in the failing heart. To elucidate the expressions of Ub and proteasomes in the myocardium of dilated cardiomyopathy (DCM), myocardial tissue obtained from nineteen DCM patients at the left ventriculoplasty was studied. Four normal autopsied hearts served as control. Immunohistochemistry revealed that both Ub and proteasomes were very weak in controls and in less degenerated cardiomyocytes of DCM hearts. On the other hand, their expressions were markedly enhanced in vesicles accumulated adjacent to nuclei, periphery of large vacuoles, hyaline materials and disorganized cytoplasm of degenerated cardiomyocytes. The quantitative analysis of percent area showed that expression of Ub and proteasome were statistically higher in DCM hearts than in normal controls. We propose that the Ub-proteasome system may be protectively enhanced to disorganize damaged proteins and reduce their toxicity. However, it is also possible that the Ub-proteasome system, when its expression is massive, may associate with cytoplasmic degeneration preceding cell death. In conclusion, proteolysis by the Ub-proteasome system is enhanced under the condition where cardiomyocyte degeneration is processing in DCM hearts.
O-020 Autophagic Cell Death Affects Myocardial Damage in the UM-X7.1 Strain Cardiomyopathic Hamster MIYATA SHUSAKU1, GENZOU TAKEMURA1, YUKINORI KAWASE1, HIDESHI OKADA1, YIWEN LI1, RUMI MARUYAMA1, MASAYASU ESAKI1, SHINYA MINATOGUCHI1, TAKAKO FUJIWARA2, HISAYOSHI FUJIWARA1 1 Department of Cardiology, Gifu University, Graduate School of Medicine, Gifu, Japan, 2Department of Food Science, Kyoto Women’s University, Kyoto, Japan
O-018 Intracoronary Thrombus Aspiration in Patients with Acute Myocardial Ischemia, Does It Make Sense? KASAHARA YOICHIRO, KAWAMURA ATSUSHI, TAKENO MASAYOSHI, KATAOKA YU, MIYAMOTO SHINZO, YASUDA SATOSHI, MORII ISAO, MIYAZAKI SHUNICHI Division of Cardiology, National Cardiovascular Center, Osaka, Japan Purpose: It has been reported by basic study that intracoronary thrombus has relation to restenosis after perctaneous coronary intervention (PCI). The aim of this retrospective study is to evaluate the efficacy of intracoronary thrombus aspiration (ITA) in patients with acute myocardial infarction (AMI). Method: Between April 1999 and March 2003, emergent PCI was performed within 24 hours after the onset of myocardial infarction in 436 consecutive patients. We categorized them before (Group B) or after (Group A) introduction of ITA. Additionally, we analyzed the 59 patients who had documented intracoronary thrombus by coronary angiogram from the group B (Subgroup T), and the 54 patients who underwent ITA (Subgroup ITA). Results: In both group B and A, clinical baseline characteristics were similar, and there were no significant differences in the incidence of slow flow or no reflow phenomenon, use of IABP for residual thrombus, in-hospital death, and long-term outcome (Left ventricular ejection fraction and restenosis). In both subgroups, there were also no significant differences in the same parameters. Furthermore, the incidence of restenosis was not different between subgroup ITA and T (15 vs. 20%, p ⫽ 0.24). Conclusion: Nothing of parameters was different between two groups. The use of ITA seems to have no clinical benefit. There is a possibility that ITA reduces the incidence of restenosis in AMI with significant intracoronary thrombus.
The UM-X7.1 hamster (UM-X) is known as the animal model of cardiomyopathy. The hearts shows numerous foci of cardiomyocyte dropout, but the mode of cardiomyocyte death has not been well characterized. So, we investigated involvement of autophagic cardiomyocyte death in this model.We used male UM-X at the age of 10, 20, and 30week (n ⫽ 8 each), and age-matched male Golden hamsters (Golden) (n ⫽ 8 each) as the control. We performed histological examination (HE, MT, Evans blue, and TUNEL), immunohistochemistry for cathepsin D, electron microscopy (EM), and EM-TUNEL. Compared with Golden, UM-X showed more frequent Evans blue-positive cardiomyocytes with increased permeability of the plasma membrane (Golden, 0 ⫾ 0% vs. UM-X, 0.62 ⫾ 0.48%, p ⬍ 0.05). Similarly, the number of cathepsin D-positive cardiomyocytes in UM-X was greater than that in Golden (Golden, 0.7 ⫾ 0.52% vs. UM-X, 9.6 ⫾ 6.8%, p ⬍ 0.05). Most of the Evans blue-positive cardiomyocytes in UM-X were also positive for cathepsin D. Most importantly, cardiomyocytes were found in hearts of UM-X under electron microscopy, that showed autophagic degeneration with various grades; the autophagic vacuoles contained degraded mitochondria and myelin-like figures. Although the number of TUNEL positive cells in UM-X was greater than that in Golden, those cells were not apoptotic according to electron microscopic TUNEL assay.Degeneration and cell death of UM-X cardiomyocytes are caused by not apotosis, but autophagy.
•
JHFS
S159
O-017
O-019
The Impact of the Metabolic Syndrome on the Survival in Patients with Acute Myocardial Infarction TAKENO MASAYOSHI, YASUDA SATOSHI, OTSUKA YORITAKA, KATAOKA YU, MORII ISAO, KAWAMURA ATSUSHI, MIYAZAKI SYUNICHI Cardiology, National Cardiovascular Center, Osaka, Japan
The Ubiquitin-Proteasome System is Enhanced in Degenerating Cardiomyocytes of Dilated Cardiomyopathy OTSUKA KOJI1, HIROAKI SIMOMURA1, TERASAKI FUMIO1, TSUKADA BIN1, KITAURA YASUSHI1, HORII TAIKO2, ISOMURA TADASHI2, SUMA HISAYOSHI2 1 Third Division, Department of internal medicine, Osaka Medical College, Osaka, Japan, 2Hayama Heart Center, kanagawa, Japan
Background: Population-based studies demonstrated that metabolic syndrome is associated with cardiovascular diseases. However, in patients with acute myocardial infarction (AMI), the impact of metabolic syndrome on survival is unclear. Methods: We evaluated the 461 consecutive AMI patients. On the basis of National Cholesterol Education Program Adult Treatment Panel III criteria, metabolic syndrome was defined as at least 3 of the following 5 component conditions; insulin resistance, obesity, hypertriglyceridemia, low HDL cholesterol and hypertension. Results: 138 patients (30%) showed metabolic syndrome. During follow-up mean 19 months, mortality of metabolic syndrome was significant lower (p ⫽ 0.014, figure). Furthermore, even after adjustment of age and sex, metabolic syndrome was associated with death (relative risk 2.2; 95% confidence interval, 1.1 to 4.5, P ⫽ 0.02). Conclusions: Metabolic syndrome is an important predictor for mortality following AMI.
To maintain intracellular homeostasis against cellular stresses, proteins are not only synthesized but also degraded by proteolytic mechanisms. The ubiquitin (Ub)-proteasome system is the most important mechanism to select and digest damaged intracellular proteins. However, it is still unclear how the Ub-proteasome system plays a role in the failing heart. To elucidate the expressions of Ub and proteasomes in the myocardium of dilated cardiomyopathy (DCM), myocardial tissue obtained from nineteen DCM patients at the left ventriculoplasty was studied. Four normal autopsied hearts served as control. Immunohistochemistry revealed that both Ub and proteasomes were very weak in controls and in less degenerated cardiomyocytes of DCM hearts. On the other hand, their expressions were markedly enhanced in vesicles accumulated adjacent to nuclei, periphery of large vacuoles, hyaline materials and disorganized cytoplasm of degenerated cardiomyocytes. The quantitative analysis of percent area showed that expression of Ub and proteasome were statistically higher in DCM hearts than in normal controls. We propose that the Ub-proteasome system may be protectively enhanced to disorganize damaged proteins and reduce their toxicity. However, it is also possible that the Ub-proteasome system, when its expression is massive, may associate with cytoplasmic degeneration preceding cell death. In conclusion, proteolysis by the Ub-proteasome system is enhanced under the condition where cardiomyocyte degeneration is processing in DCM hearts.
O-020 Autophagic Cell Death Affects Myocardial Damage in the UM-X7.1 Strain Cardiomyopathic Hamster MIYATA SHUSAKU1, GENZOU TAKEMURA1, YUKINORI KAWASE1, HIDESHI OKADA1, YIWEN LI1, RUMI MARUYAMA1, MASAYASU ESAKI1, SHINYA MINATOGUCHI1, TAKAKO FUJIWARA2, HISAYOSHI FUJIWARA1 1 Department of Cardiology, Gifu University, Graduate School of Medicine, Gifu, Japan, 2Department of Food Science, Kyoto Women’s University, Kyoto, Japan
O-018 Intracoronary Thrombus Aspiration in Patients with Acute Myocardial Ischemia, Does It Make Sense? KASAHARA YOICHIRO, KAWAMURA ATSUSHI, TAKENO MASAYOSHI, KATAOKA YU, MIYAMOTO SHINZO, YASUDA SATOSHI, MORII ISAO, MIYAZAKI SHUNICHI Division of Cardiology, National Cardiovascular Center, Osaka, Japan Purpose: It has been reported by basic study that intracoronary thrombus has relation to restenosis after perctaneous coronary intervention (PCI). The aim of this retrospective study is to evaluate the efficacy of intracoronary thrombus aspiration (ITA) in patients with acute myocardial infarction (AMI). Method: Between April 1999 and March 2003, emergent PCI was performed within 24 hours after the onset of myocardial infarction in 436 consecutive patients. We categorized them before (Group B) or after (Group A) introduction of ITA. Additionally, we analyzed the 59 patients who had documented intracoronary thrombus by coronary angiogram from the group B (Subgroup T), and the 54 patients who underwent ITA (Subgroup ITA). Results: In both group B and A, clinical baseline characteristics were similar, and there were no significant differences in the incidence of slow flow or no reflow phenomenon, use of IABP for residual thrombus, in-hospital death, and long-term outcome (Left ventricular ejection fraction and restenosis). In both subgroups, there were also no significant differences in the same parameters. Furthermore, the incidence of restenosis was not different between subgroup ITA and T (15 vs. 20%, p ⫽ 0.24). Conclusion: Nothing of parameters was different between two groups. The use of ITA seems to have no clinical benefit. There is a possibility that ITA reduces the incidence of restenosis in AMI with significant intracoronary thrombus.
The UM-X7.1 hamster (UM-X) is known as the animal model of cardiomyopathy. The hearts shows numerous foci of cardiomyocyte dropout, but the mode of cardiomyocyte death has not been well characterized. So, we investigated involvement of autophagic cardiomyocyte death in this model.We used male UM-X at the age of 10, 20, and 30week (n ⫽ 8 each), and age-matched male Golden hamsters (Golden) (n ⫽ 8 each) as the control. We performed histological examination (HE, MT, Evans blue, and TUNEL), immunohistochemistry for cathepsin D, electron microscopy (EM), and EM-TUNEL. Compared with Golden, UM-X showed more frequent Evans blue-positive cardiomyocytes with increased permeability of the plasma membrane (Golden, 0 ⫾ 0% vs. UM-X, 0.62 ⫾ 0.48%, p ⬍ 0.05). Similarly, the number of cathepsin D-positive cardiomyocytes in UM-X was greater than that in Golden (Golden, 0.7 ⫾ 0.52% vs. UM-X, 9.6 ⫾ 6.8%, p ⬍ 0.05). Most of the Evans blue-positive cardiomyocytes in UM-X were also positive for cathepsin D. Most importantly, cardiomyocytes were found in hearts of UM-X under electron microscopy, that showed autophagic degeneration with various grades; the autophagic vacuoles contained degraded mitochondria and myelin-like figures. Although the number of TUNEL positive cells in UM-X was greater than that in Golden, those cells were not apoptotic according to electron microscopic TUNEL assay.Degeneration and cell death of UM-X cardiomyocytes are caused by not apotosis, but autophagy.