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Serum Matrix Metalloproteinases Profile in Patients with Heart Failure
The 9th Annual Scientific Meeting
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JHFS
S287
O-049
O-051
Serum Matrix Metalloproteinases Profile in Patients with Heart Failure
Serum Level of Uric Acid, Partly Secreted From The Failing Heart, is a Prognostic Marker in Patients with CHF HIROSHI SAKAI, TAKAYOSHI TSUTAMOTO, CHITOSE ISHIKAWA, TOSHINARI TANAKA, MINORU HORIE Department of Cardiovascular and Respiratory Medicine,Shiga University of medical science, Japan
HIROYASU UZUI, AKIRA NAKANO, NAOKI AMAYA, HARUHISA SIRASAKI, TOSHIHIRO MIZUGUCHI, JUNJI SAKATA, MICHITOMO KAWAHITO, TAKANORI UEDA, JONG-DAE LEE First Department of Internal Medicine, Faculty of Medical Sciences,University of Fukui, Fukui, Japan Background: Although several matrix metalloproteinases (MMPs) activation in congestive heart failure (CHF) are reported, it remains unclear whether activation of MMPs species is evident in CHF. The objective is to estimate the profile of MMPs in CHF. Methods: Serum levels of MMPs were measured in patients with CHF (ischemic (ICM), idiopathic dilated cardiomyopathy (DCM)) and compared with control subjects. Response to beta-blocker therapy was assessed at 6 months comparing with baseline data. Results: (Table).The responders/non-responders ratio to beta-blocker therapy in patients with high levels of MMP-9 (over 70 ng/ml) was significantly lower than patients with MMP-9 level of 70 ng/ml or less (p⫽0.0078). Conclusion: The serum MMP-9 level is differed by the etiologies of the congestive heart failure, and it is useful to assess the level for the selection of the treatment strategy.
Background: Activation of xanthine oxidase is a mechanism for elevation of serum UA in CHF. However, whether UA is secreted from the failing heart remains unknown. Objective: To evaluate serum UA is secreted from the failing heart and to estimate the prognostic role of UA in Japanese patients with CHF. Methods: We measured the serum UA in the Aortic root (AO) and in the coronary sinus (CS) in 58 patients with CHF and 13 control subjects. In 150 CHF patients, we measured plasma levels of norepinephrine, BNP, UA, and LVEF and monitored for more than one year prospectively. Results: In 58 CHF patients, serum UA level was significantly higher in the CS than the AO. The transcardiac gradient of UA (CS-AO) increased with severity of CHF and inversely correlated with LVEF and positively correlated with LV end-diastolic volume index. During the long-term follow-up, 26 patients died of cardiac event. In 150 CHF patients, high plasma levels of UA and BNP were shown to be independent predictors of mortality by multivariate stepwise analysis. 20 patients died in 49 patients (BNP⬎130 pg/mL and UA⬎6mg/dL). Conclusions: These findings suggest that activated XO system in the failing heart contributes to the left ventricular dysfunction and the high plasma UA level is an independent prognostic predictor of BNP in Japanese patients with CHF.
O-050
O-052
Vascular Extracellular Superoxide Dismutase and Urinary 8-isoprostane Increase in Patients with Acute Phase-Congestive Heart Failure TAKAHIRO KUBARA, KAZUHITO YAMASHITA, SEIYA TANAKA, RYOUJI KOUZUMA, MASAHIRO OKAZAKI, HIROMI TASAKI, YASUHIDE NAKASHIMA Second Department of Internal Medicine, University Occupational Environmental Health, Kitakyushu, Japan
Transient Reduction of Peripheral Blood Dendritic Cells in Patients with Acute Decompensated Heart Failure YUSUKE SUGI1, HIDEO YASUKAWA2, HISASHI KAI1, TSUTOMU IMAIZUMI1 1 Department of Internal Medicine(III), Kurume University, Kurume, Japan, 2 Cardiovascular Research Institute, Kurume University, Kurume, Japan
Background: In congestive heart failure (CHF), an imbalance of reactive oxygen species and its defensive mechanisms is not fully understood. This study was undertaken to elucidate whether EC-SOD levels, a major antioxidative enzyme, and urinary 8-isoprostane, an oxygen stress marker, would be changed in patients with CHF. Methods: Twenty patients (9 male, 69.6⫾12.1y.o.) with CHF were studied EC-SOD, urinary 8-isoprostane and other parameters at acute and recovered stages. Age-sex-matched subjects were also employed as control. Results: Basal and endothelium-bound levels of EC-SOD were significantly elevated at acute stage (114.3⫾54.8 and 187.0⫾95.8 ng/ml) compared to those at recovered stage (92.9⫾44.7 and 119.0⫾45.4 ng/ml, p⫽0.019, p⫽0.007, respectively). Similarly, urinary 8-isoprostane was also increased at acute phase (134.8⫾83.5 pg/mg cr.) and was significantly decreased to 88.4⫾60.6 pg/mg cr.(p⫽0.0007). The values of EC-SOD were well correlated with the plasma level of BNP or ANP, NYHA classification and heart rate, but not with 8-isoprostane. Endothelium-bound EC-SOD at acute phase was also correlated with plasma angiotensin II (r⫽0.551, p⫽0.012). By contrast, the levels of EC-SOD were not changed in control group after similar intervals. Conclusion: This study suggests that the significant increase of vascular EC-SOD and 8-isoprostane are recognized in CHF. Oxygen stress might play a crucial role in severe CHF patients.
Although increasing evidence supports a role for immune-mediated inflammation in the development and progression of chronic heart failure (CHF), little is known regarding the source and the mechanism for this immune activation. Dendritic cells (DC) are the most potent antigenpresenting cells that play a central role in initiating the primary immune response. DC comprise two distinct functional subsets, myeloid DC (mDC) and plasmacytoid DC (pDC). We hypothesized that circulating DC numbers could be altered during an episode of decompensation in patients with CHF. Methods: We examined the numbers of mDC and pDC in the peripheral blood of acute decompensated CHF patients (n⫽13) and age-matched normal subjects (n⫽14), using multi color flow cytometry. The circulating DC numbers were also measured in clinically compensated state. Results: We found that the numbers of total DC, mDC and pDC were markedly reduced in acute decompensated CHF patients compared with normal subjects (p⬍0.001). Surprisingly, mDC in two CHF and pDC in three CHF patients were virtually absent. The circulating mDC numbers were significantly increased after standard CHF treatment (p⬍0.05), associated with a significant decrease of B-type natriuretic peptide (p⬍0.05). There was no significant difference in the total numbers of white blood cells two groups. Conclusion: These data suggest that DC may play important roles in the decompensation of CHF.
•
JHFS
S287
O-049
O-051
Serum Matrix Metalloproteinases Profile in Patients with Heart Failure
Serum Level of Uric Acid, Partly Secreted From The Failing Heart, is a Prognostic Marker in Patients with CHF HIROSHI SAKAI, TAKAYOSHI TSUTAMOTO, CHITOSE ISHIKAWA, TOSHINARI TANAKA, MINORU HORIE Department of Cardiovascular and Respiratory Medicine,Shiga University of medical science, Japan
HIROYASU UZUI, AKIRA NAKANO, NAOKI AMAYA, HARUHISA SIRASAKI, TOSHIHIRO MIZUGUCHI, JUNJI SAKATA, MICHITOMO KAWAHITO, TAKANORI UEDA, JONG-DAE LEE First Department of Internal Medicine, Faculty of Medical Sciences,University of Fukui, Fukui, Japan Background: Although several matrix metalloproteinases (MMPs) activation in congestive heart failure (CHF) are reported, it remains unclear whether activation of MMPs species is evident in CHF. The objective is to estimate the profile of MMPs in CHF. Methods: Serum levels of MMPs were measured in patients with CHF (ischemic (ICM), idiopathic dilated cardiomyopathy (DCM)) and compared with control subjects. Response to beta-blocker therapy was assessed at 6 months comparing with baseline data. Results: (Table).The responders/non-responders ratio to beta-blocker therapy in patients with high levels of MMP-9 (over 70 ng/ml) was significantly lower than patients with MMP-9 level of 70 ng/ml or less (p⫽0.0078). Conclusion: The serum MMP-9 level is differed by the etiologies of the congestive heart failure, and it is useful to assess the level for the selection of the treatment strategy.
Background: Activation of xanthine oxidase is a mechanism for elevation of serum UA in CHF. However, whether UA is secreted from the failing heart remains unknown. Objective: To evaluate serum UA is secreted from the failing heart and to estimate the prognostic role of UA in Japanese patients with CHF. Methods: We measured the serum UA in the Aortic root (AO) and in the coronary sinus (CS) in 58 patients with CHF and 13 control subjects. In 150 CHF patients, we measured plasma levels of norepinephrine, BNP, UA, and LVEF and monitored for more than one year prospectively. Results: In 58 CHF patients, serum UA level was significantly higher in the CS than the AO. The transcardiac gradient of UA (CS-AO) increased with severity of CHF and inversely correlated with LVEF and positively correlated with LV end-diastolic volume index. During the long-term follow-up, 26 patients died of cardiac event. In 150 CHF patients, high plasma levels of UA and BNP were shown to be independent predictors of mortality by multivariate stepwise analysis. 20 patients died in 49 patients (BNP⬎130 pg/mL and UA⬎6mg/dL). Conclusions: These findings suggest that activated XO system in the failing heart contributes to the left ventricular dysfunction and the high plasma UA level is an independent prognostic predictor of BNP in Japanese patients with CHF.
O-050
O-052
Vascular Extracellular Superoxide Dismutase and Urinary 8-isoprostane Increase in Patients with Acute Phase-Congestive Heart Failure TAKAHIRO KUBARA, KAZUHITO YAMASHITA, SEIYA TANAKA, RYOUJI KOUZUMA, MASAHIRO OKAZAKI, HIROMI TASAKI, YASUHIDE NAKASHIMA Second Department of Internal Medicine, University Occupational Environmental Health, Kitakyushu, Japan
Transient Reduction of Peripheral Blood Dendritic Cells in Patients with Acute Decompensated Heart Failure YUSUKE SUGI1, HIDEO YASUKAWA2, HISASHI KAI1, TSUTOMU IMAIZUMI1 1 Department of Internal Medicine(III), Kurume University, Kurume, Japan, 2 Cardiovascular Research Institute, Kurume University, Kurume, Japan
Background: In congestive heart failure (CHF), an imbalance of reactive oxygen species and its defensive mechanisms is not fully understood. This study was undertaken to elucidate whether EC-SOD levels, a major antioxidative enzyme, and urinary 8-isoprostane, an oxygen stress marker, would be changed in patients with CHF. Methods: Twenty patients (9 male, 69.6⫾12.1y.o.) with CHF were studied EC-SOD, urinary 8-isoprostane and other parameters at acute and recovered stages. Age-sex-matched subjects were also employed as control. Results: Basal and endothelium-bound levels of EC-SOD were significantly elevated at acute stage (114.3⫾54.8 and 187.0⫾95.8 ng/ml) compared to those at recovered stage (92.9⫾44.7 and 119.0⫾45.4 ng/ml, p⫽0.019, p⫽0.007, respectively). Similarly, urinary 8-isoprostane was also increased at acute phase (134.8⫾83.5 pg/mg cr.) and was significantly decreased to 88.4⫾60.6 pg/mg cr.(p⫽0.0007). The values of EC-SOD were well correlated with the plasma level of BNP or ANP, NYHA classification and heart rate, but not with 8-isoprostane. Endothelium-bound EC-SOD at acute phase was also correlated with plasma angiotensin II (r⫽0.551, p⫽0.012). By contrast, the levels of EC-SOD were not changed in control group after similar intervals. Conclusion: This study suggests that the significant increase of vascular EC-SOD and 8-isoprostane are recognized in CHF. Oxygen stress might play a crucial role in severe CHF patients.
Although increasing evidence supports a role for immune-mediated inflammation in the development and progression of chronic heart failure (CHF), little is known regarding the source and the mechanism for this immune activation. Dendritic cells (DC) are the most potent antigenpresenting cells that play a central role in initiating the primary immune response. DC comprise two distinct functional subsets, myeloid DC (mDC) and plasmacytoid DC (pDC). We hypothesized that circulating DC numbers could be altered during an episode of decompensation in patients with CHF. Methods: We examined the numbers of mDC and pDC in the peripheral blood of acute decompensated CHF patients (n⫽13) and age-matched normal subjects (n⫽14), using multi color flow cytometry. The circulating DC numbers were also measured in clinically compensated state. Results: We found that the numbers of total DC, mDC and pDC were markedly reduced in acute decompensated CHF patients compared with normal subjects (p⬍0.001). Surprisingly, mDC in two CHF and pDC in three CHF patients were virtually absent. The circulating mDC numbers were significantly increased after standard CHF treatment (p⬍0.05), associated with a significant decrease of B-type natriuretic peptide (p⬍0.05). There was no significant difference in the total numbers of white blood cells two groups. Conclusion: These data suggest that DC may play important roles in the decompensation of CHF.