- Email: [email protected]
Tu-P10:432 Association of C-reactive protein and fibrinogen with the severity of angiographically verified coronary artery disease
Tues&ty, June 20, 2006: Poster Session PIO Biomarkers for cardiovascular disectse I
AN ETHANOL EXTRAT FROM HERB, ITu-P10:429 I BCT-1, I N H I B I T S I N F L A M M A T I O N IN I
LIPOPOLYSACCHARIDE-STIMULATED M A C R O P H A G E S BY S U P P R E S S I N G R E D O X - B A S E D NF-KB A C T I V A T I O N
S.E. Yoo I , K.M. Kim I , M.Y. Park I , J.Y. Choi I , H.M. Shin 2 , J.E. Park I .
1Samsung Medical Center & Samsung Biomedical Research Institute, Sungkyunkwan Universi~ School of Medicine, Seoul, South Korea: 2Departnwnt of Physiology, Dongguk Universi~ College of Oriental Medicbw, Kyongju, South Korea B a c k g r o u n d Objective: BCT-1 is a herbal extract which has antihypertensive effects on spontaneous hypertensive rat and calcium desensitizing effects on aortic strip contraction. We aimed to study whether BCT-1 extracts show anti-inflammatory and anti-oxidant effects in murine macrophage cell lines (RAW 264.7 cells). Methods: We measured the secretion of IL-1V,, TNF-a, nitric oxide (NO) and prostaglandin E2 (PGE2) by ELISA in RAW264.7 cells before and after the stimulation with lipopolysacchaxide(LPS) and with and without coincubation with BCT-1. Western blotting and reverse transcription polymerase chain reaction was also done. Results: BCT-1 significantly inhibited these inflammatory mediators dose dependently by suppressing gene expression of IL-1V,, TNF-a, inducible nitric oxide synthase(iNOS), and cyclooxygenase-2(COX-2). BCT-1 suppressed nuclear transcription factor NF-kB activation in LPS-stimulated RAW264.7 cells, which correlated with its inhibitory effects on lkB-a phosphorylation and degradation. BCT-1 directly blocked the intracellular accumulation of reactive oxygen species (ROS) in RAW264.7 cells stimulated with LPS. Conclusion: BCT-1 possesses anti-inflammatory activities by inhibiting redox-based NF- kB activation, probably through its antioxidant activity. Funding: This work was supported by a grant of the Korea Health 21 R&D Project Ministry of Health & Welfare. Republic of Korea (B050042AM 081505N100020B)
I Tu-P10:430 I C O N C E N T R A T I O N S
OF S E R U M L E P T I N A N D P L A S M A C - R E A C T I V E P R O T E I N IN A D U L T P O P U L A T I O N : E F F E C T OF C O M O R B I D I T I E S
L. Viikari 1 , O. Raltakarl-, J. Vilkan , R. H u u p p o n e n4. 1 Centre of Applied
and Preventive Cardiovascular Medicine, Universi~ of Turku, Turku, Finland; 2Department of Clinical Physiology, Universi~ of Turku, Turku, Finland; 3Department of Medicine, Universi~ of Turku, Turku, Finland," 4Department of Pharmacology and Clinical Pharmacology, Universi~ of Turku, Turku, Finland Objectives: Concentrations of leptin and C-reactive protein (CRP) axe increased in obesity and inflammation, respectively, and their elevation is associated with an increased risk for cardiovascular disease. We analyzed serum leptin and plasma CRP levels in subgroups of subjects with comorbidities and conditions potentially aYfecting them (other than obesity) and compared the concentrations with those seen in apparently healthy subjects. Methods: Serum leptin and plasma CRP were measured in subjects aged 24 to 39 years (1,233 women, 986 men). Subgroups were formed for subjects with rheumatic disease (25W, 9M), recent infection (77W, 36M), diabetes (6W, 7M), high CRP (> 10 mg/L) due to unknown reason (37W, 18M), high triglycerides ( > 4 mmol/L; 3W, 25M), pregnancy (61W) and lactation (53W). The apparently healthy group consisted of 971 women and 891 men. Results: In healthy women median (range) serum leptin and plasma CRP were 12.5 (1.5-63.3) ng/mL and 0.75 (0.05-9.90) mg/L, respectively. In healthy men, the corresponding concentrations were 4.1 (0.8-36.7) ng/mL and 0.56 (0.03-9.65) mg/L. Leptin and CRP were strongly intercorrelated (R=0.47, p<0.0001 for women, R=0.46, p<0.0001 for men). In women both leptin and CRP were significantly higher in the subgroups with rheumatic disease, recent infection, high CRP and pregnancy when compared with healthy women. In men both leptin and CRP were significantly higher in the subgroups with diabetes and high triglycerides. Conclusions: Our results suggest that serum leptin and plasma CRP axe strongly intercorrelated and axe often elevated simultaneously also in non-obese conditions.
279
Tu-P10:4311 E F F E C T OF V E R Y - L O W - C A L O R I E - D I E T ( V L C D ) ON C Y T O K I N E A N D A D H E S I O N M O L E C U L E S IN PATIENTS WITH OBESITY
S. Ust(11, K. Kubold 1 , K. Iso 1 , E. Murakami 3, G. Yoshino 1 . 1Division of Diabetes, Metabolism and Endocrinology, Department of Medicine, Toho Universi~ School of Medicine, Tokyo, Japan." 2Clinical [ztboratotT, Omori Hospital, Toho University School of Medicine, Tokyo, Japan In type 2 diabetic and obese patients, it is reported that the elevation of cytokine and adhesion molecules in serum may play an important role in the progression of vascular disease, including atherosclerosis. However, it has not been clarified whether diet restriction with body weight loss affects serum levels of cytokines and adhesion molecules. We evaluated the effect of verylow-calorie-diet(VLCD) on cytokine and adhension molecules in patients with obesity. Thirteen patients with massive obesity, including diabetic and IGT patients, were enrolled in this study after informed consent was given. Serum levels of IL-18, adiponectin, hs-TNF-alfa, VCAM-1, ICAM-1 and L-selectin were measured in subjects before and after VLCD(600-800kcal/day) for 1-2 weeks(n=13, 13.5-t-l.ldays) and more than 3 weeks(n=8,31.5-t-16.7days). BMI was decreased significantly after treatment with VLCD for 1-2 weeks and more than 3 weeks(33.Smg/m 2 and 31.7mg/m 2, respectively). IL-18 and VCAM-1 increased significantly after treatment for 1-2 weeks, but showed no significant change after treatment for more than 3 weeks. In contrast, serum adiponectin was significantly increased after treatment for more than 3 weeks, but not for 1-2 weeks. No differences were found in the levels of serum hs-TNF-alfa, ICAM-1 and L-selectin during VLCD treatment. We conclude that V L C D treatment within 1-2 weeks, which leads to body weight loss, increased IL-18 and VACM-1 in patients with obesity, suggesting that rapid body weight loss by VLCD within 1-2 weeks may have adverse effects for the prevention of development of vascular complications, such as atherosclerosis. I
T u - P 1 0 : 4 3 2 Ii A S S O C I A T I O N OF C - R E A C T I V E P R O T E I N A N D F I B R I N O G E N W I T H T H E S E V E R I T Y OF ANGIOGRAPHICALLY VERIFIED CORONARY ARTERY DISEASE V. Spasojevic-Kalimanovska, L. Memon, N. Bogavac-Stanojevic, D. Ostric-Kalimanovska, Z. Jelic-Ivanovic, S. Spasic. btstitute of Medical
Biochemistry, Facul~ of Pharntacy, Belgrcule, Serbia - Montenegro Objective: Prospective studies have demonstrated that markers of inflammation, such as high sensitivity C-reactive protein (hsCRP) and fibrinogen, predict future cardiovascular disease risk. However, the association between the hsCRP and fibrinogen levels and the severity of coronary stenosis in patients with coronary artery disease (CAD) remains controversial. The aim of our study was to assess the association of inflammatory markers with the occurrence and severity of CAD. Methods: hsCRP and fibrinogen levels were measured in 188 patients with angiographically assessed CAD. According to the number of significantly stenosed ( > 5 0 % of luminal diameter) vessels, all patients were classified in four groups: without stenosis (0-vessel disease), 1,2 and 3-vessel disease. Serum hsCRP was measured by an immunoturbidimetry assay. Fibrinogen was measured in citrate plasma by Clauss method. Results: The concentrations of hsCRP significantly increased with the severity of CAD defined by the number of stenosed vessels (Kruskal-Wallis test, P<0.05). Plasma fibrinogen concentration also increased with the number of stenosed vessels but the difference was not statistically significant (P=0.34). Ordinal regression analysis indicated hsCRP as an independent predictor for angiographic severity of CAD (beta=0.919, P < 0.001). C o n d u s i o n s : hsCRP and fibrinogen levels were highly elevated in patients with CAD but only the level of hsCRP was an independent predictor of the CAD severity. Funding: The present work was financially supported by the Ministry of Science and Environmental of Protection, Republic of Serbia.
Tu-P10:4331 C - R E A C T I V E P R O T E I N D U R I N G C H R O N I C HEMODIALYSIS TREATMENT
V. Soska, D. Sobotova. St. Ann's Universi~ Hospital, BtT~o, Czech Republic Objective: C-reactive protein (CRP) is a marker of both inflammation and risk of atherosclerosis. It in known that CRP level is elevated in hemodialysed patients. The aim of this study was to examine if serum CRP level depends on the duration of chronic hemodialysis programme.
XIV bztetTtational Symposium on Atherosclerosis, Rome, Italy, June 18-22, 2006
AN ETHANOL EXTRAT FROM HERB, ITu-P10:429 I BCT-1, I N H I B I T S I N F L A M M A T I O N IN I
LIPOPOLYSACCHARIDE-STIMULATED M A C R O P H A G E S BY S U P P R E S S I N G R E D O X - B A S E D NF-KB A C T I V A T I O N
S.E. Yoo I , K.M. Kim I , M.Y. Park I , J.Y. Choi I , H.M. Shin 2 , J.E. Park I .
1Samsung Medical Center & Samsung Biomedical Research Institute, Sungkyunkwan Universi~ School of Medicine, Seoul, South Korea: 2Departnwnt of Physiology, Dongguk Universi~ College of Oriental Medicbw, Kyongju, South Korea B a c k g r o u n d Objective: BCT-1 is a herbal extract which has antihypertensive effects on spontaneous hypertensive rat and calcium desensitizing effects on aortic strip contraction. We aimed to study whether BCT-1 extracts show anti-inflammatory and anti-oxidant effects in murine macrophage cell lines (RAW 264.7 cells). Methods: We measured the secretion of IL-1V,, TNF-a, nitric oxide (NO) and prostaglandin E2 (PGE2) by ELISA in RAW264.7 cells before and after the stimulation with lipopolysacchaxide(LPS) and with and without coincubation with BCT-1. Western blotting and reverse transcription polymerase chain reaction was also done. Results: BCT-1 significantly inhibited these inflammatory mediators dose dependently by suppressing gene expression of IL-1V,, TNF-a, inducible nitric oxide synthase(iNOS), and cyclooxygenase-2(COX-2). BCT-1 suppressed nuclear transcription factor NF-kB activation in LPS-stimulated RAW264.7 cells, which correlated with its inhibitory effects on lkB-a phosphorylation and degradation. BCT-1 directly blocked the intracellular accumulation of reactive oxygen species (ROS) in RAW264.7 cells stimulated with LPS. Conclusion: BCT-1 possesses anti-inflammatory activities by inhibiting redox-based NF- kB activation, probably through its antioxidant activity. Funding: This work was supported by a grant of the Korea Health 21 R&D Project Ministry of Health & Welfare. Republic of Korea (B050042AM 081505N100020B)
I Tu-P10:430 I C O N C E N T R A T I O N S
OF S E R U M L E P T I N A N D P L A S M A C - R E A C T I V E P R O T E I N IN A D U L T P O P U L A T I O N : E F F E C T OF C O M O R B I D I T I E S
L. Viikari 1 , O. Raltakarl-, J. Vilkan , R. H u u p p o n e n4. 1 Centre of Applied
and Preventive Cardiovascular Medicine, Universi~ of Turku, Turku, Finland; 2Department of Clinical Physiology, Universi~ of Turku, Turku, Finland; 3Department of Medicine, Universi~ of Turku, Turku, Finland," 4Department of Pharmacology and Clinical Pharmacology, Universi~ of Turku, Turku, Finland Objectives: Concentrations of leptin and C-reactive protein (CRP) axe increased in obesity and inflammation, respectively, and their elevation is associated with an increased risk for cardiovascular disease. We analyzed serum leptin and plasma CRP levels in subgroups of subjects with comorbidities and conditions potentially aYfecting them (other than obesity) and compared the concentrations with those seen in apparently healthy subjects. Methods: Serum leptin and plasma CRP were measured in subjects aged 24 to 39 years (1,233 women, 986 men). Subgroups were formed for subjects with rheumatic disease (25W, 9M), recent infection (77W, 36M), diabetes (6W, 7M), high CRP (> 10 mg/L) due to unknown reason (37W, 18M), high triglycerides ( > 4 mmol/L; 3W, 25M), pregnancy (61W) and lactation (53W). The apparently healthy group consisted of 971 women and 891 men. Results: In healthy women median (range) serum leptin and plasma CRP were 12.5 (1.5-63.3) ng/mL and 0.75 (0.05-9.90) mg/L, respectively. In healthy men, the corresponding concentrations were 4.1 (0.8-36.7) ng/mL and 0.56 (0.03-9.65) mg/L. Leptin and CRP were strongly intercorrelated (R=0.47, p<0.0001 for women, R=0.46, p<0.0001 for men). In women both leptin and CRP were significantly higher in the subgroups with rheumatic disease, recent infection, high CRP and pregnancy when compared with healthy women. In men both leptin and CRP were significantly higher in the subgroups with diabetes and high triglycerides. Conclusions: Our results suggest that serum leptin and plasma CRP axe strongly intercorrelated and axe often elevated simultaneously also in non-obese conditions.
279
Tu-P10:4311 E F F E C T OF V E R Y - L O W - C A L O R I E - D I E T ( V L C D ) ON C Y T O K I N E A N D A D H E S I O N M O L E C U L E S IN PATIENTS WITH OBESITY
S. Ust(11, K. Kubold 1 , K. Iso 1 , E. Murakami 3, G. Yoshino 1 . 1Division of Diabetes, Metabolism and Endocrinology, Department of Medicine, Toho Universi~ School of Medicine, Tokyo, Japan." 2Clinical [ztboratotT, Omori Hospital, Toho University School of Medicine, Tokyo, Japan In type 2 diabetic and obese patients, it is reported that the elevation of cytokine and adhesion molecules in serum may play an important role in the progression of vascular disease, including atherosclerosis. However, it has not been clarified whether diet restriction with body weight loss affects serum levels of cytokines and adhesion molecules. We evaluated the effect of verylow-calorie-diet(VLCD) on cytokine and adhension molecules in patients with obesity. Thirteen patients with massive obesity, including diabetic and IGT patients, were enrolled in this study after informed consent was given. Serum levels of IL-18, adiponectin, hs-TNF-alfa, VCAM-1, ICAM-1 and L-selectin were measured in subjects before and after VLCD(600-800kcal/day) for 1-2 weeks(n=13, 13.5-t-l.ldays) and more than 3 weeks(n=8,31.5-t-16.7days). BMI was decreased significantly after treatment with VLCD for 1-2 weeks and more than 3 weeks(33.Smg/m 2 and 31.7mg/m 2, respectively). IL-18 and VCAM-1 increased significantly after treatment for 1-2 weeks, but showed no significant change after treatment for more than 3 weeks. In contrast, serum adiponectin was significantly increased after treatment for more than 3 weeks, but not for 1-2 weeks. No differences were found in the levels of serum hs-TNF-alfa, ICAM-1 and L-selectin during VLCD treatment. We conclude that V L C D treatment within 1-2 weeks, which leads to body weight loss, increased IL-18 and VACM-1 in patients with obesity, suggesting that rapid body weight loss by VLCD within 1-2 weeks may have adverse effects for the prevention of development of vascular complications, such as atherosclerosis. I
T u - P 1 0 : 4 3 2 Ii A S S O C I A T I O N OF C - R E A C T I V E P R O T E I N A N D F I B R I N O G E N W I T H T H E S E V E R I T Y OF ANGIOGRAPHICALLY VERIFIED CORONARY ARTERY DISEASE V. Spasojevic-Kalimanovska, L. Memon, N. Bogavac-Stanojevic, D. Ostric-Kalimanovska, Z. Jelic-Ivanovic, S. Spasic. btstitute of Medical
Biochemistry, Facul~ of Pharntacy, Belgrcule, Serbia - Montenegro Objective: Prospective studies have demonstrated that markers of inflammation, such as high sensitivity C-reactive protein (hsCRP) and fibrinogen, predict future cardiovascular disease risk. However, the association between the hsCRP and fibrinogen levels and the severity of coronary stenosis in patients with coronary artery disease (CAD) remains controversial. The aim of our study was to assess the association of inflammatory markers with the occurrence and severity of CAD. Methods: hsCRP and fibrinogen levels were measured in 188 patients with angiographically assessed CAD. According to the number of significantly stenosed ( > 5 0 % of luminal diameter) vessels, all patients were classified in four groups: without stenosis (0-vessel disease), 1,2 and 3-vessel disease. Serum hsCRP was measured by an immunoturbidimetry assay. Fibrinogen was measured in citrate plasma by Clauss method. Results: The concentrations of hsCRP significantly increased with the severity of CAD defined by the number of stenosed vessels (Kruskal-Wallis test, P<0.05). Plasma fibrinogen concentration also increased with the number of stenosed vessels but the difference was not statistically significant (P=0.34). Ordinal regression analysis indicated hsCRP as an independent predictor for angiographic severity of CAD (beta=0.919, P < 0.001). C o n d u s i o n s : hsCRP and fibrinogen levels were highly elevated in patients with CAD but only the level of hsCRP was an independent predictor of the CAD severity. Funding: The present work was financially supported by the Ministry of Science and Environmental of Protection, Republic of Serbia.
Tu-P10:4331 C - R E A C T I V E P R O T E I N D U R I N G C H R O N I C HEMODIALYSIS TREATMENT
V. Soska, D. Sobotova. St. Ann's Universi~ Hospital, BtT~o, Czech Republic Objective: C-reactive protein (CRP) is a marker of both inflammation and risk of atherosclerosis. It in known that CRP level is elevated in hemodialysed patients. The aim of this study was to examine if serum CRP level depends on the duration of chronic hemodialysis programme.
XIV bztetTtational Symposium on Atherosclerosis, Rome, Italy, June 18-22, 2006