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Upregulation of inflammatory mediators, cyclooxygenase-2, lipoxygenase and AT-1 receptor in the metabolic syndrome
AJH–May 2005–VOL. 18, NO. 5, PART 2
measures included: blood pressure (by sphygmomanometer); fasting triglycerides, HDL cholesterol; glucose (enzymatic); and waist circumference (tape measure). By ATP-III criteria, the prevalence of MS was 15.6% (16.3% in men; 15.1% in women). Presence of MS had low sensitivity to detect IR (45% in men; 39% in women) but high specificity (93% in men; 95% in women). Diagnostic accuracy was fair based on the area under the ROC curve (AUC) constructed by counting MS components as recommended by ATP-III (AUC⫽ 0.797 in men; 0.747 in women). When component MS measures were considered as quantitative traits, blood pressure levels had the lowest diagnostic accuracy for IR (AUC⫽ 0.627 in men; 0.572 in women) and waist circumference had the highest (AUC⫽ 0.906 in men; 822 in women). Cutpoint values of waist circumference that optimized diagnostic accuracy for IR differed from those recommended by ATP-III (92 cm in men [vs 102 cm]; 82 cm in women [vs 88 cm]). In screening asymptomatic white adults, application of the ATP-III MS criteria provides good specificity but low sensitivity in diagnosing IR. Measuring just waist circumference is simpler and provides greater diagnostic accuracy for IR. Key Words: Diagnostic Accuracy, Insulin Resistance, Metabolic Syndrome
P-545 CARDIO-VASCULAR INSUFFICIENCY AND PHOSPHOLIPIDE SYNDROME IN PATIENTS WITH DIABETES TYPE II Larysa P Sydorchuk, Igor I Sydorchuk, Ruslan I Sydorchuk. Cardiology Dpt, Bucovinian State Medical Academy, Chernivtsi, Ukraine. Background: There is no clear concept concerning the role of immune disorders in pathogenesis of cardio-vascular insufficiency (CVI). The aim of the study was to evaluate the levels of antiphospholipid antibodies dependently of CVI stages and complications appearance in patients with verified non-inflammatory thrombotic vessels pathology (NITVP) and metabolic disorders - diabetes type II. Methods: One hundred fifty four patients with NITVP and diabetes type II were involved into the study (64 men and 90 women, mean age 58.4⫾4.1 years): 1st group included 25 patients with CVI II; 2nd group – 20 patients with CVI III, complicated with cerebral ischemic insults and acute myocardial infarctions; control group included 10 patients with CVI I. All patients were tested for presence of NITVP and CVI by Doppler ultrasonography, duplex scanning, angiography, Echo-CG, Reoencephalography, BP and ECG holter-monitoring, clinical laboratory examination. For research purpose the antibodies to cardiolipine (AKL) isotypes IgG and IgM were typified with the standard immune-enzyme method (ELISA), titres of antibodies to myocardial, renal, cerebral and vascular intimae antigens were investigated. Results: Isotype of IgMG-AKL antibodies’ increasing was revealed in 5 patients of 1st group. Isotypes of IgG-AKL and IgM-AKL antibodies increased in 5 and 4 patients of the 2nd group, accordingly. The titres of antibodies to myocardial, renal, cerebral and vascular intimae antigens were significantly higher in the patients of 1st and 2nd groups comparatively to the control group (p⬍0.05). Level of antibodies to target-organs antigens most closely correlated to the CVI in 2nd group (the highest correlation indices). Smaller, but still strong correlation coefficients of CVI to myocardial, renal, cerebral and vascular intimae antigens antibodies were in 1st group. Conclusion: The antiphospholipid antibodies were revealed in 31% of the patients with NITVP. Both level of IgG-AKL and IgM-AKL or antiintimae, antirenal, antimyocardial and anticerebral antibodies was respective to CVI stage showing dependences between vascular failure, complications appearance and immune disorders in patients with diabetes type II. Key Words: AntiphospholipidSyndrome, Cardio-Vessels Insufficiency, Thrombotic Vessels Pathology
POSTERS: Metabolic Syndrome
205A
P-546 UPREGULATION OF INFLAMMATORY MEDIATORS, CYCLOOXYGENASE-2, LIPOXYGENASE AND AT-1 RECEPTOR IN THE METABOLIC SYNDROME N. D. Vaziri, G. Xu, L. Lanting, Z. Li, L. Sepassi, B. Rodriguez-Inturbe, R. Natarajan. Division of Nephrology and Hypertension, University of California, Irvine, Irvine, CA; Diabetes Dept., City of Hope, Duarte, CA; Nephrologia, Hospital Universitario, Maracaibo, Venezuela. Background: Metabolic syndrome has emerged as the major cause of atherosclerosis and chronic kidney disease. These events are associated with and, in part, due to oxidative stress and inflammation. Life style modifications, weight reduction and blockade of renin-angiotensin system have been shown to retard progression of the renal and cardiovascular complications in metabolic syndrome. In an attempt to explore the molecular sources of inflammation and possible involvement of reninangiotensin system in metabolic syndrome, we studied obese Zucker rats which exhibit obesity, insulin resistance, hyperlipidemia and progressive glomerulosclerosis. Methods and Results: Seven-week-old male obese Zucker rats were randomized to losartan treated (100 mg/L drinking H2O) and untreated groups. Lean Zucker rats served as controls. After 4 months, aortas and renal cortex were obtained and processed for RT-PCR, Western blot and immunohistochemical analyses. Compared to the lean controls, obese Zucker rats showed significant glomerular matrix (ECM) expansion, increased mRNA and protein expressions of fibronectin, interleukin-6, monocyte chemoattractant protein-1, and two major enzymes of arachidonate metabolism, namely 12/15-lipoxygenase and cyclooxygenase-2. This was associated with significant increases in p38 and ERK1/2 MAP kinase activities, as well as, marked upregulation of angiotensin II type 1 receptor (AT1R) mRNA and protein expressions. These abnormalities, as well as, the associated glomerulopathy and proteinuria were prevented by administration of the AT1R blocker (ARB), losartan. Similarly, p38 and ERK1/2 MAP kinase activities were elevated in the aortas of obese Zucker rats and were lowered by ARB administration. Conclusions: The metabolic syndrome is associated with up-regulation of the key inflammatory mediators in the kidney and the conduit arteries. These events are associated with and perhaps, in part, due to upregulation of AT1R as evidenced by their reversal with ARB treatment. Key Words: Kidney Disease, Metabolic Syndrome, Obesity
P-547 TARGET ORGAN DAMAGE AND METABOLIC SYNDROME IN NON DIABETIC HYPERTENSIVE PATIENTS Francesca Viazzi, Giovanna Leoncini, Elena Ratto, Valentina Vaccaro, Valeria Falqui, Angelica Parodi, Cinzia Tomolillo, Giacomo Deferrari, Roberto Pontremoli. Department of Internal Medicine, University of Genoa, Genoa, Genoa, Italy. Metabolic syndrome increases the risk of cardiovascular disease in hypertensive patients. To get a better understanding of the pathophysiologic mechanisms underlying this association we analyzed the relationship between metabolic syndrome and target organ damage in a large group of hypertensive patients. Three hundred and fifty-four never treated, non diabetic patients with essential hypertension were included in the study. A modified ATP-III definition for metabolic syndrome was used, with body mass index replacing waist circumference. Albuminuria was measured as albumin to creatinine ratio in three non consecutive first morning urine samples. Left ventricular mass index was assessed by echocardiography, carotid abnormalities were evaluated by ultrasonographic scan. The prevalence of metabolic syndrome was 21%. Patients with metabolic syndrome showed higher prevalence of microalbuminuria (P⫽0.03)
measures included: blood pressure (by sphygmomanometer); fasting triglycerides, HDL cholesterol; glucose (enzymatic); and waist circumference (tape measure). By ATP-III criteria, the prevalence of MS was 15.6% (16.3% in men; 15.1% in women). Presence of MS had low sensitivity to detect IR (45% in men; 39% in women) but high specificity (93% in men; 95% in women). Diagnostic accuracy was fair based on the area under the ROC curve (AUC) constructed by counting MS components as recommended by ATP-III (AUC⫽ 0.797 in men; 0.747 in women). When component MS measures were considered as quantitative traits, blood pressure levels had the lowest diagnostic accuracy for IR (AUC⫽ 0.627 in men; 0.572 in women) and waist circumference had the highest (AUC⫽ 0.906 in men; 822 in women). Cutpoint values of waist circumference that optimized diagnostic accuracy for IR differed from those recommended by ATP-III (92 cm in men [vs 102 cm]; 82 cm in women [vs 88 cm]). In screening asymptomatic white adults, application of the ATP-III MS criteria provides good specificity but low sensitivity in diagnosing IR. Measuring just waist circumference is simpler and provides greater diagnostic accuracy for IR. Key Words: Diagnostic Accuracy, Insulin Resistance, Metabolic Syndrome
P-545 CARDIO-VASCULAR INSUFFICIENCY AND PHOSPHOLIPIDE SYNDROME IN PATIENTS WITH DIABETES TYPE II Larysa P Sydorchuk, Igor I Sydorchuk, Ruslan I Sydorchuk. Cardiology Dpt, Bucovinian State Medical Academy, Chernivtsi, Ukraine. Background: There is no clear concept concerning the role of immune disorders in pathogenesis of cardio-vascular insufficiency (CVI). The aim of the study was to evaluate the levels of antiphospholipid antibodies dependently of CVI stages and complications appearance in patients with verified non-inflammatory thrombotic vessels pathology (NITVP) and metabolic disorders - diabetes type II. Methods: One hundred fifty four patients with NITVP and diabetes type II were involved into the study (64 men and 90 women, mean age 58.4⫾4.1 years): 1st group included 25 patients with CVI II; 2nd group – 20 patients with CVI III, complicated with cerebral ischemic insults and acute myocardial infarctions; control group included 10 patients with CVI I. All patients were tested for presence of NITVP and CVI by Doppler ultrasonography, duplex scanning, angiography, Echo-CG, Reoencephalography, BP and ECG holter-monitoring, clinical laboratory examination. For research purpose the antibodies to cardiolipine (AKL) isotypes IgG and IgM were typified with the standard immune-enzyme method (ELISA), titres of antibodies to myocardial, renal, cerebral and vascular intimae antigens were investigated. Results: Isotype of IgMG-AKL antibodies’ increasing was revealed in 5 patients of 1st group. Isotypes of IgG-AKL and IgM-AKL antibodies increased in 5 and 4 patients of the 2nd group, accordingly. The titres of antibodies to myocardial, renal, cerebral and vascular intimae antigens were significantly higher in the patients of 1st and 2nd groups comparatively to the control group (p⬍0.05). Level of antibodies to target-organs antigens most closely correlated to the CVI in 2nd group (the highest correlation indices). Smaller, but still strong correlation coefficients of CVI to myocardial, renal, cerebral and vascular intimae antigens antibodies were in 1st group. Conclusion: The antiphospholipid antibodies were revealed in 31% of the patients with NITVP. Both level of IgG-AKL and IgM-AKL or antiintimae, antirenal, antimyocardial and anticerebral antibodies was respective to CVI stage showing dependences between vascular failure, complications appearance and immune disorders in patients with diabetes type II. Key Words: AntiphospholipidSyndrome, Cardio-Vessels Insufficiency, Thrombotic Vessels Pathology
POSTERS: Metabolic Syndrome
205A
P-546 UPREGULATION OF INFLAMMATORY MEDIATORS, CYCLOOXYGENASE-2, LIPOXYGENASE AND AT-1 RECEPTOR IN THE METABOLIC SYNDROME N. D. Vaziri, G. Xu, L. Lanting, Z. Li, L. Sepassi, B. Rodriguez-Inturbe, R. Natarajan. Division of Nephrology and Hypertension, University of California, Irvine, Irvine, CA; Diabetes Dept., City of Hope, Duarte, CA; Nephrologia, Hospital Universitario, Maracaibo, Venezuela. Background: Metabolic syndrome has emerged as the major cause of atherosclerosis and chronic kidney disease. These events are associated with and, in part, due to oxidative stress and inflammation. Life style modifications, weight reduction and blockade of renin-angiotensin system have been shown to retard progression of the renal and cardiovascular complications in metabolic syndrome. In an attempt to explore the molecular sources of inflammation and possible involvement of reninangiotensin system in metabolic syndrome, we studied obese Zucker rats which exhibit obesity, insulin resistance, hyperlipidemia and progressive glomerulosclerosis. Methods and Results: Seven-week-old male obese Zucker rats were randomized to losartan treated (100 mg/L drinking H2O) and untreated groups. Lean Zucker rats served as controls. After 4 months, aortas and renal cortex were obtained and processed for RT-PCR, Western blot and immunohistochemical analyses. Compared to the lean controls, obese Zucker rats showed significant glomerular matrix (ECM) expansion, increased mRNA and protein expressions of fibronectin, interleukin-6, monocyte chemoattractant protein-1, and two major enzymes of arachidonate metabolism, namely 12/15-lipoxygenase and cyclooxygenase-2. This was associated with significant increases in p38 and ERK1/2 MAP kinase activities, as well as, marked upregulation of angiotensin II type 1 receptor (AT1R) mRNA and protein expressions. These abnormalities, as well as, the associated glomerulopathy and proteinuria were prevented by administration of the AT1R blocker (ARB), losartan. Similarly, p38 and ERK1/2 MAP kinase activities were elevated in the aortas of obese Zucker rats and were lowered by ARB administration. Conclusions: The metabolic syndrome is associated with up-regulation of the key inflammatory mediators in the kidney and the conduit arteries. These events are associated with and perhaps, in part, due to upregulation of AT1R as evidenced by their reversal with ARB treatment. Key Words: Kidney Disease, Metabolic Syndrome, Obesity
P-547 TARGET ORGAN DAMAGE AND METABOLIC SYNDROME IN NON DIABETIC HYPERTENSIVE PATIENTS Francesca Viazzi, Giovanna Leoncini, Elena Ratto, Valentina Vaccaro, Valeria Falqui, Angelica Parodi, Cinzia Tomolillo, Giacomo Deferrari, Roberto Pontremoli. Department of Internal Medicine, University of Genoa, Genoa, Genoa, Italy. Metabolic syndrome increases the risk of cardiovascular disease in hypertensive patients. To get a better understanding of the pathophysiologic mechanisms underlying this association we analyzed the relationship between metabolic syndrome and target organ damage in a large group of hypertensive patients. Three hundred and fifty-four never treated, non diabetic patients with essential hypertension were included in the study. A modified ATP-III definition for metabolic syndrome was used, with body mass index replacing waist circumference. Albuminuria was measured as albumin to creatinine ratio in three non consecutive first morning urine samples. Left ventricular mass index was assessed by echocardiography, carotid abnormalities were evaluated by ultrasonographic scan. The prevalence of metabolic syndrome was 21%. Patients with metabolic syndrome showed higher prevalence of microalbuminuria (P⫽0.03)