Nitric oxide and pro-inflammatory cytokine serum levels in postmenopausal women with the metabolic syndrome

Background: The metabolic syndrome (METS) increases after the menopause which may enhance cardiovascular risk in part explained by a pro-inflammatory state. Objective: Measure nitric oxide (NO), tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6) serum levels in postmenopausal women with and without the METS (Adult Treatment Panel III criteria). Methods: Analyte levels were compared among those with and without the syndrome and each of its diagnostic components. Rho Spearman coefficients were also calculated to determine correlations between analyte levels and various numeric variables. Results: Median age of all studied women (n = 88) was 54.4 years, 62.5% had abdominal obesity, 14.8% hyperglycemia, 59.1% high triglycerides (TG) and 44.3% hypertension. Women with the METS (n = 44) displayed higher body mass index values and higher rates of abdominal obesity, hyperglycemia, hypertriglyceridemia, hypertension and low HDL-C levels. Median NO and IL-6 levels were significantly higher in women with the METS as compared to controls (p < 0.05). Independent of presenting the METS, analytes were higher in those displaying abdominal obesity (IL-6), hypertension (IL-6 and TNF-α) and more METS diagnostic criteria and abnormal HDL-C, TG and glucose levels (NO). Both cytokines positively correlated with the number of METS criteria, age and time since menopause, IL-6 positively with waist circumference and TNF-α positively with blood pressure levels. NO levels inversely correlated with HDL-C values and positively with the number of METS criteria, glucose, and TG levels; correlation with the latter being the highest (r2 = 0.65, p = 0.0001). Conclusion: Postmenopausal women with the METS displayed higher IL-6 and NO levels, with significant correlations found between studied analytes and some of the components of the syndrome.

[1]  P. Chedraui,et al.  Why sex matters: the biological mechanisms of cardiovascular disease , 2012, Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology.

[2]  M. Siervo,et al.  In vivo nitric oxide synthesis, insulin sensitivity, and asymmetric dimethylarginine in obese subjects without and with metabolic syndrome. , 2012, Metabolism: clinical and experimental.

[3]  T. Postolache,,et al.  Link between leptin and interleukin-6 levels in the initial phase of obesity related inflammation. , 2012, Translational research : the journal of laboratory and clinical medicine.

[4]  S. Thériault,et al.  Linking preeclampsia and cardiovascular disease later in life , 2011, Clinical chemistry and laboratory medicine.

[5]  P. Chedraui,et al.  Pro-inflammatory cytokine levels in postmenopausal women with the metabolic syndrome , 2011, Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology.

[6]  M. Siervo,et al.  In-vivo nitric oxide synthesis is reduced in obese patients with metabolic syndrome: application of a novel stable isotopic method , 2011, Journal of hypertension.

[7]  Archana Singh,et al.  Intergenotypic variation of nitric oxide and inflammatory markers in preeclampsia: a pilot study in a North Indian population. , 2011, Human immunology.

[8]  B. Gustafson Adipose tissue, inflammation and atherosclerosis. , 2010, Journal of atherosclerosis and thrombosis.

[9]  A. Prończuk,et al.  Nutritional correlates and dynamics of diabetes in the Nile rat (Arvicanthis niloticus): a novel model for diet-induced type 2 diabetes and the metabolic syndrome , 2010, Nutrition & metabolism.

[10]  E. Maury,et al.  Adipokine dysregulation, adipose tissue inflammation and metabolic syndrome , 2010, Molecular and Cellular Endocrinology.

[11]  S. Grundy,et al.  Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International As , 2009, Circulation.

[12]  P. Chedraui,et al.  Cardiovascular risk in menopausal women and prevalent related co-morbid conditions: facing the post-Women's Health Initiative era. , 2009, Fertility and sterility.

[13]  A. Falus,et al.  The major inflammatory mediator interleukin-6 and obesity , 2009, Inflammation Research.

[14]  P. Chedraui,et al.  Plasma and placental nitric oxide levels in women with and without pre‐eclampsia living at different altitudes , 2009, International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics.

[15]  S. Grundy Metabolic Syndrome Pandemic , 2008, Arteriosclerosis, thrombosis, and vascular biology.

[16]  A. Hingorani,et al.  Pre-eclampsia and risk of cardiovascular disease and cancer in later life: systematic review and meta-analysis , 2007, BMJ : British Medical Journal.

[17]  M. Quon,et al.  Vascular and metabolic effects of candesartan: insights from therapeutic interventions , 2006, Journal of hypertension. Supplement : official journal of the International Society of Hypertension.

[18]  A. Schechter,et al.  Plasma nitrite concentrations reflect the degree of endothelial dysfunction in humans. , 2006, Free radical biology & medicine.

[19]  S. Moncada,et al.  The discovery of nitric oxide and its role in vascular biology , 2006, British journal of pharmacology.

[20]  P. Chedraui,et al.  The metabolic syndrome among postmenopausal women in Ecuador , 2006, Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology.

[21]  Paul Zimmet,et al.  The metabolic syndrome—a new worldwide definition , 2005, The Lancet.

[22]  R. Ness,et al.  Early Occurrence of Metabolic Syndrome After Hypertension in Pregnancy , 2005, Obstetrics and gynecology.

[23]  J. Blümel,et al.  Age, menopause and hormone replacement therapy influences on cardiovascular risk factors in a cohort of middle-aged Chilean women. , 2003, Maturitas.

[24]  J. Mckenney,et al.  National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) , 2002 .

[25]  L Wood,et al.  Adipose tissue tumor necrosis factor and interleukin-6 expression in human obesity and insulin resistance. , 2001, American journal of physiology. Endocrinology and metabolism.

[26]  T. Gotoh,et al.  Regulation of nitric oxide production by arginine metabolic enzymes. , 2000, Biochemical and biophysical research communications.

[27]  W. Daniel,et al.  Decreased plasma concentrations of L-hydroxy-arginine as a marker of reduced NO formation in patients with combined cardiovascular risk factors. , 2000, The Journal of laboratory and clinical medicine.

[28]  S. Blankenberg,et al.  Inflammatory markers and cardiovascular risk in the metabolic syndrome. , 2011, Frontiers in bioscience.

[29]  Roger J. R. Levesque,et al.  Obesity and Overweight , 2011 .

[30]  N. Unwin,et al.  Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) Detection, Evaluation, and Treatment of High Blood Cholesterol Education Program (NCEP) Expert Panel on Executive Summary of the Third Report of the National , 2009 .

[31]  M. de Oya [Inflammation and metabolic syndrome]. , 2004, Medicina clinica.

[32]  M. Cushman,et al.  Menopause-related differences in inflammation markers and their relationship to body fat distribution and insulin-stimulated glucose disposal. , 2002, Fertility and sterility.

[33]  S. Grundy,et al.  National Cholesterol Education Program Third Report of the National Cholesterol Education Program ( NCEP ) Expert Panel on Detection , Evaluation , and Treatment of High Blood Cholesterol in Adults ( Adult Treatment Panel III ) Final Report , 2022 .