Evidence of proatherogenic inflammation in polycystic ovary syndrome.
Women with polycystic ovary syndrome (PCOS) have chronic low-level inflammation that can increase the risk of atherogenesis. We measured circulating proatherogenic inflammatory mediators in women with PCOS (8 lean: body mass index, 18-25 kg/m(2); 8 obese: body mass index, 30-40 kg/m(2)) and weight-matched controls (8 lean, 8 obese). Blood samples were obtained fasting and 2 hours after glucose ingestion to measure interleukin-6 (IL-6), soluble intercellular adhesion molecule-1 (sICAM-1), monocyte chemotactic protein-1 (MCP-1), C-reactive protein (CRP), matrix metalloproteinase-2, plasminogen activator inhibitor-1 (PAI-1), and activated nuclear factor kappaB in mononuclear cells. Truncal fat was determined by dual-energy x-ray absorptiometry. Fasting MCP-1 levels were elevated in lean women with PCOS compared with lean controls (159.9 +/- 14.1 vs 121.2 +/- 5.4 pg/mL, P < .02). Hyperglycemia failed to suppress matrix metalloproteinase-2 in lean women with PCOS compared with lean controls (1.7 +/- 1.2 vs -4.8 +/- 1.6 pg/mL, P < .002). Among women with PCOS, obese individuals exhibited higher fasting sICAM-1 (16.1 +/- 0.8 vs 10.5 +/- 1.0 ng/mL, P < .03) and PAI-1 (6.1 +/- 0.7 vs 3.4 +/- 0.8 ng/mL, P < .03) levels. Trend analysis revealed higher (P < .005) IL-6, sICAM-1, CRP, PAI-1, systolic and diastolic blood pressures, triglycerides, fasting insulin, and homeostasis model assessment of insulin resistance index in women with PCOS compared with weight-matched controls, and the highest levels in the obese regardless of PCOS status. Fasting MCP-1 levels correlated with activated nuclear factor kappaB during hyperglycemia (P < .05) and androstenedione (P < .004). Truncal fat correlated with fasting IL-6 (P < .004), sICAM-1 (P < .006), CRP (P < .0009), and PAI-1 (P < .02). We conclude that both PCOS and obesity contribute to a proatherogenic state; but in women with PCOS, abdominal adiposity and hyperandrogenism may exacerbate the risk of atherosclerosis.
González
Frank
F
Department of Obstetrics and Gynecology, College of Medicine, Mayo Clinic, Rochester, MN 55905, USA. gonzalez.frank@mayo.edu
Rote
Neal S
NS
Minium
Judi
J
Kirwan
John P
JP
D015502:Absorptiometry, Photon; D000328:Adult; D000728:Androgens / Q000097:blood; D050197:Atherosclerosis / Q000097:blood / Q000473:pathology*; D002097:C-Reactive Protein / Q000378:metabolism; D018932:Chemokine CCL2 / Q000097:blood; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D020778:Matrix Metalloproteinase 2 / Q000097:blood; D016328:NF-kappa B / Q000097:blood; D009765:Obesity / Q000097:blood / Q000473:pathology*; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D011085:Polycystic Ovary Syndrome / Q000097:blood / Q000473:pathology*; D055815:Young Adult
D000728:Androgens; D018932:Chemokine CCL2; D015850:Interleukin-6; D016328:NF-kappa B; D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human; D018799:Intercellular Adhesion Molecule-1; D002097:C-Reactive Protein; D020778:Matrix Metalloproteinase 2