Pilot study of sex differences in chemokine/cytokine markers of atherosclerosis in humans

Background: Atherogenic processes increase in women after menopause, when the risk of cardiovascular adverse events approaches that observed in age-matched men. In experimental animals, ovariectomy increases the platelet content of mitogenic cytokines, such as platelet-derived growth factor (PDGF), which when released into the blood or site of vascular injury, contribute to atherogenic processes. Objective: Experiments were designed to assess the sex distribution of inflammatory chemokines/cytokines, which may be released from platelets in the serum of middle-aged women and men in whom the extent of atherosclerotic coronary disease was defined by coronary arterial calcification (CAC). Methods: Blood was obtained from healthy white individuals recruited from the Mayo Clinic database. CAC was assessed by 64-slice computed tomography. Plasma cholesterol, lipids, and high-sensitivity C-reactive protein were analyzed by the Mayo Clinic Department of Laboratory Medicine and Pathology. Serum cytokines were determined using cytokine arrays. Cytokine expression was measured using dot blot analysis. Results: Of the 16 individuals (I I women, 5 men) who agreed to participate in the study, I woman was premenopausal, 1 was taking oral contraceptives, and 1 was receiving menopausal hormone therapy. One woman had an active infection and was eliminated from the study. CAC was detected in only 2 of the 11 women (scores of 46 and 5 6 Agatston units [AU]) but in 3 of the 5 men (scores of 3, 123, and 609 AU). Correcting for all other risk factors, expression of the chemokine RANTES (regulated on activation, normal, T-cell expressed and secreted; CCL5 [CC chemokine ligand 5]) was 100.98% greater in women than in men, and PDGF-BB was 55.30% greater in women than in men. Conclusions: This small pilot study found that the circulating chemokines/cytokines RANTES and PDGF-BB showed sex-disparate distribution between the women and men studied, and did not appear related to the degree of CAC.