Alterations in Adhesion Molecules, Pro-Inflammatory Cytokines and Cell-Derived Microparticles Contribute to Intima-Media Thickness and Symptoms in Postmenopausal Women

Abstract

Menopause, the cessation of menses, occurs with estrogens decline, low-grade inflammation, and impaired endothelial function, contributing to atherosclerotic risk. Intima-media thickness (IMT) is an early subclinical biomarker of atherosclerosis. Inflammation may have a role on symptoms: hot flashes, anxiety, and depressive mood, which also are related to endothelial dysfunction, increased IMT and cardiovascular risk. In this study we compared several inflammatory markers in early vs. late postmenopausal women and studied the association of IMT and symptoms with these markers in the full sample. In a cross-sectional design including 60 women (53.1±4.4 years old) at early and late postmenopause, we evaluated the expression of CD62L, ICAM-1, PSGL-1, CD11b, CD11c, and IL-8R on PBMC by flow cytometry. Serum soluble ICAM-1, sVCAM-1, sCD62E, sCD62P, CXCL8, IL-1β, IL-6, and TNF-α levels were quantified by ELISA. Plasma levels of microparticles (MPs) were determined by FACS. Finally, carotid intima-media thickness (IMT) was measured by ultrasound. We observed that ICAM-1 expression by lymphocytes and serum sVCAM-1 levels were augmented at late postmenopause. Late postmenopause women with severe hot flashes had increased expression of CD62L and IL-8R on neutrophils. By multivariate analysis, the carotid IMT was strongly associated with membrane-bound TNF-α, CD11b expression, Annexin V+ CD3+ MPs, LPS-induced NO production, HDL-cholesterol and age. Depressive mood was associated negatively with PSGL-1 and positively with LPS-induced NO. Finally, Log(AMH) levels were associated with carotid IMT, IL-8R expression and time since menopause. IMT and depressive mood were the main clinical features related to vascular inflammation. Aging, hormonal changes and obesity were also related to endothelial dysfunction. These findings provide further evidence for a link between estrogen deficiency and low-grade inflammation in endothelial impairment in mature women.

Sex Differences in Depression: Does Inflammation Play a Role?

“…As reproductive hormones rise and fall during the menstrual cycle in premenopausal women, corresponding changes in CRP occur [92]. During menopausal transition (i.e., perimenopause), women experience more pronounced hormonal fluctuations, subsequently resulting in diminished estrogen levels following menopause [91, 93]. Due partially to low estrogen levels, postmenopausal women experience elevated inflammation, which may affect women’s health during aging [93–95].…”

“…During menopausal transition (i.e., perimenopause), women experience more pronounced hormonal fluctuations, subsequently resulting in diminished estrogen levels following menopause [91, 93]. Due partially to low estrogen levels, postmenopausal women experience elevated inflammation, which may affect women’s health during aging [93–95]. Indeed, estrogen typically inhibits inflammation, and inflammatory processes play a role in atherosclerosis, cardiovascular disease, and other age-related diseases later in life [94, 96, 97].…”

Basal neutrophil function in human aging: Implications in endothelial cell adhesion

“…Interestingly, increased CD11b levels have been associated with hypertension, a condition of high prevalence in the elderly population (Rea et al, 2013). Also, a study conducted with postmenopausal women showed a strong positive correlation of carotid intima-media thickness with CD11b expression and membrane-bound TNF-a (Figueroa-Vega et al, 2015), strengthening the connection between CD11b levels and pro-inflammatory parameters, leading to cardiovascular risk factors. Overall, increased CD11b is associated with higher adhesive response of stimulated neutrophils, even though the effectiveness of their migration and function may not be preserved with age (Wessels et al, 2010).…”

Predictors of Subclinical Inflammatory Obesity: Plasma Levels of Leptin, Very Low-Density Lipoprotein Cholesterol and CD14 Expression of CD16+ Monocytes

“…CD11b has been associated with high-fat diet-induced obesity [37], and carotid intima-media thickness [38], and CD11b expression was described as lowest for non-classical monocytes after lipopolysaccharide stimulation [39] and in a rodent model of type 2 diabetes [40]. Results concerning CD36 atherogenicity are also contradictory since an increase [35] or deficiency [41] of its expression have been associated with the pathogenesis of atherosclerosis and CVD.…”