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Increase HDL-C level over the menopausal transition is associated with greater atherosclerotic progression.

ABSTRACT: Experimental and observational evidence demonstrates that high-density lipoprotein (HDL) can lose its well-documented atheroprotective functions and even adopt a paradoxically proinflammatory nature in certain conditions. Hormonal alterations, especially estradiol reduction, influence the accumulation of risk factors that could potentially impair the quality of HDL during the menopausal transition (MT). Limited data exist to evaluate the relationship between changes in HDL-cholesterol (HDL-C) and its main carried protein, apolipoprotein A (apoA), over the MT, and atherosclerosis development.To evaluate the associations of changes in HDL-C and apoA with progression of carotid intima-media thickness (cIMT), carotid adventitial diameter (cAD), and presence of carotid plaque relative to the onset of the postmenopause.A total of 213 participants (age [mean (SD)]: 45.7 [2.5] years at baseline; 70% white) from the Study of Women's Health Across the Nation Pittsburgh site were included. Participants had up to 5 measures of cIMT, cAD, and carotid plaque over a maximum of 9 years of follow-up.Adjusting for sociodemographic, cardiovascular disease risk factors, cardiovascular disease medication use, and C-reactive protein, a larger increase in HDL-C since baseline was significantly associated with a greater cIMT progression (P = .008). Additionally, a higher apoA level at baseline was significantly associated with a lower cIMT progression (P = .03). No significant associations were found with cAD or plaque presence.As women transition through menopause, increases in HDL-C levels are independently associated with greater cIMT progression. Thus, the quality of HDL may be altered over the MT rendering HDL dysfunctional and not providing the expected cardioprotective effect.

SUBMITTER: El Khoudary SR

PROVIDER: S-EPMC5010007 | biostudies-literature | 2016 Jul-Aug

REPOSITORIES: biostudies-literature

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Increase HDL-C level over the menopausal transition is associated with greater atherosclerotic progression.

El Khoudary Samar R SR Wang Lin L Brooks Maria M MM Thurston Rebecca C RC Derby Carol A CA Matthews Karen A KA

Journal of clinical lipidology 20160426 4

<h4>Background</h4>Experimental and observational evidence demonstrates that high-density lipoprotein (HDL) can lose its well-documented atheroprotective functions and even adopt a paradoxically proinflammatory nature in certain conditions. Hormonal alterations, especially estradiol reduction, influence the accumulation of risk factors that could potentially impair the quality of HDL during the menopausal transition (MT). Limited data exist to evaluate the relationship between changes in HDL-cho ...[more]

PMID: 27578129

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Project description:OBJECTIVE:HDL (high-density lipoprotein) infusion reduces atherosclerosis in animal models and is being evaluated as a treatment in humans. Studies have shown either anti- or proinflammatory effects of HDL in macrophages, and there is no consensus on the underlying mechanisms. Here, we interrogate the effects of HDL on inflammatory gene expression in macrophages. Approach and Results: We cultured bone marrow-derived macrophages, treated them with reconstituted HDL or HDL isolated from APOA1Tg;Ldlr-/- mice, and challenged them with lipopolysaccharide. Transcriptional profiling showed that HDL exerts a broad anti-inflammatory effect on lipopolysaccharide-induced genes and proinflammatory effect in a subset of genes enriched for chemokines. Cholesterol removal by POPC (1-palmitoyl-2-oleoyl-glycero-3-phosphocholine) liposomes or β-methylcyclodextrin mimicked both pro- and anti-inflammatory effects of HDL, whereas cholesterol loading by POPC/cholesterol-liposomes or acetylated LDL (low-density lipoprotein) before HDL attenuated these effects, indicating that these responses are mediated by cholesterol efflux. While early anti-inflammatory effects reflect reduced TLR (Toll-like receptor) 4 levels, late anti-inflammatory effects are due to reduced IFN (interferon) receptor signaling. Proinflammatory effects occur late and represent a modified endoplasmic reticulum stress response, mediated by IRE1a (inositol-requiring enzyme 1a)/ASK1 (apoptosis signal-regulating kinase 1)/p38 MAPK (p38 mitogen-activated protein kinase) signaling, that occurs under conditions of extreme cholesterol depletion. To investigate the effects of HDL on inflammatory gene expression in myeloid cells in atherosclerotic lesions, we injected reconstituted HDL into Apoe-/- or Ldlr-/- mice fed a Western-type diet. Reconstituted HDL infusions produced anti-inflammatory effects in lesion macrophages without any evidence of proinflammatory effects. CONCLUSIONS:Reconstituted HDL infusions in hypercholesterolemic atherosclerotic mice produced anti-inflammatory effects in lesion macrophages suggesting a beneficial therapeutic effect of HDL in vivo.

Dataset Information

Increase HDL-C level over the menopausal transition is associated with greater atherosclerotic progression.

Publications

Increase HDL-C level over the menopausal transition is associated with greater atherosclerotic progression.

Similar Datasets

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