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HDL (High-Density Lipoprotein) Metrics and Atherosclerotic Risk in Women.

ABSTRACT: Objective- HDL-C (high-density lipoprotein cholesterol) may not always be cardioprotective in postmenopausal women. HDL particles (HDL-P) via ion-mobility may better reflect the antiatherogenicity of HDL. Objectives were (1) to evaluate associations of HDL-C and ion-mobility HDL-P with carotid intima-media thickness (cIMT) and carotid plaque separately and jointly in women; and (2) to assess interactions by age at and time since menopause. Approach and Results- Analysis included 1380 females from the MESA (Multi-Ethnic Study of Atherosclerosis; age: 61.8±10.3; 61% natural-, 21% surgical-, and 18% peri-menopause). Women with unknown or early menopause (age at nonsurgical menopause ?45 years) were excluded. Adjusting for each other, higher HDL-P but not HDL-C was associated with lower cIMT ( P=0.001), whereas higher HDL-C but not HDL-P was associated with greater risk of carotid plaque presence ( P=0.04). Time since menopause significantly modified the association of large but not small HDL-P with cIMT; higher large HDL-P was associated with higher cIMT close to menopause but with lower cIMT later in life. The proatherogenic association reported for HDL-C with carotid plaque was most evident in women with later age at menopause who were >10 years postmenopausal. Conclusions- Elevated HDL-C may not always be cardioprotective in postmenopausal women. The cardioprotective capacity of large HDL-P may adversely compromise close to menopause supporting the importance of assessing how the menopause transition might impact HDL quality and related cardiovascular disease risk later in life.

SUBMITTER: El Khoudary SR

PROVIDER: S-EPMC6202150 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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HDL (High-Density Lipoprotein) Metrics and Atherosclerotic Risk in Women.

El Khoudary Samar R SR Ceponiene Indre I Samargandy Saad S Stein James H JH Li Dong D Tattersall Matthew C MC Budoff Matthew J MJ

Arteriosclerosis, thrombosis, and vascular biology 20180901 9

Objective- HDL-C (high-density lipoprotein cholesterol) may not always be cardioprotective in postmenopausal women. HDL particles (HDL-P) via ion-mobility may better reflect the antiatherogenicity of HDL. Objectives were (1) to evaluate associations of HDL-C and ion-mobility HDL-P with carotid intima-media thickness (cIMT) and carotid plaque separately and jointly in women; and (2) to assess interactions by age at and time since menopause. Approach and Results- Analysis included 1380 females fro ...[more]

PMID: 30026268

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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

HDL (High-Density Lipoprotein) Metrics and Atherosclerotic Risk in Women.

Publications

HDL (High-Density Lipoprotein) Metrics and Atherosclerotic Risk in Women.

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