HDL enrichment in apo A-IV favours its functionality in diabetic kidney disease

A doença renal diabética (DRD) está associada a distúrbios lipídicos que pioram a função renal e aumentam o risco cardiovascular (CV). O manejo da dislipidemia, hipertensão e outros fatores de risco tradicionais não impede completamente as complicações CV, trazendo à tona a participação de fatores de risco não-tradicionais, como produtos de glicação avançada (AGE), de carbamoilação e alterações no proteoma e na funcionalidade da HDL. Avaliou-se, no presente estudo, a composição da HDL, seu proteoma, modificação química por glicação e carbamoilação e sua funcionalidade em indivíduos com DRD não-dialítica, categorizados de acordo com a taxa de filtração glomerular (TFG) e a taxa de excreção urinária de albumina (EUA) em controles não- diabéticos. Os indivíduos com DRD foram divididos em TFG > 60 mL / min / 1,73 m2 + A1 ( 300 mg/g de creatinina) (n = 25) e pareados por idade com indivíduos controles com TFG > 60; (n = 8). As HDL foram isoladas do plasma por ultracentrifugação e as dosagens bioquímicas de lípides realizadas por métodos enzimáticos; carboximetil- lisina (CML) e carbamoilação por ELISA. AGE total e pentosidina foram determinados por análise fluorimétrica. As HDL foram utilizadas para medir a remoção de 14C-colesterol de macrófagos; para inibição da oxidação de LDL, induzida por solução de sulfato de cobre e para modular a secreção de citocinas inflamatórias em macrófagos estimulados com lipopolissacarídeos. A HDL do grupo TFG 60 mL/min/1.73 m2 plus AER stages A1 ( 300 mg/g creatinine( (n=25) and control subjects matched by age with (GFR > 60; n=8). HDL was isolated from plasma by ultracentrifugation and biochemical analysis performed by enzymatic techniques; carboxymethyllysine and carbamoylation by ELISA. Total AGE and pentosidine were determined by fluorimetry. HDL was utilized to measure 14C-cholesterol removal from macrophages, the inhibition of LDL oxidation induced by cooper sulfate and the modulation of cytokines secretion by LPS-challenged macrophages. HDL from GFR < 60+A3 presented higher levels of total AGE, pentosidine and carbamoylation (1.2, 1.1 and 4.2 times, respectively) in comparison to controls. The amount of phospholipids and apoA-I was reduced in this group as compared to control. Targeted proteomic analyses quantified 29 proteins associated with HDL in all groups, although only 2 were more expressed in GFR < 60+A3 group in comparison to controls: apolipoprotein D (apoD) and apoA-IV. As compared to controls, the HDL-mediated cholesterol efflux from macrophages was 33% reduced in GFR < 60+A3 although HDL from this group inhibited 95% the secretion of IL-6 and TNF-alpha. The antioxidant role of HDL (lag time for LDL oxidation) was similar among groups. The increment in apoA-IV that presents many antiatherogenic actions seems to counteract the HDL chemical modification by advanced glycation and carbamoylation and its increment in apoD that occurs in well-established DKD according to the increase in AER and reduction in GF

Increased Expression of miR-223-3p and miR-375-3p and Anti-Inflammatory Activity in HDL of Newly Diagnosed Women in Advanced Stages of Breast Cancer

The expression of inflammation-related miRs bound to high-density lipoproteins (HDLs), the anti-inflammatory activity of HDLs isolated from individuals with breast cancer, and controls were determined. Forty newly diagnosed women with breast cancer naïve of treatment and 10 control participants were included. Cholesterol-loaded bone-marrow-derived macrophages were incubated with HDL from both groups and challenged with lipopolysaccharide (LPS). Interleukin 6 (IL6) and tumor necrosis factor (TNF) in the medium were quantified. The miRs in HDLs were determined by RT-qPCR. Age, body mass index, menopausal status, plasma lipids, and HDL composition were similar between groups. The ability of HDL to inhibit IL6 and TNF production was higher in breast cancer compared to controls, especially in advanced stages of the disease. The miR-223-3p and 375-3p were higher in the HDLs of breast cancer independent of the histological type of the tumor and had a high discriminatory power between breast cancer and controls. The miR-375-3p was greater in the advanced stages of the disease and was inversely correlated with the secretion of inflammatory cytokines. Inflammation-related miRs and the anti-inflammatory role of HDLs may have a significant impact on breast cancer pathophysiology