Altered Protein Composition of Subcutaneous Adipose Tissue in Chronic Kidney Disease

被引:15
作者
Gertow, Joanna [1 ]
Ng, Chang Zhi [1 ]
Branca, Rui Miguel Mamede [2 ,3 ]
Werngren, Olivera [1 ]
Du, Lei [1 ]
Kjellqvist, Sanela [4 ]
Hemmingsson, Peter [5 ]
Bruchfeld, Annette [5 ]
MacLaughlin, Helen [6 ,7 ]
Eriksson, Per [1 ]
Axelsson, Jonas [8 ]
Fisher, Rachel M. [1 ]
机构
[1] Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, Ctr Mol Med, Stockholm, Sweden
[2] Sci Life Lab, Dept Oncol Pathol, Clin Prote Mass Spectrometry, Stockholm, Sweden
[3] Karolinska Inst, Stockholm, Sweden
[4] Stockholm Univ, Dept Biochem & Biophys, Sci Life Lab, Stockholm, Sweden
[5] Karolinska Inst, Dept Clin Sci Intervent & Technol CLINTEC, Stockholm, Sweden
[6] Kings Coll London, Div Diabet & Nutr Sci, London, England
[7] Kings Coll Hosp London, London, England
[8] Karolinska Inst, Dept Med Biochem & Biophys, Stockholm, Sweden
基金
瑞典研究理事会;
关键词
adipose tissue; alpha-1-microglobulin/bikunin precursor; cardiovascular disease; chronic kidney disease; proteomics; vimentin; INSULIN-RESISTANCE; ADIPOCYTE SIZE; FATTY-ACIDS; INFLAMMATION; ADIPOKINES; LIPOLYSIS; SURVIVAL; HEMODIALYSIS; DYSFUNCTION; ACTIVATION;
D O I
10.1016/j.ekir.2017.07.007
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Introduction: Loss of renal function is associated with high mortality from cardiovascular disease (CVD). Patients with chronic kidney disease (CKD) have altered circulating adipokine and nonesterified fatty acid concentrations and insulin resistance, which are features of disturbed adipose tissue metabolism. Because dysfunctional adipose tissue contributes to the development of CVD, we hypothesize that adipose tissue dysfunctionality in patients with CKD could explain, at least in part, their high rates of CVD. Therefore we characterized adipose tissue from patients with CKD, in comparison to healthy controls, to search for signs of dysfunctionality. Methods: Biopsy samples of subcutaneous adipose tissue from 16 CKD patients and 11 healthy controls were analyzed for inflammation, fibrosis, and adipocyte size. Protein composition was assessed using 2dimensional gel proteomics combined with multivariate analysis. Results: Adipose tissue of CKD patients contained significantly more CD68-positive cells, but collagen content did not differ. Adipocyte size was significantly smaller in CKD patients. Proteomic analysis of adipose tissue revealed significant differences in the expression of certain proteins between the groups. Proteins whose expression differed the most were a-1-microglobulin/ bikunin precursor (AMBP, higher in CKD) and vimentin (lower in CKD). Vimentin is a lipid droplet-associated protein, and changes in its expression may impair fatty acid storage/mobilization in adipose tissue, whereas high levels of AMBP may reflect oxidative stress. Discussion: These findings demonstrate that adipose tissue of CKD patients shows signs of inflammation and disturbed functionality, thus potentially contributing to the unfavorable metabolic profile and increased risk of CVD in these patients.
引用
收藏
页码:1208 / 1218
页数:11
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