Role of long non-coding RNAs expression (ANRIL, NOS3-AS, and APOA1-AS) in development of atherosclerosis in Egyptian systemic lupus erythematosus patients

Clin Rheumatol. 2018 Dec;37(12):3319-3328. doi: 10.1007/s10067-018-4269-x. Epub 2018 Aug 21.

Abstract

To quantify the expression level of three lncRNAs which are known to be relevant to atherosclerosis (ANRIL, NOS3-AS, and APOA1-AS) in SLE patients and to assess their relationship with atherogenic and inflammatory biomarkers. The circulating levels of these lncRNAs were assessed using RT-PCR, in addition to measurement of E-selectin, V-CAM1, oxidized low-density lipoprotein (oxLDL), total nitric oxide (NOx), and lipid profile in 65 SLE patients (35 atherosclerotic and 30 non-atherosclerotic) and 35 healthy subjects. The expression levels of these lncRNAs were higher in SLE patients than in healthy controls. Importantly, a higher overexpression of these lncRNAs was noticed in atherosclerotic SLE patients than in non-atherosclerotic ones. In atherosclerotic SLE patients, level of ANRIL was positively associated with menopause, SLE duration, SLEDAI, and SLICC and negatively correlated with C3. Moreover, NOS3-AS expression was negatively correlated with total NOx level and HDL, while it was positively correlated with TC, LDL-C, hypertension, metabolic syndrome, obesity and dyslipidemia, CIMT, VCAM-1, E-selectin, oxLDL, SLEDAI, and SLICC. With respect to APOA1-AS, its expression was negatively correlated with HDL-C, whereas it was positively correlated with TC, LDL-C, hypertension, dyslipidemia, obesity, metabolic syndrome, menopause, CIMT, RI, V-CAM1, E-selectin, oxLDL, and SLICC. ANRIL, NOS3-AS, and APOA1-AS could be used as predictive biomarkers for atherosclerosis in SLE. Multivariate analyses identified these lncRNAs as independent predictors for atherosclerosis in SLE. These lncRNAs play a pivotal role in development of atherosclerosis via their significant repercussions atherogenic and inflammatory indices.

Keywords: ANRIL; APOA1-AS; Atherosclerosis; NOS3-AS; Non-coding RNAs; SLE.

MeSH terms

  • Adolescent
  • Adult
  • Apolipoprotein A-I / genetics*
  • Atherosclerosis / complications
  • Atherosclerosis / genetics*
  • Body Mass Index
  • Case-Control Studies
  • E-Selectin / genetics
  • Egypt / epidemiology
  • Female
  • Gene Expression Profiling*
  • Humans
  • Inflammation
  • Lipoproteins, LDL / metabolism
  • Lupus Erythematosus, Systemic / complications
  • Lupus Erythematosus, Systemic / genetics*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Nitric Oxide Synthase Type III / genetics*
  • Prognosis
  • RNA, Long Noncoding / genetics*
  • ROC Curve
  • Risk Factors
  • Young Adult

Substances

  • APOA1 protein, human
  • Apolipoprotein A-I
  • CDKN2B antisense RNA, human
  • E-Selectin
  • Lipoproteins, LDL
  • RNA, Long Noncoding
  • oxidized low density lipoprotein
  • NOS3 protein, human
  • Nitric Oxide Synthase Type III