Implication of progranulin and C1q/TNF-related protein-3 (CTRP3) on inflammation and atherosclerosis in subjects with or without metabolic syndrome

PLoS One. 2013;8(2):e55744. doi: 10.1371/journal.pone.0055744. Epub 2013 Feb 7.

Abstract

Objective: Progranulin and C1q/TNF-related protein-3 (CTRP3) were recently discovered as novel adipokines which may link obesity with altered regulation of glucose metabolism, chronic inflammation and insulin resistance.

Research design and methods: We examined circulating progranulin and CTRP3 concentrations in 127 subjects with (n = 44) or without metabolic syndrome (n = 83). Furthermore, we evaluated the relationship of progranulin and CTRP3 levels with inflammatory markers and cardiometabolic risk factors, including high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), estimated glomerular filtration rate (eGFR), and adiponectin serum concentrations, as well as carotid intima-media thickness (CIMT).

Results: Circulating progranulin levels are significantly related with inflammatory markers, hsCRP (r = 0.30, P = 0.001) and IL-6 (r = 0.30, P = 0.001), whereas CTRP3 concentrations exhibit a significant association with cardiometabolic risk factors, including waist circumference (r = -0.21), diastolic blood pressure (r = -0.21), fasting glucose (r = -0.20), triglyceride (r = -0.34), total cholesterol (r = -0.25), eGFR (r = 0.39) and adiponectin (r = 0.26) levels. Serum progranulin concentrations were higher in patients with metabolic syndrome than those of the control group (199.55 [179.33, 215.53] vs. 185.10 [160.30, 204.90], P = 0.051) and the number of metabolic syndrome components had a significant positive correlation with progranulin levels (r = 0.227, P = 0.010). In multiple regression analysis, IL-6 and triglyceride levels were significant predictors of serum progranulin levels (R(2) = 0.251). Furthermore, serum progranulin level was an independent predictor for increased CIMT in subjects without metabolic syndrome after adjusting for other cardiovascular risk factors (R(2) = 0.365).

Conclusions: Serum progranulin levels are significantly associated with systemic inflammatory markers and were an independent predictor for atherosclerosis in subjects without metabolic syndrome.

Trial registration: ClinicalTrials.gov NCT01668888.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Atherosclerosis / blood*
  • Atherosclerosis / complications
  • Biomarkers / blood
  • Case-Control Studies
  • Female
  • Humans
  • Inflammation / blood*
  • Inflammation / complications
  • Intercellular Signaling Peptides and Proteins / blood*
  • Male
  • Metabolic Syndrome / blood*
  • Metabolic Syndrome / complications
  • Middle Aged
  • Progranulins
  • Risk Factors
  • Tumor Necrosis Factors / blood*

Substances

  • Biomarkers
  • C1QTNF3 protein, human
  • GRN protein, human
  • Intercellular Signaling Peptides and Proteins
  • Progranulins
  • Tumor Necrosis Factors

Associated data

  • ClinicalTrials.gov/NCT01668888

Grants and funding

Dr. KMC was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2012006363) and Drs. SHB and KMC were supported by the Brain Korea 21 Project of the Ministry of Education and Human Resources Development, Republic of Korea (A102065-1011-1070100). Dr. HJY was also supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2012R1A1A1005257). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.