Circulating tryptase as a marker for subclinical atherosclerosis in obese subjects

PLoS One. 2014 May 15;9(5):e97014. doi: 10.1371/journal.pone.0097014. eCollection 2014.

Abstract

Introduction: Mast cells participate in atherogenesis by releasing cytokines to induce vascular cell protease expression. Tryptase is expressed highly in human atherosclerotic lesions and the inhibition of tryptase activity hampers its capacity to maintain cholesterol inside macrophague foam cells. We aimed to investigate the association between circulating tryptase levels and subclinical atherosclerosis through estimation of carotid intima-media thickness (c-IMT) as surrogate marker for increased cardiovascular risk in obese and non-obese subjects.

Methods: Circulating tryptase levels (ELISA) and metabolic parameters were analyzed in 228 subjects. Atherosclerosis (c-IMT>0.9 mm) was evaluated ultrasonographically.

Results: Significant positive associations were evident between circulating tryptase levels and BMI, fat mass, glycated haemoglobin, fasting insulin, HOMAIR, fasting triglycerides and ultrasensitive PCR (p<0.05 from linear-trend ANOVA). The positive association between tryptase levels and insulin resistance parameters, suggested a glucose homeostasis impairment in individuals with higher tryptase levels. The negative association between tryptase levels and HDL-cholesterol supports the proatherogenic role of this protease (p<0.0001). Circulating tryptase levels were strongly associated with c-IMT measurements (p<0.0001 from linear-trend ANOVA), and were higher in subjects with presence of carotid plaque (p<0.0001). Tryptase levels (beta = 0.015, p = 0.001) contributed independently to subclinical atherosclerosis variance after controlling for cardiovascular risk factors (BMI, blood pressure, LDL-cholesterol).

Conclusions: Circulating tryptase level is associated to obesity related parameters and has a close relation with various metabolic risk factors. Moreover, serum tryptase level was independently associated with c-IMT, suggesting its potential use as a surrogate marker for subclinical atherosclerosis in obese subjects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anthropometry
  • Atherosclerosis / blood*
  • Atherosclerosis / complications
  • Atherosclerosis / diagnosis*
  • Atherosclerosis / diagnostic imaging
  • Body Composition
  • Carotid Intima-Media Thickness
  • Cholesterol, HDL / blood
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Gene Expression Regulation, Enzymologic*
  • Hemoglobins / chemistry
  • Humans
  • Male
  • Middle Aged
  • Obesity / blood
  • Obesity / complications*
  • Polymerase Chain Reaction
  • ROC Curve
  • Regression Analysis
  • Risk Factors
  • Triglycerides / blood
  • Tryptases / blood*

Substances

  • Cholesterol, HDL
  • Hemoglobins
  • Triglycerides
  • Tryptases

Grants and funding

This study was supported by the Spanish Ministry of Health (FIS 2011-00214), and CIBERobn Fisiopatología de la Obesidad y la Nutrición (CIBERobn). The CIBER de la Fisiopatología de la Obesidad y Nutrición (CIBERobn) is an initiative from the Instituto de Salud Carlos III (ISCIII). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.