Circulating tryptase as a marker for subclinical atherosclerosis in obese subjects.

María Moreno,Josep Puig,Francisco Ortega,Marta Serrano,Jose Manuel Fernandez-Real,José María Moreno-Navarrete,Wifredo Ricart,Christian Schulz

doi:10.1371/journal.pone.0097014

Abstract

IntroductionMast 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.MethodsCirculating tryptase levels (ELISA) and metabolic parameters were analyzed in 228 subjects. Atherosclerosis (c-IMT>0.9 mm) was evaluated ultrasonographically.ResultsSignificant 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 asociation 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).ConclusionsCirculating 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.

Highlights

Mast cells participate in atherogenesis by releasing cytokines to induce vascular cell protease expression
The purpose of our study was to investigate the association between circulating tryptase levels and subclinical atherosclerosis through estimation of carotid intima-media thickness (c-IMT) as a surrogate marker for increased cardiovascular risk
Significant positive associations were evident between circulating tryptase levels and body mass index (BMI), fat mass, glycated haemoglobin, fasting insulin, homeostasis model assessment of insulin resistance (HOMAIR), fasting triglycerides and ultrasensitive PCR

Summary

Introduction

Mast cells participate in atherogenesis by releasing cytokines to induce vascular cell protease expression. Atherosclerosis is a chronic inflammatory disease that is the main cause of cardiovascular morbidity and mortality all over the world It is characterized by the progressive accumulation of cholesterol in the intimal layer of arterial walls of large- and medium-sized arteries, leading to the formation of plaques and vascular obstruction [1,2]. Inflammatory cells such as lymphocytes, macrophages, neutrophils, and mast cells are involved in the pathogenesis of atherosclerotic plaque rupture, as they cause the fibrous plaque to weaken because of the enzyme activity of the leukocytes that degrade the extracellular matrix [3]. These proteases were found in the human arterial intima twenty years ago, both normal and atherosclerotic [7]

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