Circulating tryptase as a marker for subclinical atherosclerosis in obese subjects.
BACKGROUND
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.
Department of Diabetes, Endocrinology and Nutrition, Institut d'Investigació Biomèdica de Girona (IdIBGi), CIBEROBN (CB06/03/010) and Instituto de Salud Carlos III (ISCIII), Girona, Spain.
María
M
Moreno
Department of Radiology, Institut d'Investigació Biomèdica de Girona (IdIBGi), CIBEROBN (CB06/03/010) and Instituto de Salud Carlos III (ISCIII), Girona, Spain.
Josep
J
Puig
Department of Diabetes, Endocrinology and Nutrition, Institut d'Investigació Biomèdica de Girona (IdIBGi), CIBEROBN (CB06/03/010) and Instituto de Salud Carlos III (ISCIII), Girona, Spain.
Marta
M
Serrano
Department of Diabetes, Endocrinology and Nutrition, Institut d'Investigació Biomèdica de Girona (IdIBGi), CIBEROBN (CB06/03/010) and Instituto de Salud Carlos III (ISCIII), Girona, Spain.
José María
JM
Moreno-Navarrete
Department of Diabetes, Endocrinology and Nutrition, Institut d'Investigació Biomèdica de Girona (IdIBGi), CIBEROBN (CB06/03/010) and Instituto de Salud Carlos III (ISCIII), Girona, Spain.
Francisco
F
Ortega
Department of Diabetes, Endocrinology and Nutrition, Institut d'Investigació Biomèdica de Girona (IdIBGi), CIBEROBN (CB06/03/010) and Instituto de Salud Carlos III (ISCIII), Girona, Spain.
Wifredo
W
Ricart
Department of Diabetes, Endocrinology and Nutrition, Institut d'Investigació Biomèdica de Girona (IdIBGi), CIBEROBN (CB06/03/010) and Instituto de Salud Carlos III (ISCIII), Girona, Spain.
Jose Manuel
JM
Fernandez-Real
D000328:Adult; D000368:Aged; D000886:Anthropometry; D050197:Atherosclerosis / Q000097:blood* / Q000150:complications / Q000175:diagnosis* / Q000000981:diagnostic imaging; D001823:Body Composition; D059168:Carotid Intima-Media Thickness; D008076:Cholesterol, HDL / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006454:Hemoglobins / Q000737:chemistry; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000150:complications*; D016133:Polymerase Chain Reaction; D012372:ROC Curve; D012044:Regression Analysis; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood; D053802:Tryptases / Q000097:blood*
D008076:Cholesterol, HDL; D006454:Hemoglobins; D014280:Triglycerides; D053802:Tryptases