Association Between Matrix Metalloproteinase-10 Concentration and Smoking in Individuals Without Cardiovascular Disease

Introduction and objectivesSmoking is an important cardiovascular risk factor whose underlying mechanism is incompletely understood. However, it has been suggested that alterations in the balance between synthesis and degradation of the extracellular matrix (ECM) may play a role. The aim of this study was to determine whether there is an independent association between smoking and the concentration of circulating metalloproteinases (MMPs) in individuals without cardiovascular disease.MethodsMetabolic parameters, the carotid intima-media thickness (IMT), inflammatory markers (fibrinogen, C-reactive protein and interleukin-6), markers of endothelial damage (eg, von Willebrand factor), and the concentration of MMP-1, −9, and −10 and tissue inhibitor of metalloproteinase-1 (TIMP-1) were assessed in 400 asymptomatic individuals with cardiovascular risk factors. Subjects were divided into non-smokers (n=195), smokers (n=118) and former smokers (n=87). In addition, global cardiovascular risk was determined from PROCAM and REGICOR scores.ResultsBoth MMP-1 and MMP-10 concentrations were significantly higher in smokers than non-smokers (P<.05 and P<.001, respectively), though there was no difference in the levels of MMP-9, TIMP-1, IMT and other inflammatory parameters. There were positive correlations between the MMP-10 concentration and PROCAM and REGICOR scores (P<.001). Multivariate analysis showed that there was still an association between smoking and the MMP-10 concentration after adjustment for age, sex, and other cardiovascular risk factors (P<.001). Multiple regression analysis showed that smoking accounted for 28% of the variability in the MMP-10 concentration.ConclusionsThere was an independent association between smoking and the MMP-10 concentration in asymptomatic individuals. This relationship between MMP-10 and the ECM may indicate a mechanism through which this MMP contributes to smoking-related atherosclerosis.

Introducción y objetivosEl tabaquismo es un importante factor de riesgo cardiovascular cuyo mecanismo no se ha definido con precisión, aunque se ha propuesto que las alteraciones del balance entre síntesis y degradación de la matriz extracelular (MEC) pueden ser relevantes. El objetivo de este estudio es examinar si existe una asociación independiente entre el tabaquismo y la concentración circulante de metaloproteinasas (MMP) en sujetos sin síntomas cardiovasculares.MétodosSe ha analizado el perfil metabólico, el espesor íntima-media carotídeo (EIMc), marcadores inflamatorios (fibrinógeno, proteína C reactiva, interleucina 6) y de daño endotelial (factor de von Willebrand), así como la concentración de MMP (1, 9 y 10) y su inhibidor (TIMP-1), en 400 sujetos asintomáticos con factores de riesgo cardiovascular, divididos en no fumadores (n = 195), fumadores (n = 118) y ex fumadores (n = 87). Asimismo se determinó el riesgo vascular total (PROCAM y REGICOR).ResultadosEl grupo de fumadores presentaba un aumento significativo de MMP-1 (p < 0,05) y MMP-10 (p < 0,001) respecto a los no fumadores, sin diferencias en MMP-9, TIMP-1, EIMc u otros parámetros inflamatorios. Las concentraciones de MMP-10 se correlacionaron con los índices PROCAM y REGICOR (p < 0,001). La asociación entre tabaquismo y MMP-10 se mantuvo en el análisis multivariable tras ajustar por edad, sexo y factores de riesgo cardiovascular (p < 0,01). En análisis de regresión múltiple, el tabaquismo contribuyó al 28% de la variabilidad en las cifras de MMP-10.ConclusionesLa MMP-10 se asoció de forma independiente con el tabaquismo en sujetos asintomáticos. La relación entre MMP-10 y MEC podría indicar un papel de esa MMP en el proceso aterosclerótico asociado al tabaquismo.