Publish in this journal
Journal Information
Vol. 61. Issue 12.
Pages 1267-1273 (December 2008)
Download PDF
More article options
Vol. 61. Issue 12.
Pages 1267-1273 (December 2008)
DOI: 10.1016/S1885-5857(09)60054-2
Full text access
Association Between Matrix Metalloproteinase-10 Concentration and Smoking in Individuals Without Cardiovascular Disease
Asociación de la metaloproteinasa-10 y el tabaquismo en sujetos sin enfermedad cardiovascular
José A Páramoa, Oscar Beloquib, José A Rodrígueza, Javier Dieza, Josune Orbea
a División of Cardiovascular Sciencies, Center for Applied Medical Research,University of Navarra, Pamplona, Navarra, Spain
b Department of Internal Medicine, University Hospital, University of Navarra, Pamplona, Navarra, Spain
This item has received
Article information
Tables (4)
TABLE 1. Clinical Characteristics and Cardiovascular Risk Factors in the Overall Study Population and by Sex
TABLE 2. Differences in Cardiovascular Risk Factors, Inflammatory and Proteolytic Markers Between Smokers and Never Smokers
TABLE 3. Correlation (Pearson's r) of MMP-1 and MMP-10 With Risk Factors and Inflammatory and Proteolytic Markers in Smokers and Non-Smokers (n=313)
TABLE 4. Multiple Regression Analysis (MMP-10 as Dependent Variable)
Show moreShow less
Figures (1)
Introduction and objectives. Smoking 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. Methods. Metabolic parameters, the carotid intima-media thickness (IMT), inflammatory markers (fibrinogen, C-reactive protein and interleukin-6), markers of endothelial damage (e.g., 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. Results. Both 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. Conclusions. There 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.
Cardiovascular risk
Introducción y objetivos. El 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. Métodos. Se 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). Resultados. El 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. Conclusiones. La 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.
Palabras clave:
Riesgo cardiovascular
Full Text


Smoking causes 11% of all mortality cardiovascular,1 while recent studies in Spain indicate that the incidence of cardiovascular disease attributable to smoking in men is approximately 40%.2 Tobacco consumption independently increases the risk of coronary, cerebral, and peripheral atherosclerotic disease,3 both in active and passive smokers.4 However, the pathogenesis of cardiovascular disease associated with smoking is not completely understood, though it has been linked with endothelial dysfunction, alterations in the balance between coagulation and fibrinolysis, and metabolic lipid changes,5,6 areas in which vascular inflammation and oxidative stress would play a central role.7

Recent studies indicate that an alteration in the balance between synthesis and degradation of the extracellular matrix (ECM) could also contribute to the development of cardiovascular disease associated with smoking.8 The metalloproteinases (MMP), a family of endopeptidases that break down various components of the ECM, are classified into subgroups based on their structure, substrate specificity, and membrane binding properties: collagenase (MMP-1, MMP-8, MMP-13), stromelysin (MMP-3, MMP-10, MMP-11), gelatinase (MMP-2, MMP-9), membrane type (MTMMP), and others (matrilysin, metaloelastase, etc). Intra- and extracellular MMP activity is regulated through transcription, postranslation, and through interaction with specific inhibitors (TIMP).9

The MMPs have been implicated in the inflammatory, angiogenic, and proteolytic processes that accompany angiogenic remodeling and the break-up or erosion of vulnerable plaque which is also associated with smoking.8 An increase in the number of MMPs has also been linked to cardiovascular disease, which has led to calls for them to be used as a biomarkers.9-11 Their importance in the development of chronic obstructive pulmonary disease (COPD), the second leading cause of death associated with smoking, is also well-known.12,13

Recent studies by our group have shown a strong link between inflammation, subclinical atherosclerosis, and increases in circulating MMP-10 (stromelysin 2),14,15 an MMP that breaks down type III and IV collagen, elastin, and proteoglucanes, and which is also present at increased levels in atherosclerotic plaques in patients with advanced atherosclerosis.14

The objective of this study was to determine whether MMP-10 was associated with smoking in asymptomatic subjects, independently of other risk factors. If that was the case, it could be relevant to the atherogenic process through its effects on ECM. To answer the study question, we quantified the levels of several circulating MMPs and TIMP-1 in both smokers and non-smokers without cardiovascular disease.


We analyzed a group of 400 apparently healthy subjects (mean age [range], 54.3 [20-80] years). Subjects were predominantly male and have been described previously.15 Samples were taken sequentially during the period 2003-2005 when subjects attended the outpatient service of the Department of Internal Medicine at the University Clinic of Navarra for a general checkup. Subjects were selected by the attending physician from a population of 414 subjects without evidence of symptomatic cardiovascular disease according to the following criteria: a) no history of heart disease, stroke, or peripheral arterial disease; and b) normal electrocardiogram and chest x-ray. Coronary artery disease was defined as: a) a history of acute myocardial infarction (AMI), angina, or use of nitroglycerine; and b) a history of coronary angioplasty or bypass surgery. Cerebrovascular disease was defined as a history of stroke, transient ischemic attack, or carotid endarterectomy. Any symptoms of intermittent claudication were recorded and an exploration was performed to evaluate the peripheral pulses. Other exclusion criteria were: substantial alteration of renal function (glomerular filtration <60 mL/min), presence of chronic inflammatory disease, and administration of anti-inflammatory medication, antithrombotic or hormone therapy in the 2 previous weeks. Subjects with acute infection based on clinical criteria were also excluded.

Assessment of Smoking and Other Cardiovascular Risk Factors

We used a standardized questionnaire on tobacco consumption to classify subjects as smokers (at least 1 cigarette daily on average over the past year), never smokers, and former smokers (no cigarette consumption in the past year).

In addition, we obtained information about other atherosclerotic risk factors, including diabetes mellitus, high blood pressure, dyslipidemia, and obesity. Subjects were considered hypertensive if they had a systolic blood pressure (SBP) >139 mm Hg and / or diastolic blood pressure (DBP) >89 mm Hg, and / or if they were taking antihypertensive drugs. Dyslipidemia was diagnosed when total cholesterol values were ≥200 mg/dL, LDL cholesterol (LDL-C) was ≥130 mg/dL, HDL cholesterol (HDL-C) was ≤50 mg/dL, triglycerides were ≥150 mg/dL and / or if the subject was taking lipid-lowering medication. Subjects were classified as obese if they had a body mass index (BMI) of ≥30 and diabetes mellitus was considered present when glucose values were > 126 mg/dL or if the subject was taking anti-diabetic medication.

We calculated total vascular risk using the REGICOR charts,16 which have been validated in the Spanish population, and PROCAM,17 which was validated in the German population.

Informed consent was obtained from all subjects and the study was approved by the Institutional Review Board in accordance with the Declaration of Helsinki (October 2000 revision).


Fasting plasma and serum samples were extracted between 8:00 am and 10:00 am by venipuncture. They were centrifuged (20 min, 1200 g) and frozen at -80° C until analysis.

Metabolic Profile

We measured total cholesterol, HDL-C, triglycerides, and glucose using standard laboratory techniques in fasting blood samples. Levels of LDL-C were calculated using the Friedwald equation.

Inflammatory Markers

Plasma fibrinogen activity was measured using Clauss' method. Concentrations of high sensitivy-C-reactive protein (hs-CRP) (IMMULITE Diagnostic Product Corporation, USA), interleukin (IL) 6 (Quantikine R & D Systems, UK ) and von Willebrand factor (VWF) (Asserachrom Diagnostica Stago, France) were determined using ELISA following the manufacturer's instructions. Inter- and intra-analysis coefficients of variation for ELISA were under 6%.

Proteolytic Markers

Plasma concentrations of MMP-1, MMP-9, and TIMP-1, and serum concentrations of MMP-10 were estimated using ELISA (R & D systems, USA) following the manufacturer's instructions. Inter- and intra-analysis coefficients of variation for ELISA were under 6%.

Determining Carotid Intima Media Thickness (IMT)

Carotid intima media thickness (IMT) was measured in all subjects by Doppler ultrasound of the common carotid arteries (CCA), as described previously.15 A 5-12 MHz linear transducer (ATL HDI 5000) was used. The IMT was measured in regions without plaque 1 cm from the carotid bulb in each CCA. Two echocardiograph technicians who were unaware of the clinical history determined mean readings for each CCA.

Statistical Analysis

Quantitative variables are expressed as mean (standard deviation). The Kolmogorov-Smirnov test was used to test the normality of the distributions. Log transformations were used to normalize hs-CRP values for further statistical analysis. Differences in mean values and proportions in relation to sex and smoking were analyzed using Student t test and c2, respectively. Former smokers were excluded from the analysis.

Pearson's correlation coefficient was used to analyze correlations between concentrations of inflammatory and proteolytic markers, and cardiovascular risk factors. We calculated the marginal means for smokers and non-smokers using analysis of variance (ANCOVA), after adjusting for age, sex, and cardiovascular risk factors. A multivariable linear regression analysis was used to determine whether the association between MMP-10 and smoking was independent of these risk factors and to estimate the relative importance of each variable. All variables were entered using stepwise procedures. The statistical analysis was performed with SPSS 11.0. A P value less than .05 was considered significant.


A non-randomized sample of 400 subjects without clinical cardiovascular disease was included (mean [interval] age, 54.3 [20-80] years; 78% male). There were high proportions of subjects with dyslipidemia (81%), high blood pressure (50.7%), and obesity (32%), and a lower prevalence of subjects with diabetes (16%). The study population's clinical characteristics and cardiovascular risk factors are shown in Table 1 for the overall sample and by gender. Male subjects (n=311) were younger (P<.05), with a higher proportion of smokers and former smokers (P<.01). They also had significantly lower levels of HDL-C and higher triglyceride and glucose values (P<.01) than female subjects (n=89). Total vascular risk on the REGICOR chart (P<.01) and IMT values (P<.01) were higher in men.

Table 2 shows the differences in cardiovascular risk factors, inflammatory and proteolytic markers among the group of active smokers (n=118) and never-smokers (n=195). Smokers were younger and predominantly male (P<.001). While no difference was seen between groups in the prevalence of other cardiovascular risk factors or fibrinogen levels, PCR-us, VWF, IL-6, MMP-9, or TIMP-1, MMP-1 (P<0.05), and MMP-10 values were significantly higher (P<.001) in smokers. No significant differences were seen for IMT.

The results of analyzing correlations for both MMPs are shown in Table 3. MMP-1 was correlated with LDL-C (P<.01), total cholesterol, and TIMP-1 (P<.05), whereas MMP-10 showed a significant correlation with age (P<.05), HDL-C (P<.05), fibrinogen (P<.01), IMT (P<.05), and TIMP-1 (P<.01), as well as with PROCAM and REGICOR scores (P<.01). After adjusting for age, sex, and cardiovascular risk factors which were significant in the univariate analysis, only MMP-10 was still statistically significantly higher (P<.001) in smokers (Figure 1). Finally, a multiple regression analysis, in which standardized regression coefficients were defined, was performed to assess the relative importance of each of the variables which were independently associated with MMP-10 concentrations. As shown in Table 4, the variables that contributed significantly to the variations in MMP levels were age (15%, P<.01) and, to a greater extent, smoking (28%, P<.001).

Figure 1. Concentrations of MMP-10 in smokers and non-smokers without cardiovascular disease. Analysis of covariance (ANCOVA) adjusted for cardiovascular risk factors which were significant in the univariate analysis


In a series of subjects without cardiovascular symptoms, concentrations of circulating MMP-10 (stromelysin 2) were significantly higher in smokers compared to non-smokers. The association between MMP-10 and smoking was independent of other, traditional risk factors. In fact, smoking made the greatest contribution in explaining variability in levels of MMP-10. These results suggest that high levels of MMP-10 may be an additional cardiovascular risk factor associated with smoking in subjects without symptomatic cardiovascular disease. Of added interest is the fact that this molecule mediates the degradation of ECM, the erosion and breakdown of which are related to atherothrombotic syndromes.8,9 A correlation between MMP-10 and total cardiovascular risk, estimated using the PROCAM and REGICOR scores, was also observed. Nevertheless, the correlation was weak making its clinical significance uncertain. Finally, MMP-10 correlated with IMT, a marker of subclinical atherosclerosis.15 In the multivariate analysis, age (15%) and smoking (28%) made the greatest contribution to high levels of circulating MMP-10.

We also found a correlation between MMP-1 (collagenase 1) and smoking, which confirmed previous survey data.18-21 No correlation with other MMPs or TIMP-1 was observed. Overall, the results of this study suggest that an alteration in the balance between synthesis and degradation of ECM can, by increasing the concentrations of several MMPs, play an important part in the genesis of cardiovascular changes associated with tobacco consumption in subjects asymptomatic for cardiovascular disease.8

Smoking is an independent risk factor for coronary, cerebrovascular, and peripheral atherosclerosis, as well as for aortic aneurysms.22,23 The simultaneous occurrence of factors, such as cholesterol or high blood pressure, does not adequately explain the increased cardiovascular risk associated with smoking.24,25 However, a synergy between various MMPs and smoking in relation to cardiovascular disease has been observed.26,27 An excessive inflammatory and oxidative response, mediated by cytokines and NF-kB or AP-1 type transcription factors, appears to be important in the over-expression of MMPs in smokers.8,28-32 It is also possible, given the close relationship between smoking and COPD, that the higher levels of MMP-10 originate in the lungs.13

In our study, MMP-10 was found to have a particularly strong association with tobacco consumption. MMP-10 is released by the endothelium in response to inflammatory stimuli, which can be significantly involved in vascular remodeling and the appearance of atherothrombotic complications.9,33 Recent studies by our group have shown higher levels in asymptomatic subjects with cardiovascular risk factors and subclinical atherosclerosis,15 as well as in patients with established atherosclerotic disease.14 Interestingly, MMP-10 has also been associated with aortic aneurysms.34 The results of this study emphasize the importance of this MMP in smokers, whereas other markers of inflammation and endothelial damage such as fibrinogen, IL-6, and VWF associated with subclinical atherosclerosis in asymptomatic subjects,35,36 appear to be less useful in assessing smoking-related cardiovascular risk. While MMP-10 was correlated with age in the study population, it is interesting to note that MMP-10 levels were elevated in smokers, who were generally younger. These results were confirmed in multivariate analysis after adjusting for this variable.

Various mechanisms have been proposed to explain the induction of MMP through smoking, both in vitro and in vivo.6,37,38 The exposure of endothelial cells in vitro to tobacco smoke induces the expression of MMP-1, MMP-8, and MMP-919,32; in a similar fashion, tobacco smoke stimulates the production of MMP-1 through human fibroblasts.21 While increased levels of cadmium inhaled with tobacco smoke could induce proteinolysis, as demonstrated in COPD,13 they could also contribute to cardiovascular disease, as suggested by increased levels in the aorta of smokers39 and in patients with peripheral arterial disease.40

Unlike other studies in patients with clinical cardiovascular disease,26,27,29,38 we did not find any differences between smokers and non-smokers in terms of other MMPs, such as MMP-9 or TIMP-1; this may be related to the type of sample analyzed and the exclusion of patients with clinical atherosclerosis.

The study has several limitations. The cross-sectional design means it is not possible to establish causal associations between proteolytic marker values and cardiovascular risk; prospective studies are required for that. The low number of women included and the fact that the sample was not randomized means the results can not be extrapolated to the general population. Finally, some MMP values are subject to circadian variations that cannot be detected in a cross-sectional sample, although all extractions were performed in the same time period.41


The group of asymptomatic smokers studied here showed an increase in MMP-10 that was independent of other traditional atherosclerotic risk factors. The close relationship between tobacco consumption and MMP-10 and between the latter and the regulation of EMC could indicate that this MMP plays a key role in the atherosclerotic process associated with smoking.

IMT: carotid intima media thickness
ECM: extracellular matrix
IL-6: interleukin 6
MMP: metalloproteinase
MT-MMP: membrane type metalloproteinase TIMP: tissue inhibitor of metalloproteinases

Financed by UTE project CIMA (Universidad de Navarra, Pamplona, Navarra, Spain) and Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III (RECAVA RD06/0014/0008).

Correspondence: Dr. J.A. Páramo.
Laboratorio de Aterosclerosis. Área de Ciencias Cardiovasculares, CIMA. Avda. Pío XII, 55. 31008 Pamplona. Navarra. España.

Received February 20, 2008.
Accepted for publication August 29, 2008.

Ezzati M, Lopez AD..
Estimates of global mortality attributable to smoking in 2000..
Medrano MJ, Pastor-Barriuso R, Boix R, del Barrio JL, Damián J, Alvarez R, et al..
Riesgo coronario atribuible a los factores de riesgo cardiovascular en población española..
Rev Esp Cardiol, 60 (2007), pp. 1250-6
Willigendael EM, Teijink JA, Bartelink ML, Kuiken BW, Boiten J, Moll FL, et al..
Influence of smoking on incidence and prevalence of peripheral arterial disease..
J Vasc Surg, 40 (2004), pp. 1158-65
Law MR, Morris JK, Wald NJ..
Environmental tobacco smoke exposure and ischaemic heart disease: an evaluation of the evidence..
BMJ, 315 (1997), pp. 973-80
Ambrose JA, Barua RS..
The pathophysiology of cigarette smoking and cardiovascular disease: an update..
J Am Coll Cardiol, 43 (2004), pp. 1731-7
MacCallum PK..
Markers of hemostasis and systemic inflammation in heart disease and atherosclerosis in smokers..
Proc Am Thorac Soc, 2 (2005), pp. 34-43
Wang Z, Nicholls SJ, Rodriguez ER, Kummu O, Horkko S, Barnard J, et al..
Protein carbamylation links inflammation, smoking, uremia and atherogenesis..
Nat Med, 13 (2007), pp. 1176-84
Perlstein TS, Lee RT..
Smoking, metalloproteinases, and vascular disease..
Arterioscler Thromb Vasc Biol, 26 (2006), pp. 250-6
Rodriguez JA, Orbe J, Paramo JA..
Metaloproteasas, remodelado vascular y síndromes aterotrombóticos..
Rev Esp Cardiol, 60 (2007), pp. 959-67
Tuomainen AM, Nyyssonen K, Laukkanen JA, Tervahartiala T, Tuomainen TP, Salonen JT, et al..
Serum matrix metalloproteinase-8 concentrations are associated with cardiovascular outcome in men..
Arterioscler Thromb Vasc Biol, 27 (2007), pp. 2722-8
Pinon P, Kaski JC..
Inflamación, aterosclerosis y riesgo cardiovascular: PAPP-A, Lp-PLA2 y cistatina C..
??Nuevas aportaciones o informaci??n redundante? Rev Esp Cardiol, 59 (2006), pp. 247-58
Shapiro SD, Ingenito EP..
The pathogenesis of chronic obstructive pulmonary disease: advances in the past 100 years..
Am J Respir Cell Mol Biol, 32 (2005), pp. 367-72
Srivastava PK, Dastidar SG, Ray A..
Chronic obstructive pulmonary disease: role of matrix metalloproteases and future challenges of drug therapy..
Expert Opin Investig Drugs, 16 (2007), pp. 1069-78
Montero I, Orbe J, Varo N, Beloqui O, Monreal JI, Rodriguez JA, et al..
C-reactive protein induces matrix metalloproteinase-1 and -10 in human endothelial cells: implications for clinical and subclinical atherosclerosis..
J Am Coll Cardiol, 47 (2006), pp. 1369-78
Orbe J, Montero I, Rodriguez JA, Beloqui O, Roncal C, Paramo JA..
Independent association of matrix metalloproteinase-10, cardiovascular risk factors and subclinical atherosclerosis..
J Thromb Haemost, 5 (2007), pp. 91-7
Ramos R, Solanas P, Cordon F, Rohlfs I, Elosua R, Sala J, et al..
Comparación de la función Framingham original y la calibrada del REGICOR en la predicción del riesgo coronario poblacional..
Med Clin (Barc), 121 (2003), pp. 521-6
Assmann G, Cullen P, Schulte H..
Simple scoring scheme for calculating the risk of acute coronary events based on the 10-year follow-up of the prospective cardiovascular Munster (PROCAM) study..
Circulation, 105 (2002), pp. 310-5
Lahmann C, Bergemann J, Harrison G, Young AR..
Matrix metalloproteinase-1 and skin ageing in smokers..
Nordskog BK, Blixt AD, Morgan WT, Fields WR, Hellmann GM..
Matrix-degrading and pro-inflammatory changes in human vascular endothelial cells exposed to cigarette smoke condensate..
Cardiovasc Toxicol, 3 (2003), pp. 101-17
Nordskog BK, Blixt AD, Zieske AW, Hellmann GM..
MMP-1 polymorphic expression in aortic endothelial cells: possible role in lesion development in smokers and nonsmokers..
Cardiovasc Toxicol, 4 (2004), pp. 75-83
Kim H, Liu X, Kohyama T, Kobayashi T, Conner H, Abe S, et al..
Cigarette smoke stimulates MMP-1 production by human lung fibroblasts through the ERK1/2 pathway..
Himbert D, Klutman M, Steg G, White K, Gulba DC..
Cigarette smoking and acute coronary syndromes: a multinational observational study..
Int J Cardiol, 100 (2005), pp. 109-17
Wong DR, Willett WC, Rimm EB..
Smoking, hypertension, alcohol consumption, and risk of abdominal aortic aneurysm in men..
Am J Epidemiol, 165 (2007), pp. 838-45
Khot UN, Khot MB, Bajzer CT, Sapp SK, Ohman EM, Brener SJ, et al..
Prevalence of conventional risk factors in patients with coronary heart disease..
JAMA, 290 (2003), pp. 898-904
Yusuf S, Hawken S, Ounpuu S, Dans T, Avezum A, Lanas F, et al..
Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study..
Liu PY, Chen JH, Li YH, Wu HL, Shi GY..
Synergistic effect of stromelysin-1 (matrix metallo-proteinase-3) promoter 5A/6A polymorphism with smoking on the onset of young acute myocardial infarction..
Thromb Haemost, 90 (2003), pp. 132-9
Liu PY, Li YH, Chan SH, Lin LJ, Wu HL, Shi GY, et al..
Genotype-phenotype association of matrix metalloproteinase-3 polymorphism and its synergistic effect with smoking on the occurrence of acute coronary syndrome..
Am J Cardiol, 98 (2006), pp. 1012-7
Mochida-Nishimura K, Surewicz K, Cross JV, Hejal R, Templeton D, Rich EA, et al..
Differential activation of MAP kinase signaling pathways and nuclear factor-kappaB in bronchoalveolar cells of smokers and nonsmokers..
Mol Med, 7 (2001), pp. 177-85
Kangavari S, Matetzky S, Shah PK, Yano J, Chyu KY, Fishbein MC, et al..
Smoking increases inflammation and metalloproteinase expression in human carotid atherosclerotic plaques..
J Cardiovasc Pharmacol Ther, 9 (2004), pp. 291-8
Harding SA, Sarma J, Josephs DH, Cruden NL, Din JN, Twomey PJ, et al..
Upregulation of the CD40/CD40 ligand dyad and platelet-monocyte aggregation in cigarette smokers..
Walters MJ, Paul-Clark MJ, McMaster SK, Ito K, Adcock IM, Mitchell JA..
Cigarette smoke activates human monocytes by an oxidant-AP-1 signaling pathway: implications for steroid resistance..
Mol Pharmacol, 68 (2005), pp. 1343-53
Wright JL, Tai H, Wang R, Wang X, Churg A..
Cigarette smoke upregulates pulmonary vascular matrix metalloproteinases via TNF-alpha signaling..
Am J Physiol Lung Cell Mol Physiol, 292 (2007), pp. L125-33
Rodriguez JA, Orbe J, Martinez de Lizarrondo S, Calvayrac O, Rodriguez C, Martinez-Gonzalez J, et al..
Metalloproteinases and atherothrombosis: MMP-10 mediates vascular remodeling promoted by inflammatory stimuli..
Front Biosci, 13 (2008), pp. 2916-21
Ogata T, Shibamura H, Tromp G, Sinha M, Goddard KA, Sakalihasan N, et al..
Genetic analysis of polymorphisms in biologically relevant candidate genes in patients with abdominal aortic aneurysms..
J Vasc Surg, 41 (2005), pp. 1036-42
Paramo JA, Beloqui O, Roncal C, Benito A, Orbe J..
Validation of plasma fibrinogen as a marker of carotid atherosclerosis in subjects free of clinical cardiovascular disease..
Haematologica, 89 (2004), pp. 1226-31
Paramo JA, Beloqui O, Colina I, Diez J, Orbe J..
Independent association of von Willebrand factor with surrogate markers of atherosclerosis in middle-aged asymptomatic subjects..
J Thromb Haemost, 3 (2005), pp. 662-4
Expression of matrix metalloproteinases, tissue inhibitors of metalloproteinases, and extracellular matrix mRNA following exposure to mineral fibers and cigarette smoke in vivo. Environ Health Perspect. 1997;105 Suppl 5:1247-51.
Nakamura T, Ebihara I, Shimada N, Koide H..
Effect of cigarette smoking on plasma metalloproteinase-9 concentration..
Clin Chim Acta, 276 (1998), pp. 173-7
Abu-Hayyeh S, Sian M, Jones KG, Manuel A, Powell JT..
Cadmium accumulation in aortas of smokers..
Arterioscler Thromb Vasc Biol, 21 (2001), pp. 863-7
Navas-Acien A, Selvin E, Sharrett AR, Calderon-Aranda E, Silbergeld E, Guallar E..
Lead, cadmium, smoking, and increased risk of peripheral arterial disease..
Circulation, 109 (2004), pp. 3196-201
Dominguez-Rodriguez A, Abreu-Gonzalez P, Garcia-Gonzalez MJ, Reiter RJ..
Relation of nocturnal melatonin levels to serum matrix metalloproteinase-9 concentrations in patients with myocardial infarction..
Thromb Res, 120 (2007), pp. 361-6
Revista Española de Cardiología (English Edition)

Subscribe to our newsletter

Article options
es en

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?

es en
Política de cookies Cookies policy
Utilizamos cookies propias y de terceros para mejorar nuestros servicios y mostrarle publicidad relacionada con sus preferencias mediante el análisis de sus hábitos de navegación. Si continua navegando, consideramos que acepta su uso. Puede cambiar la configuración u obtener más información aquí. To improve our services and products, we use "cookies" (own or third parties authorized) to show advertising related to client preferences through the analyses of navigation customer behavior. Continuing navigation will be considered as acceptance of this use. You can change the settings or obtain more information by clicking here.