The C242T polymorphism of the p22-phox gene (CYBA) is associated with higher left ventricular mass in Brazilian hypertensive patients

<p>Abstract</p> <p>Background</p> <p>Reactive oxygen species have been implicated in the physiopathogenesis of hypertensive end-organ damage. This study investigated the impact of the C242T polymorphism of the p22-phox gene (CYBA) on left ventricular structure in Brazilian hypertensive subjects.</p> <p>Methods</p> <p>We cross-sectionally evaluated 561 patients from 2 independent centers [Campinas (n = 441) and Vitória (n = 120)] by clinical history, physical examination, anthropometry, analysis of metabolic and echocardiography parameters as well as p22-phox C242T polymorphism genotyping. In addition, NADPH-oxidase activity was quantified in peripheral mononuclear cells from a subgroup of Campinas sample.</p> <p>Results</p> <p>Genotype frequencies in both samples were consistent with the Hardy- Weinberg equilibrium. Subjects with the T allele presented higher left ventricular mass/height^2.7than those carrying the CC genotype in Campinas (76.8 ± 1.6 vs 70.9 ± 1.4 g/m^2.7; p = 0.009), and in Vitória (45.6 ± 1.9 vs 39.9 ± 1.4 g/m^2.7; p = 0.023) samples. These results were confirmed by stepwise regression analyses adjusted for age, gender, blood pressure, metabolic variables and use of anti-hypertensive medications. In addition, increased NADPH-oxidase activity was detected in peripheral mononuclear cells from T allele carriers compared with CC genotype carriers (p = 0.03).</p> <p>Conclusions</p> <p>The T allele of the p22-phox C242T polymorphism is associated with higher left ventricular mass/height^2.7and increased NADPH-oxidase activity in Brazilian hypertensive patients. These data suggest that genetic variation within NADPH-oxidase components may modulate left ventricular remodeling in subjects with systemic hypertension.</p

Development And Reliability Of An Instrument To Measure Psychosocial Determinants Of Salt Consumption Among Hypertensive Patients [desarrollo Y Confiabilidad De Un Instrumento Para Medir Los Factores Psicosociales Determinantes En El Consumo De Sal Entre Hipertensos]

This study aimed to present the content validity and reliability analyses of an instrument to study the determinant factors of salt consumption among hypertensive subjects, based on an extension of the Theory of Planned Behavior. Content validity was assessed by 3 experts and a pre-test was carried out with 5 subjects. The final tool, comprising 3 different behaviors related to salt consumption and corresponding psychosocial variables, was applied to 32 subjects for internal consistency and temporal stability (15-day interval) analysis. Cronbach's alpha coefficients > 0.70 and significant intra-class correlation coefficients were observed for most variables, indicating the temporal stability of the measured concepts. The developed instrument exhibited evidence of both content validity and reliability.175701707Roberts, W.C., High salt intake, its origins, its economic impact, and its effect on blood pressure (2001) Am J Cardiol, 88, pp. 1338-46Ajani, U.A., Dunbar, S.B., Ford, E.S., Mokdad, A.H., Mensah, G.A., Sodium intake among people with normal and high blood pressure (2005) Am J Prev Med, 29 (5 S1), pp. 63-7Ferreira, M.C.S., (2007) Consumo E Sensibilidade Ao Sódio: Caracterização Genética E Do Comportamento Em Saúde De Pacientes Hipertensos [dissertação], , Campinas (SP): Universidade Estadual de CampinasBlackburn, G.L., Waltman, B.A., Physician's guide to the new 2005 dietary guidelines (2005) How Best to Counsel Patients. Clev Clin J Med, 72 (7), pp. 609-18du Cailar, G., Ribstein, J., Mimran, A., Dietary sodium and target organ damagem in essential hypertension (2002) Am J Hypert, 15, pp. 222-9Sacks, F.M., Svetkey, L.P., Vollmer, W.M., Appel, L.J., Bray, G.A., Harsha, D., The sodium-restricted DASH diet lowers blood pressure (2001) Cmaj, 164 (11), p. 1613Pessuto, J., Carvalho, E.C., Fatores de risco em indivíduos com hipertensão arterial (1998) Rev Latino-am Enfermagem, 6 (1), pp. 33-9Simonetti, J.P., Batista, L., Carvalho, L.R., Hábitos de saúde e fatores de risco em pacientes hipertensos (2002) Rev Latino-am Enfermagem, 10 (3), pp. 415-22Godin, G., L'éducation pour la santé: Les fondements psychosociaux de la définition des messages éducatifs (1991) Sciences Sociales Et Santé, 9 (1), pp. 67-94Conner, M., Norman, P., Predicting health behaviour: A social cognition approach (2005) Predicting Health Behaviour, pp. 1-9. , In: Conner M, Norman P., 2a ed. London: Open University PressAjzen, I., (2002) Constructing a Tpb Questionnaire: Conceptual and Methodological Considerations, , http://people.umass.edu/aizen, [on-line], sep, revisado em jan 2006. [acesso em fev 2008]. Disponível emArmitage, C., Evidence that implementation intentions reduce dietary fat intake: A randomized trial (2004) Health Psychol, 23 (3), pp. 319-23Godin, G., Kok, K., The Theory of Planned Behavior: A review of its applications to health-related behaviors (1996) American Journal Health Promotion, 11 (2), pp. 87-98Padilha, K.M., Gallani, M.C.B.J., Colombo, R.C.R., Development of an instrument to measure beliefs and attitudes from heart valve disease patients (2004) Rev Latino-am Enfermagem, 12 (3), pp. 453-9Guillemin, F., Bombardier, C., Beaton, D., Cross-cultural adaptation of health related quality of life measures: Literature review and proposed guidelines (1993) J Clin Epidem, 46, pp. 1417-32Fishbien, M., Ajzen, I., (1980) Understanding Attitudes and Predicting Social Behavior, , London: Prentice HallNunnally, J.C., (1978) Psychometric Theory, , New York: McGraw-HillVan der Veen, J.E., de Graaf, C., van Dis, S.J., van Staveren, W.A., Determinants of salt use in cooked meals in the Netherlands: Attitudes and practices of food preparers (1999) Eur J Clin Nut, 53, pp. 388-94Blue, C.L., Marrero, D.G., Psychometric properties of the healthful eating belief scales for persons at risk of Diabetes (2006) J Nutr Educ Behav, 38, pp. 134-4

Adverse interaction between HDL and the mass of myocardial infarction

Coronary reperfusion with HDL from healthy volunteers attenuates ischemia and reperfusion injury in animal models. In myocardial infarction (MI) patients, such an interaction is unclear. Hence, our first objective was to verify if there is interaction between HDL-C and MI mass in patients and the role of coronary reperfusion in the interaction. Furthermore, we investigated whether the effect in MI size of reperfusion with HDL obtained from healthy participants or MI patients could differ. HDL-C was measured the first day after MI and MI mass was quantified by cardiac magnetic resonance (n = 94) and peak CKMB (n = 393). In an ex vivo rat heart model, we compared MI area and dP/dt max after coronary reperfusion with HDL from MI patients or healthy volunteers. HDL-C above the median (35 mg/dL) was associated with higher peak CKMB [255 (145–415) vs. 136 (84–287) UI/L; p = 0.02], higher MI mass [17 (9–21) vs. 10 (6–14) g; p < 0.01] and lower left ventricular ejection fraction [47 (34–53) vs. 51 (43–59); p = 0.02] than their counterparts. In restricted cubic spline and multivariate linear regression, HDL-C was directly associated with peak CKMB (p < 0.01) and MI mass (p < 0.01) only in reperfused patients with time to reperfusion <4 h. Reperfusion with healthy HDL, but not from MI patients, reduced MI mass (p < 0.01) and improved dP/dt max (p = 0.02). In MI patients undergoing early coronary reperfusion, HDL-C levels at admission are directly associated with MI size. In contrast to healthy HDL, reperfusion with HDL from MI patients do not reduce MI area in an ex vivo animal model.281916The Brasilia Heart Study group is coordinated by Prof. Sposito and the authors of this manuscript are among those responsible for the presented data. We thank the Brasilia Heart Study participants as well as the other investigators of the study for their contributio

Common matrix metalloproteinase 2 gene haplotypes may modulate left ventricular remodelling in hypertensive patients

Matrix metalloproteinases (MMPs) are involved in cardiac remodelling. We examined whether MMP-2 genetic polymorphisms are associated with hypertension and left ventricular (LV) remodelling in hypertensive patients. We studied 160 hypertensive patients and 123 healthy controls. Echocardiography was performed in all patients and the C-1306T (rs243865) and C-735T (rs 2285053) MMP-2 polymorphisms were analysed. Haplo.stats analysis was used to evaluate whether MMP-2 haplotypes are associated with hypertension and with extremes in LV mass index (LVMI). Multiple linear regression analysis was performed to assess whether MMP-2 genotypes or haplotypes affect LVMI and other echocardiography parameters. The C-1306T 'CC' genotype was associated with reduced LVMI and LV end-diastolic diameter (EDD) (P=0.0365 and P=0.0438, respectively). The haplotype 'C, C' was associated with reduced LVMI and EDD (P=0.0278 and P=0.0322, respectively). The comparison of upper and lower extremes of the LVMI phenotype showed that the 'C, C' haplotype was more common in the lower LVMI group (P=0.0060), whereas the 'T, C' haplotype was more common in the higher quartile of LVMI (P=0.0187), and this haplotype was associated with increased risk of higher LVMI values (odds ratio=3.5121, 95% confidence interval 1.3193-9.3494). The findings suggest that MMP-2 polymorphisms affect hypertension-induced LV remodellin263171177CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPES

Elevated Cetp Activity During Acute Phase Of Myocardial Infarction Is Independently Associated With Endothelial Dysfunction And Adverse Clinical Outcome

Objective: Recent data suggests that cholesteryl ester transfer protein (CETP) activity may interact with acute stress conditions via inflammatory-oxidative response and thrombogenesis. We investigated this assumption in patients with ST-elevation myocardial infarction (STEMI). Methods: Consecutive patients with STEMI (n=116) were enrolled &lt;24-hof symptoms onset and were followed for 180 days. Plasma levels of C-reactive protein (CRP), interleukin-2 (IL-2), tumor necrosis factor (TNFα), 8-isoprostane, nitric oxide (NOx) and CETP activity were measured at enrollment (D1) and at fifth day (D5). Flow-mediated dilation (FMD) was assessed by ultrasound and coronary thrombus burden (CTB) was evaluated by angiography. Results: Neither baseline nor the change of CETP activity from D1 to D5 was associated with CRP, IL-2, TNFα, 8-isoprostane levels or CTB. The rise in NOx from D1 to D5 was inferior [3.5(-1; 10) vs. 5.5(-1; 12); p&lt;0.001] and FMD was lower [5.9(5.5) vs. 9.6(6.6); p=0.047] in patients with baseline CETP activity above the median value than in their counterparts. Oxidized HDL was measured by thiobarbituric acid reactive substances (TBARS) in isolated HDL particles and increased from D1 to D5, and remaining elevated at D30. The change in TBARS content in HDL was associated with CETP activity (r=0.72; p=0.014) and FMD (r=-0.61; p=0.046). High CETP activity at admission was associated with the incidence of sudden death and recurrent MI at 30 days (OR 12.8; 95% CI 1.25-132; p=0.032) and 180 days (OR 3.3; 95% CI 1.03-10.7; p=0.044). Conclusions: An enhanced CETP activity during acute phase of STEMI is independently associated with endothelial dysfunction and adverse clinical outcome.2372777783Cazita, P.M., Barbeiro, D.F., Moretti, A.I., Quintao, E.C., Soriano, F.G., Human cholesteryl ester transfer protein expression enhances the mouse survival rate in an experimental systemic inflammation model: a novel role for CETP (2008) Shock, 30 (5), pp. 590-595Deguchi, H., Fernandez, J.A., Griffin, J.H., Plasma cholesteryl ester transfer protein and blood coagulability (2007) Thromb. Haemost., 98 (6), pp. 1160-1164Grion, C.M., Cardoso, L.T., Perazolo, T.F., Garcia, A.S., Barbosa, D.S., Morimoto, H.K., Lipoproteins and CETP levels as risk factors for severe sepsis in hospitalized patients (2010) Eur. J. Clin. Investig., 40 (4), pp. 330-338Frangogiannis, N.G., Smith, C.W., Entman, M.L., The inflammatory response in myocardial infarction (2002) Cardiovasc. Res., 53 (1), pp. 31-47Campo, G., Valgimigli, M., Ferraresi, P., Malagutti, P., Baroni, M., Arcozzi, C., Tissue factor and coagulation factor VII levels during acute myocardial infarction: association with genotype and adverse events (2006) Arterioscler. Thromb. Vasc. Biol., 26 (12), pp. 2800-2806Minnema, M.C., Peters, R.J., de Winter, R., Lubbers, Y.P., Barzegar, S., Bauer, K.A., Activation of clotting factors XI and IX in patients with acute myocardial infarction (2000) Arterioscler. Thromb. Vasc. Biol., 20 (11), pp. 2489-2493Sposito, A.C., Carvalho, L.S., Cintra, R.M., Araujo, A.L., Ono, A.H., Andrade, J.M., Rebound inflammatory response during the acute phase of myocardial infarction after simvastatin withdrawal (2009) Atherosclerosis, 207 (1), pp. 191-194Lagrost, L., Determination of the mass concentration and the activity of the plasma cholesteryl ester transfer protein (CETP) (1998) Methods Mol. Biol., 110, pp. 231-241Chapman, M.J., Goldstein, S., Lagrange, D., Laplaud, P.M., Adensity gradient ultracentrifugal procedure for the isolation of the major lipoprotein classes from human serum (1981) J.Lipid Res., 22 (2), pp. 339-358Ye, D., Kraaijeveld, A.O., Grauss, R.W., Willems, S.M., van Vark-van der Zee, L.C., de Jager, S.C., Reduced leucocyte cholesteryl ester transfer protein expression in acute coronary syndromes (2008) J.Intern. Med., 264 (6), pp. 571-585Jahangiri, A., de Beer, M.C., Noffsinger, V., Tannock, L.R., Ramaiah, C., Webb, N.R., HDL remodeling during the acute phase response (2009) Arterioscler. Thromb. Vasc. Biol., 29 (2), pp. 261-267Blaschke, F., Takata, Y., Caglayan, E., Collins, A., Tontonoz, P., Hsueh, W.A., Anuclear receptor corepressor-dependent pathway mediates suppression of cytokine-induced C-reactive protein gene expression by liver X receptor (2006) Circ. Res., 99 (12), pp. e88-99Fang, C., Yoon, S., Tindberg, N., Jarvelainen, H.A., Lindros, K.O., Ingelman-Sundberg, M., Hepatic expression of multiple acute phase proteins and down-regulation of nuclear receptors after acute endotoxin exposure (2004) Biochem. Pharmacol., 67 (7), pp. 1389-1397Luo, Y., Tall, A.R., Sterol upregulation of human CETP expression invitro and in transgenic mice by an LXR element (2000) J.Clin. Investig., 105 (4), pp. 513-520Christison, J.K., Rye, K.A., Stocker, R., Exchange of oxidized cholesteryl linoleate between LDL and HDL mediated by cholesteryl ester transfer protein (1995) J.Lipid Res., 36 (9), pp. 2017-2026Matsunaga, T., Hokari, S., Koyama, I., Harada, T., Komoda, T., NF-kappa B activation in endothelial cells treated with oxidized high-density lipoprotein (2003) Biochem. Biophys. Res. Commun., 303 (1), pp. 313-319Ohmura, H., Watanabe, Y., Hatsumi, C., Sato, H., Daida, H., Mokuno, H., Possible role of high susceptibility of high-density lipoprotein to lipid peroxidative modification and oxidized high-density lipoprotein in genesis of coronary artery spasm (1999) Atherosclerosis, 142 (1), pp. 179-184Besler, C., Heinrich, K., Rohrer, L., Doerries, C., Riwanto, M., Shih, D.M., Mechanisms underlying adverse effects of HDL on eNOS-activating pathways in patients with coronary artery disease (2011) J.Clin. Investig., 121 (7), pp. 2693-2708Luscher, T.F., Taddei, S., Kaski, J.C., Jukema, J.W., Kallend, D., Munzel, T., Vascular effects and safety of dalcetrapib in patients with or at risk of coronary heart disease: the dal-VESSEL randomized clinical trial (2012) Eur. Heart J., 33 (7), pp. 857-865Ehara, S., Ueda, M., Naruko, T., Haze, K., Itoh, A., Otsuka, M., Elevated levels of oxidized low density lipoprotein show a positive relationship with the severity of acute coronary syndromes (2001) Circulation, 103 (15), pp. 1955-1960Norata, G.D., Ongari, M., Uboldi, P., Pellegatta, F., Catapano, A.L., Liver X receptor and retinoic X receptor agonists modulate the expression of genes involved in lipid metabolism in human endothelial cells (2005) Int. J. Mol. Med., 16 (4), pp. 717-722Ray, K.K., Ditmarsch, M., Kallend, D., Niesor, E.J., Suchankova, G., Upmanyu, R., The effect of cholesteryl ester transfer protein inhibition on lipids, lipoproteins, and markers of HDL function after an acute coronary syndrome: the dal-ACUTE randomized trial (2014) Eur. 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CYBA C242T polymorphism is associated with obesity and diabetes mellitus in Brazilian hypertensive patients

The CYBA C242T polymorphism has been associated with cardiovascular phenotypes such as hypertension and atherosclerosis, but available data are conflicting. This report investigated the impact of this variant on hypertension and metabolic determinants of cardiovascular risk in a large Brazilian sample. We cross‐sectionally evaluated 1856 subjects (826 normotensive subjects and 1030 hypertensive patients) by clinical history, anthropometry, laboratory analysis and genotyping of the CYBA C242T polymorphism. Genotype frequencies in the whole population were consistent with the Hardy–Weinberg equilibrium and genotype distributions were not different between hypertensive and normotensive subjects. Hypertensive patients with the CC genotype presented lower fasting plasma glucose levels (5.9 ± 0.1 vs. 6.2 ± 0.1 mmol/l, P = 0.020) and waist circumference (94.5 ± 0.6 vs. 96.3 ± 0.6 cm, P = 0.028) than CT + TT ones. Similarly, the prevalence of diabetes mellitus and obesity was also lower in hypertensive patients carrying the CC genotype (16% vs. 21%, P = 0.041; 36% vs. 43%, P = 0.029, respectively). In addition, multiple and logistic regression analysis demonstrated that the CYBA C242T polymorphism was associated with glucose levels, waist circumference, obesity and diabetes mellitus in hypertensive patients independently of potential confounders. Conversely, in normotensive subjects, no significant difference in studied variables was detected between the genotype groups. These data suggest that the T allele of the CYBA C242T polymorphism may be used as a marker for adverse metabolic features in Brazilian subjects with systemic hypertension297e55e61CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP474966/2010‐0; 474966/2010‐02010/16252‐

Low Hdl Cholesterol But Not High Ldl Cholesterol Is Independently Associated With Subclinical Coronary Atherosclerosis In Healthy Octogenarians

Aim of the study Although low-density lipoprotein cholesterol (LDL-C) has been consistently demonstrated a predictor of atherosclerotic disease in a large spectrum of clinical settings, among individuals aged of 80 years or older this concept is uncertain. This study was evaluated in a carefully selected population if the association between LDL-C and coronary atherosclerotic burden remains significant in the very elderly. Methods Individuals aged of 80 years or older (n = 208) who spontaneously sought primary prevention care and have never manifested cardiovascular disease, malnutrition, neoplastic or consumptive disease were enrolled for a cross-sectional analysis. Medical evaluation, anthropometric measurements, blood tests and cardiac computed tomography were obtained. Results In analyses adjusted for age, gender, diabetes, systolic and diastolic blood pressure, smoking and statin therapy, no association was found between coronary calcium score (CCS) and LDL-C [1.79 (0.75-4.29)]. There was no association between triglycerides and CCS. The association between high-density lipoprotein cholesterol (HDL-C) and CCS was significant and robust in unadjusted [0.32 (0.15-0.67)] as well as in the fully adjusted analysis [0.34 (0.15-0.75)]. Conclusion The present study confirms in a healthy cohort of individuals aged of 80 years or more that while the association between LDL-C and coronary atherosclerosis weakens with aging, the opposite occurs with the levels of HDL-C. © 2014 Springer International Publishing Switzerland

Excess weight mediates changes in HDL pool that reduce cholesterol efflux capacity and increase antioxidant activity

Background and Aim: Obesity-related decline in high-density lipoprotein (HDL) functions such as cholesterol efflux capacity (CEC) has supported the notion that this lipoprotein dysfunction may contribute for atherogenesis among obese patients. We investigated if potentially other HDL protective actions may be affected with weight gain and these changes may occur even before the obesity range in a cross-sectional analysis. Methods and Results: Lipid profile, body mass index (BMI), biochemical measurements, and carotid intima-media thickness (cIMT) were obtained in this cross-sectional study with 899 asymptomatic individuals. Lipoproteins were separated by ultracentrifugation and HDL physical-chemical characterization, CEC, antioxidant activity, anti-inflammatory activity, HDL-mediated platelet aggregation inhibition were measured in a randomly-selected subgroup (n = 101). Individuals with increased HDL-C had an attenuated increase in cIMT with elevation of BMI (interaction effect β = −0.054; CI 95% −0.0815, −0.0301). CEC, HDL-C, HDL size and HDL-antioxidant activity were negatively associated with cIMT. BMI was inversely correlated with HDL-mediated inhibition of platelet aggregation (Spearman's rho −0.157, p &lt; 0.03) and CEC (Spearman's rho −0.32, p &lt; 0.001), but surprisingly it was directly correlated with the antioxidant activity (Spearman's rho 0.194, p = 0.052). Thus, even in non-obese, non-diabetic individuals, increased BMI is associated with a wide change in protective functions of HDL, reducing CEC and increasing antioxidant activity. In these subjects, decreased HDL concentration, size or function are related to increased atherosclerotic burden. Conclusion: Our findings demonstrate that in non-obese, non-diabetic individuals, the increasing values of BMI are associated with impaired protective functions of HDL and concomitant increase in atherosclerotic burden

Monocytes of patients with unstable angina express high levels of chemokine and pattern-recognition receptors

Macrophages derived from monocytes play an important role in atherosclerosis progression. Subpopulations of circulating classical, intermediate, and non-classical monocytes possess distinct functions and phenotypes, and participate in the pathogenesis of disease. The aim of this study was to compare the quantity and phenotypes of circulating monocyte subpopulations in patients with established atherosclerosis and healthy control individuals. Additionally, the study aimed to provide insight into the functional activity of monocytes against a heat shock protein (HSP60). Methods: Chemokine and pattern recognition receptors in monocyte subsets obtained from peripheral blood of acute and chronic coronary artery disease patients and controls were quantified by flow cytometry. Furthermore, monocytes from healthy controls were stimulated in vitro with HSP60, and the cytokines produced by them were evaluated by flow cytometry. Results: Eighteen controls (C), 34 individuals with risk factors for cardiovascular disease (RF), 32 patients with stable angina (SA), and 16 patients with unstable angina (UA) were enrolled in the study. The absolute count of intermediate monocytes was found to be increased in patients of the UA group; high frequencies of the chemokine receptors CCR2, CCR5, and CX3CR1 were also observed in this subpopulation. Moreover, the pattern recognition receptors TLR2 and TLR4 were more frequent in intermediate monocytes from the UA group. Furthermore, the intermediate monocytes from healthy individuals produced IL-12p70 after stimulation with HSP60. Conclusions: Our results show that intermediate monocytes of UA patients exhibited an enhanced expression of the receptors involved in the recognition of damage-associated molecular patterns (DAMPs) and enhancement of the migratory function. Hence, they might contribute to the propagation and progression of inflammation observed in atherosclerosis, especially in the acute setting.1136167CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP308746/2013-92014/00327-