RESUMEN
AIM: While smoking cessation (SC) leads to a reduction of cardiovascular events, atherogenic biomarkers specifically connected with cigarette smoking and SC are unknown. Circulating levels of oxidatively modified low-density-lipoprotein (LDL) are associated with a high risk of cardiovascular diseases. Recently, two novel, oxidatively modified LDL markers, serum amyloid A-LDL (SAA-LDL) and α1-antitrypsin-LDL (AT-LDL), were identified; however, the significance of SAA-LDL and AT-LDL as cardiovascular risk markers is unknown. METHODS: We carried out a cross-sectional study involving 243 patients, and determined serum levels of SAA-LDL and AT-LDL. RESULTS: Both serum levels of SAA-LDL and AT-LDL were significantly increased in current compared to non-current smokers. Stepwise regression analysis revealed that the current smoking status and duration of smoking were strong independent determinants of the AT-LDL level. In contrast, high-sensitivity C-reactive protein was the strongest determinant of the SAA-LDL level. In multiple logistic regression analysis, the current smoking status was most closely associated with the AT-LDL level. Successful SC employing a 12-week program significantly increased the body mass index and serum levels of obesity-related markers. Notably, successful SC significantly decreased levels of AT-LDL, but not those of SAA-LDL. CONCLUSIONS: The present study provides the first evidence for the distinct characteristics of two novel, oxidatively modified LDL markers, SAA-LDL and AT-LDL. In contrast to SAA-LDL, an inflammatory marker, AT-LDL serves as a marker of smoking-specific oxidative stress. These findings warrant further investigations to clarify if AT-LDL provides a key link between smoking and cardiovascular diseases.
Asunto(s)
Biomarcadores/sangre , Lipoproteínas LDL/sangre , Estrés Oxidativo , Inhibidores de Serina Proteinasa/sangre , Proteína Amiloide A Sérica/metabolismo , Fumar/sangre , alfa 1-Antitripsina/sangre , Adipoquinas/sangre , Índice de Masa Corporal , Proteína C-Reactiva/metabolismo , Estudios Transversales , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Fumar/efectos adversos , Factor A de Crecimiento Endotelial Vascular/sangreRESUMEN
The mechanisms that lead from obesity to atherosclerotic disease are not fully understood. Obesity involves angiogenesis in which vascular endothelial growth factor-A (VEGF-A) plays a key role. On the other hand, vascular endothelial growth factor-C (VEGF-C) plays a pivotal role in lymphangiogenesis. Circulating levels of VEGF-A and VEGF-C are elevated in sera from obese subjects. However, relationships of VEGF-C with atherosclerotic risk factors and atherosclerosis are unknown. We determined circulating levels of VEGF-A and VEGF-C in 423 consecutive subjects not receiving any drugs at the Health Evaluation Center. After adjusting for age and gender, VEGF-A levels were significantly and more strongly correlated with the body mass index (BMI) and waist circumference than VEGF-C. Conversely, VEGF-C levels were significantly and more closely correlated with metabolic (e.g., fasting plasma glucose, hemoglobin A1c, immunoreactive insulin, and the homeostasis model assessment of insulin resistance) and lipid parameters (e.g., triglycerides, total cholesterol (TC), low-density-lipoprotein cholesterol (LDL-C), and non-high-density-lipoprotein cholesterol (non-HDL-C)) than VEGF-A. Stepwise regression analyses revealed that independent determinants of VEGF-A were the BMI and age, whereas strong independent determinants of VEGF-C were age, triglycerides, and non-HDL-C. In apolipoprotein E-deficient mice fed a high-fat-diet (HFD) or normal chow (NC) for 16 weeks, levels of VEGF-A were not significantly different between the two groups. However, levels of VEGF-C were significantly higher in HFD mice with advanced atherosclerosis and marked hypercholesterolemia than NC mice. Furthermore, immunohistochemistry revealed that the expression of VEGF-C in atheromatous plaque of the aortic sinus was significantly intensified by feeding HFD compared to NC, while that of VEGF-A was not. In conclusion, these findings demonstrate that VEGF-C, rather than VEGF-A, is closely related to dyslipidemia and atherosclerosis.
Asunto(s)
Factor A de Crecimiento Endotelial Vascular/sangre , Factor C de Crecimiento Endotelial Vascular/sangre , Animales , Apolipoproteínas E/deficiencia , Femenino , Regulación de la Expresión Génica , Humanos , Metabolismo de los Lípidos , Masculino , Ratones , Persona de Mediana Edad , Placa Aterosclerótica/sangre , Placa Aterosclerótica/metabolismoRESUMEN
BACKGROUND: Cigarette smoking is an independent risk factor for cardiovascular events such as myocardial infarction and stroke. To date, a useful and convenient method of predicting such events in smokers has not been established. The rheological properties of blood assessed by the microchannel method reflect the blood's viscosity and the state of microthrombus formation, which may predict cardiovascular thrombotic events. METHODS AND RESULTS: Blood fluidity was assessed in 74 smoking patients (54 men, 20 women, mean age 57.9 years) by measuring the blood passage time (BPT) in an aliquot (100 µl) of blood using the Micro Channel Array Flow Analyzer. BPT was significantly related with smoking variables such as daily consumption of tobacco (r = 0.236, P = 0.044), Brinkman's index (r = 0.252, P = 0.033), the Fagerstrom Test for Nicotine Dependence (r = 0.257, P = 0.029), and the score of a self-rating depression scale (r = 0.236, P < 0.05). Multivariate regression analysis revealed that an independent BPT determinant was daily consumption of tobacco (r = 0.326, P = 0.045). Furthermore, smoking cessation markedly decreased BPT from 63.0 s to 49.7 s (P = 0.002) at 3 months after the start of therapy. CONCLUSIONS: Unfavorable blood rheology is closely associated with cigarette smoking and may reflect increased cardiovascular risk in smokers. The study results also suggest that such risk can be reduced after only 3 months of smoking cessation.
Asunto(s)
Viscosidad Sanguínea , Enfermedades Cardiovasculares/prevención & control , Cese del Hábito de Fumar , Prevención del Hábito de Fumar , Fumar/sangre , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/etiología , Femenino , Conductas Relacionadas con la Salud , Conocimientos, Actitudes y Práctica en Salud , Hemorreología , Humanos , Japón , Modelos Logísticos , Masculino , Persona de Mediana Edad , Motivación , Medición de Riesgo , Factores de Riesgo , Fumar/efectos adversos , Fumar/psicología , Cese del Hábito de Fumar/psicología , Factores de TiempoRESUMEN
OBJECTIVE: Metabolic syndrome (MetS) is associated with impaired angiogenesis. Vascular endothelial growth factor (VEGF) plays a key role in angiogenesis through binding to its specific receptor, VEGF receptor-2 (VEGFR-2), whereas the expression of VEGF and VEGFR-2 in the myocardium of insulin-resistant rats is down-regulated. Soluble VEGF receptor-1 (sVEGFR-1) and -2 (sVEGFR-2) have been reported to inhibit angiogenesis both in vitro and in vivo. However, the balance between circulating levels of VEGF and its soluble receptors, which may reflect and/or affect cardiovascular VEGF signaling, in subjects with MetS is unknown. METHODS AND RESULTS: We carried out a cross-sectional study including 272 consecutive, apparently healthy subjects who were not receiving any drugs. Plasma levels of VEGF and serum levels of its soluble receptors were determined using enzyme-linked immunosorbent assays. VEGF and sVEGFR-1 levels did not differ between subjects with and those without MetS. However, sVEGFR-2 levels were significantly increased in MetS compared with non-MetS subjects. Stepwise regression analysis revealed that HOMA-IR was the strongest independent determinant of the sVEGFR-2 level. Accordingly, the mean sVEGFR-2 levels increased in proportion to both the accumulation of components of MetS and quartile of HOMA-IR. Interestingly, multiple regression analyses revealed that independent determinants of VEGF were the body mass index and blood pressure, whereas, in contrast, those of sVEGFR-2 were HOMA-IR and high-sensitivity C-reactive protein. CONCLUSIONS: The correlation of sVEGFR-2 with insulin resistance supports the need for further investigations to define the clinical utility and predictive value of serum sVEGFR-2 levels in cardiovascular dysfunction in MetS.
Asunto(s)
Resistencia a la Insulina , Síndrome Metabólico/sangre , Receptor 2 de Factores de Crecimiento Endotelial Vascular/sangre , Adulto , Estudios Transversales , Regulación hacia Abajo , Femenino , Humanos , Insulina/metabolismo , Masculino , Persona de Mediana Edad , Modelos Biológicos , Miocardio/patología , Neovascularización Patológica/sangre , Transducción de Señal , Factor A de Crecimiento Endotelial Vascular/metabolismo , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismoRESUMEN
BACKGROUND/AIMS: It is still unclear whether and how Th1/Th2 type cytokines are involved in the progression of chronic liver disease type C. We therefore examined serum levels of IL-10, IL-12 and sIL-2R (soluble IL-2 receptor) in association with clinical parameters in chronic liver disease type C, whereas IL-12 and sIL-2R represent Th1 cytokine and IL-10 does Th2 cytokine, respectively. METHODOLOGY: Serum levels of IL-10, IL-12 and sIL-2R were measured in 110 patients, including 36 with chronic hepatitis, 24 with liver cirrhosis and 50 with hepatocellular carcinoma in comparison with 19 normal individuals, by an enzyme-linked immunosorbent assay. In 9 chronic hepatitis patients, serum levels of these cytokines were measured before and after interferon therapy. In 28 with hepatocellular carcinoma, they were also measured before and after transcatheter arterial embolization. RESULTS: Serum levels of IL-10 in chronic hepatitis, liver cirrhosis and hepatocellular carcinoma were 3.9 +/- 1.8 pg/mL, 5.7 +/- 6.4 pg/mL and 5.6 +/- 8.9 pg/mL, respectively. IL-10 level was significantly correlated with level of y-globulin. Serum levels of IL-12 in chronic hepatitis, liver cirrhosis and hepatocellular carcinoma were 347.4 +/- 150.3 pg/mL, 365.2 +/- 130.7 pg/mL and 399.4 +/- 258.2 pg/mL. sIL-2R levels in chronic hepatitis, liver cirrhosis and hepatocellular carcinoma were 614.6 +/- 223.5 U/mL, 878.7 +/- 330.5 U/mL and 1037.9 +/- 412.0 U/mL. Serum levels of IL-12 and sIL-2R were significantly elevated on day 7 after interferon therapy compared to day 0 (p < 0.05 and p < 0.001, respectively), while no significant difference was seen in IL-10. Serum level of IL-10 was significantly elevated on day 3, and that of sIL-2R was elevated on day 3 and 7 after transcatheter arterial embolization, while that of IL-12 was decreased on day 3 and 7. CONCLUSIONS: The results of the present study suggest that Th1/Th2 type cytokines are changed in association with progression of chronic liver disease type C and in response to therapy.