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Background: Hyperhomocysteinemia (HHcy) is an independent risk factor for atherosclerosis. Effective interventions to reduce HHcy-accelerated atherosclerosis are required. Objectives: This study aimed to investigate the effects of aerobic exercise (AE) and folate (FA) supplementation on plasma homocysteine (Hcy) level and atherosclerosis development in a mouse model. Methods: Six-week-old female apoE-/- mice were grouped into five groups (N = 6-8): HHcy (1.8 g/L DL-homocysteine (DL-Hcy) in drinking water), HHcy + AE (1.8 g/L DL-Hcy and aerobic exercise training on a treadmill), HHcy + FA (1.8 g/L DL-Hcy and 0.006% folate in diet), HHcy + AE + FA (1.8 g/L DL-Hcy, 0.006% folate, and aerobic exercise training on a treadmill), and a control group (regular water and diet). All treatment was sustained for 8 weeks. Triglyceride, cholesterol, lipoprotein, and Hcy levels were determined enzymatically. Plaque and monocyte chemoattractant protein-1 (MCP-1) expression levels in mouse aortic roots were evaluated by immunohistochemistry. Results: Compared to the HHcy group (18.88 ± 6.13 µmol/L), plasma Hcy concentration was significantly reduced in the HHcy + AE (14.79 ± 3.05 µmol/L, p = 0.04), HHcy + FA (9.4 ± 3.85 µmol/L, p < 0.001), and HHcy + AE + FA (9.33 ± 2.21 µmol/L, p < 0.001) groups. Significantly decreased aortic root plaque area and plaque burden were found in the HHcy + AE and HHcy + AE + FA groups compared to those in the HHcy group (both p < 0.05). Plasma MCP-1 level and MCP-1 expression in atherosclerotic lesions were significantly decreased in the HHcy + AE and HHcy + AE + FA groups compared to the HHcy group (all p < 0.05). Conclusions: AE reduced atherosclerosis development in HHcy apoE-/- mice independently of reducing Hcy levels. FA supplementation decreased plasma Hcy levels without attenuating HHcy-accelerated atherosclerosis. AE and FA supplementation have distinct mechanisms in benefiting atherosclerosis.
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OBJECTIVE: To observe the multiple influence of cholesterol-lowering drug (simvastatin) on ankle brachial index (ABI), flow-mediated dilation (FMD) and nitroglycerin-mediated dilation (NMD) of brachial artery blood vessel endothelium, and plasma level of monocyte chemotactic protein 1 (MCP-1) of hypercholesterolemia patients without coronary heart disease (CHD). METHODS: In the study, 51 patients with hypercholesterolemia application were treated with simvastatin (20 mg/d) therapy for 12 weeks. The metabolic index, ankle brachial index (ABI), FMD of brachial artery blood vessel endothelium detected by color doppler ultrasound instrument, the NMD of artery endothelial and the level of MCP 1 were measured before and after therapy respectively. All the results were analyzed and compared with another 30 cases of hypercholesterolemia patients selected without simvastatin treatment. RESULTS: After simvastatin therapy, the TC (total cholesterol) and LDL-C (low density lipoprotein cholesterin) levels were reduced apparently,the values decreased from the original (6.06 ± 1.03) mmol/L and (3.60 ± 0.82) mmol/L to (4.98 ± 1.34) mmol/L and (3.41 ± 0.10) mmol/L respectively (P<0.01, P< 0.05). Compared with no simvastatin treatment, the bilateral ABI levels were significantly elevated. The right side of ABI (ABIR) elevated from 1.11 ± 0.06 to 1.19 ± 0.07, and the left side of ABI (ABIL) also elevated from 1.12 ± 0.06 to 1.19 ± 0.10 (both sides were P<0.01). The FMD significantly increased from 7.75% ± 11.30% to 14.20% ± 15.39% (P < 0.05). The plasma levels of MCP-1 were apparently reduced from (112.0 ± 7.8) ng/L to (108.9 ± 6.2) ng/L (P < 0.05). All these items showed no obvious change within the control group. CONCLUSION: The API, FMD and plasma levels of MCP-1 of hypercholesterolemia patients without clear coronary heart disease can be improved by simvastatin treatment.
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Anticolesterolemiantes/farmacología , Endotelio Vascular/efectos de los fármacos , Hipercolesterolemia/tratamiento farmacológico , Simvastatina/farmacología , Índice Tobillo Braquial , Arteria Braquial/patología , Estudios de Casos y Controles , Quimiocina CCL2/sangre , Colesterol/sangre , Enfermedad Coronaria , Humanos , VasodilataciónRESUMEN
OBJECTIVE: Coronary flow velocity reserve (CFVR) is an important indicator of coronary endothelial functions and microcirculation. Pulse wave velocity (PWV) reflects the degree of aortic sclerosis and it is an independent predictor of cardiovascular events. The present study was designed to evaluate the correlation of large artery stiffness and CFVR. METHODS: A total of 101 consecutive subjects were enrolled to measure the brachial-ankle pulse wave velocity (baPWV). According to the presence or absence of higher baPWV (> 1400 cm/s), they were divided into 2 groups. Transthoracic echocardiography was employed to measure coronary flow velocity in coronary left anterior descending (LAD). Then after an intravenous infusion of adenosine triphosphate, the velocity of blood flow was measured when the vessel was in maximal dilation. The ratio of flow velocity of those in maximal dilation to those at rest was CFVR. RESULTS: The subjects with a higher baPWV (> 1400 cm/s) were markedly elder and had higher risks of hypertension and diabetes. Thus age, hypertension and diabetes contributed to arteriosclerosis. More importantly, the subjects with a higher baPWV (> 1400 cm/s) had a much lower level of CFVR (2.66 ± 0.74 vs 2.95 ± 0.76; P < 0.01) than those with a lower baPWV (< 1400 cm/s). Furthermore correlation analysis showed that CFVR and baPWV levels were significantly negatively correlated (r = -0.35, P < 0.01). CONCLUSIONS: A negative correlation exists between artery stiffness and coronary flow velocity reserve. The increased vascular stiffness may impair coronary endothelial function, cause the dysfunction of coronary microcirculation and raise the risks of cardiovascular events.
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Enfermedad de la Arteria Coronaria/fisiopatología , Vasos Coronarios/fisiopatología , Rigidez Vascular , Anciano , Velocidad del Flujo Sanguíneo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis de la Onda del PulsoRESUMEN
Rad is a member of a subclass of small GTP-binding proteins, the RGK family. In the present study we investigated the role of Rad protein in regulating cardiomyocyte viability. DNA fragmentation and TUNEL assays demonstrated that Rad promoted rat neonatal cardiomyocyte apoptosis. Rad silencing fully blocked serum deprivation induced apoptosis, indicating Rad is necessary for trigger cardiomyocyte apoptosis. Rad overexpression caused a dramatic decrease of the anti-apoptotic molecule Bcl-x(L), whereas Bcl-x(L) overexpression protected cardiomyocytes against Rad-induced apoptosis. Rad-triggered apoptosis was mediated by the activation of p38 MAPK. The p38 blocker SB203580 effectively protected cardiomyocytes against Rad-evoked apoptosis.
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Apoptosis , Miocitos Cardíacos/enzimología , Miocitos Cardíacos/fisiología , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Proteínas ras/metabolismo , Animales , Supervivencia Celular , Células Cultivadas , Imidazoles/farmacología , Miocitos Cardíacos/efectos de los fármacos , Inhibidores de Proteínas Quinasas/farmacología , Piridinas/farmacología , ARN Interferente Pequeño/genética , Ratas , Proteínas Quinasas p38 Activadas por Mitógenos/antagonistas & inhibidores , Proteínas ras/genéticaRESUMEN
OBJECTIVE: To investigate the effects of advanced glycation end products (AGEs) on the secretion of monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) in vascular smooth muscle cells (VSMCs) and explore its possible intracellular signaling mechanism. METHODS: Primary rat VSMCs were isolated and identified. VSMCs were treated with glycation serum albumin (GSA), an important component of AGEs, in series of concentrations and time. The role of MAPK and NF-κB inhibitors was confirmed. The levels of MCP-1 and IL-8 were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: VSMCs were treated with GSA at the doses of 10 µg/ml, 100 µg/ml and 500 µg/ml respectively. In comparison with the control group, the levels of MCP-1 (13.01 ng/ml ± 0.12 ng/ml vs 7.02 ng/ml ± 0.26 ng/ml, P < 0.05) and IL-8 (12.6 ng/ml ± 0.86 ng/ml vs 3.07 ng/ml ± 0.35 ng/ml, P < 0.05) increased in the GSA-treated group, especially at the concentration of 100 µg/ml. After adjustment for cells proliferation, the levels of MCP-1 and IL-8 were still higher in the GSA-treated group. After a pretreatment of PDTC (10 µmol/L), SB203580 (5 µmol/L) and MG132 (10 µmol/L), the levels of MCP-1 and IL-8 decreased. However, it had no change when pretreated with PD98059 (20 µmol/L). CONCLUSION: GSA promotes the secretion of MCP-1 and IL-8 in VSMCs. Such an effect is not dependent on cellular proliferation. It may be realized through an activation of NF-κB by p38MAPK-sensitive intracellular signaling pathway.
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Quimiocina CCL2/metabolismo , Productos Finales de Glicación Avanzada/farmacología , Interleucina-8/metabolismo , Músculo Liso Vascular/metabolismo , Miocitos del Músculo Liso/metabolismo , Animales , Masculino , Músculo Liso Vascular/citología , Músculo Liso Vascular/efectos de los fármacos , Miocitos del Músculo Liso/efectos de los fármacos , Ratas , Ratas WistarRESUMEN
Hyperhomocysteinemia (HHcy) has been associated with impaired vascular endothelial function. Our previous study demonstrated significantly higher secretion of the chemokine monocyte chemoattractant protein-1 from monocytes in response to lipopolysaccharide in patients with HHcy. In the present study, we investigated whether coronary endothelial function was damaged in patients with chronic HHcy (plasma level of homocysteine >15 µmol/l) and, if so, whether this impaired endothelial function is induced by the uncoupling of endothelial nitric oxide synthase (eNOS). When tetrahydrobiopterin levels are inadequate, eNOS is no longer coupled to l-arginine oxidation, which results in reactive oxygen species rather than nitric oxide production, thereby inducing vascular endothelial dysfunction. The 71 participants were divided into two groups, control (n = 50) and HHcy (n = 21). Quantification of coronary flow velocity reserve (CFVR) was after rest and after adenosine administration done by noninvasive Doppler echocardiography. Plasma levels of nitric oxide and tetrahydrobiopterin were significantly lower in patients with HHcy than in controls (99.54 ± 32.23 vs. 119.50 ± 37.68 µmol/l and 1.43 ± 0.46 vs. 1.73 ± 0.56 pmol/ml, all P < 0.05). Furthermore, CFVR was significantly lower in the HHcy than the control group (2.76 ± 0.49 vs. 3.09 ± 0.52, P < 0.05). In addition, plasma level of homocysteine was negatively correlated with CFVR. Chronic HHcy may contribute to coronary artery disease by inducing dysfunction of the coronary artery endothelium. The uncoupling of eNOS induced by HHcy in patients with chronic HHcy may explain this adverse effect in part.
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Biopterinas/análogos & derivados , Vasos Coronarios/fisiopatología , Endotelio Vascular/fisiopatología , Homocisteína/metabolismo , Hiperhomocisteinemia/fisiopatología , Adulto , Anciano , Biopterinas/metabolismo , Velocidad del Flujo Sanguíneo , Cromatografía Líquida de Alta Presión , Vasos Coronarios/metabolismo , Endotelio Vascular/metabolismo , Femenino , Humanos , Hiperhomocisteinemia/metabolismo , Masculino , Persona de Mediana Edad , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo III/metabolismo , Estadísticas no ParamétricasRESUMEN
Arterial stiffness is an independent risk factor for cardiovascular events in diabetic patients, and it can be assessed by measuring pulse wave velocity (PWV). We investigated the degree of arterial stiffness in diabetic patients with coronary artery disease (CAD) and the effect of the proliferator-activated receptor gamma (PPAR-gamma) agonist rosiglitazone on arterial stiffness in the potential mechanism of anti-arteriosclerosis in patients with type 2 diabetes mellitus and CAD. The 123 participants were divided into 3 groups: healthy controls (n = 36), diabetic patients (n = 41), and diabetic patients with CAD (n = 46). Forty-six diabetic patients with CAD were randomly divided into 2 groups: untreated diabetic patients with CAD and diabetic patients with CAD treated with 4 mg/d of rosiglitazone (n = 25) for 12 weeks. Pulse wave velocity was measured before treatment and at 12-week follow-up. Baseline PWV was significantly higher in patients with diabetes, diabetes and CAD, and diabetes and CAD with treatment as compared with the healthy control group (1,633 +/- 37.3, 1,669 +/- 53.8, 1,615 +/- 44.4, and 1,360 +/- 39.9 cm/s, respectively, P < .001). Pulse wave velocity in the rosiglitazone-treated group was significantly reduced, from 1,615 +/- 44.4 to 1,525 +/- 43.1 cm/s, after 12-week treatment, Furthermore, PWV was significantly decreased in the rosiglitazone-treated group compared with untreated group after 12 weeks (1525 +/- 43.1 and 1,670 +/- 41.3 cm/s, respectively). Pulse wave velocity in the untreated group did not differ from baseline levels after 12 weeks. In addition, plasma C-reactive protein level was decreased significantly in the rosiglitazone-treated group compared with values at baseline and for the untreated group after 12 weeks (0.73 +/- 0.09, 1.71 +/- 0.24, and 1.33 +/- 0.29 mg/L, respectively). Plasma level of monocyte chemoattractant protein 1 was decreased in the rosiglitazone group compared with the level at baseline (392 +/- 42 and 273 +/- 40 pg/mL, respectively). Moreover, the decrease in PWV was associated linearly both with improved homeostasis model assessment of insulin resistance and with decreased C-reactive protein level after PPAR-gamma agonist treatment. In conclusion, PPAR-gamma agonist rosiglitazone treatment may significantly decrease arterial stiffness in diabetic patients with CAD. Proliferator-activated receptor gamma agonists may play an important role in protecting against arteriosclerosis by normalizing the metabolic disorders and depressing chronic inflammation of the vascular system in patients with type 2 diabetes mellitus and serious vascular disease.
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Arterias/efectos de los fármacos , Arterias/patología , Enfermedad Coronaria/tratamiento farmacológico , Enfermedad Coronaria/patología , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/patología , Hipoglucemiantes/uso terapéutico , PPAR gamma/agonistas , Tiazolidinedionas/uso terapéutico , Adulto , Anciano , Antiinflamatorios no Esteroideos/farmacología , Velocidad del Flujo Sanguíneo/fisiología , Proteína C-Reactiva/metabolismo , Quimiocina CCL2/sangre , Enfermedad Coronaria/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Femenino , Hemoglobinas/metabolismo , Humanos , Lípidos/sangre , Masculino , Persona de Mediana Edad , RosiglitazonaRESUMEN
Hyperglycemia, advanced glycation end products (AGEs), hyperinsulinemia and dyslipidemia may play roles in the development of diabetes-associated atherosclerosis and post-angioplasty restenosis. Clinically, their effects seem to be synergic. However, few studies have focused on the synergistic action of these factors. In the present study, we investigated whether glycated serum albumin (GSA) has a synergistic effect with insulin on the proliferation of vascular smooth muscle cells (VSMCs). VSMCs were isolated from rat thoracic aortas and cultured in fetal bovine serum (FBS)-free medium for 24 h, then exposed to GSA, insulin or GSA + insulin for 48 h with or without pretreatment of mitogen-activated protein kinase (MAPK) inhibitors or the antioxidant N-acetylcysteine (NAC). Cell growth rate was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay or cell counting. The changes of phosphorylated-p38 MAPK and phosphorylated-C-Jun N-terminal kinase 1/2 (JNK1/2) were measured by Western blot analysis. The results showed that only p38 MAPK, but not JNK was activated by GSA and insulin co-incubation. VSMC proliferation was increased by insulin (10-1000 nmol/L) or GSA (10, 100 microg/mL). Co-incubation of insulin (100 nmol/L) and GSA (100 mug/mL) caused a more potent increase in VSMC proliferation than insulin or GSA incubation alone. p38 MAPK inhibitor, SB203580, as well as NAC, could inhibit the VSMC proliferation induced by co-incubation of GSA and insulin. The results show that insulin enhances GSA-induced VSMC proliferation, which may be mediated through a reactive oxygen species (ROS)-p38 MAPK pathway. The synergism of AGEs and insulin may play a detrimental role in the pathogenesis of diabetic atherosclerosis and post-angioplasty restenosis.
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Proliferación Celular/efectos de los fármacos , Insulina/fisiología , Músculo Liso Vascular/citología , Miocitos del Músculo Liso/citología , Albúmina Sérica/fisiología , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Animales , Aorta Torácica/citología , Células Cultivadas , Sinergismo Farmacológico , Productos Finales de Glicación Avanzada , Insulina/farmacología , Masculino , Miocitos del Músculo Liso/efectos de los fármacos , Fosforilación , Ratas , Ratas Sprague-Dawley , Albúmina Sérica/farmacología , Albúmina Sérica GlicadaRESUMEN
OBJECTIVE: To investigate the anti-apoptotic effects of mesenchymal stem cells (MSCs) on hypoxia-injured cardiac myocytes. METHODS: MSCs were isolated from the bone marrow of 6 - 8 week-old Sprague-Dawley rats. Cardiac myocytes from neonatal rat were cultured under hypoxia, then the hypoxia-injured cardiac myocytes were divided into 3 groups: cultured alone (control group), co-cultured with the MSCs, or co-cultured in MSC-conditioned media in conditions of anoxia (95% N(2) + 5% CO(2), continuous hypoxia group) or normoxia [hypoxia/reoxygen (H/R) group] for 72 hours. The cell apoptosis was measured by Hoechst staining, and Western blotting was used to test the protein expression of Bcl-2 and Bax in the cardiac myocytes. RESULTS: The apoptotic rate of the cardiac myocytes cultured under hypoxia was 51.6% +/- 2.4%, significantly higher than those of the cardiac myocytes co-cultured with MSCs and MSC-conditioned media respectively (15.1% +/- 5.4% and 24.0% +/- 4.2% respectively, both P < 0.001). The apoptotic rate of the H/R group was 20.9% +/- 2.7%, significant higher than that of the MSC group (11.5% +/- 3.7%, P < 0.05), however, not significantly different from that of the MSC-conditioned media group (20.1% +/- 4.2%, P > 0.05). The protein expression of Bcl-2 was not significantly different among different groups. The Bax protein expression of the MSC group and MSC-conditioned media group were 2.28 +/- 0.46 and 3.01 +/- 0.26 respectively, both significantly lower than that of the control group (7.62 +/- 1.28, both P < 0.05). The decreased expression of Bax in the cardiac myocytes was greatly related to the decreasing of apoptosis. CONCLUSION: Co-cultured MSCs show significant anti-apoptotic effects on cardiac myocytes both in continuous hypoxia and in H/R conditions with the possible mechanism of direct cell to cell interaction and paracrine of cytokines which effect the expression of Bax in the myocytes.
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Apoptosis , Células Madre Mesenquimatosas/citología , Miocitos Cardíacos/citología , Animales , Animales Recién Nacidos , Western Blotting , Células de la Médula Ósea/citología , Hipoxia de la Célula , Células Cultivadas , Técnicas de Cocultivo , Masculino , Células Madre Mesenquimatosas/metabolismo , Miocitos Cardíacos/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/biosíntesis , Ratas , Ratas Sprague-Dawley , Proteína X Asociada a bcl-2/biosíntesisRESUMEN
OBJECTIVE: To investigate the effect of folic acid on homocysteine (Hcy)-induced chemokine secretion and NADPH oxidase activity in human monocytes. METHODS: Human monocytes from healthy volunteers were incubated with Hcy (100 micromol/L) with or without folic acid (5 micromol/L) for 24 h; MCP-1 and IL-8 were assessed by ELISA. DCFH-DA was added to monitor intracellular ROS production on confocal microscopy. A cytochrome c reduction assay was used to measure NADPH oxidase activity. RESULTS: The Hcy-induced secretion of MCP-1 and IL-8 was significantly reduced by folic acid [(1.88 +/- 0.51) ng/ml vs. (4.36 +/- 0.72) ng/ml vs. (2.40 +/- 0.60) ng/ml and (4.9 +/- 1.9) ng/ml vs. (12.7 +/- 1.5) ng/ml vs. (7.2 +/- 1.9) ng/ml, all P < 0.05]. The Hcy-induced production of ROS was also significantly attenuated by folic acid. Moreover, the Hcy-induced NADPH oxidase activity increase was significantly inhibited by cotreatment with folic acid. CONCLUSION: Folic acid may attenuate oxidative stress induced by Hcy by reducing NADPH oxidase activity in monocytes.
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Quimiocinas/metabolismo , Ácido Fólico/farmacología , Homocisteína/farmacología , Monocitos/metabolismo , NADPH Oxidasas/metabolismo , Células Cultivadas , Humanos , Interleucina-8/metabolismo , Monocitos/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Receptores CCR2/metabolismoRESUMEN
Our previous study demonstrated that homocysteine (Hcy) mediated the expression and secretion of MCP-1 and IL-8 in human monocytes. In the present study, we investigated whether the responsiveness of isolated monocytes to lipopolysaccharide (LPS)-induced chemokine secretion was enhanced in patients with hyperhomocysteinemia (HHcy), and if so, whether this enhanced response could be inhibited by folic acid treatment. We studied 38 control subjects and 40 patients with HHcy. The results showed that MCP-1 secretion from isolated monocytes in response to low-dose LPS in patients with HHcy was significantly higher than that in controls. After patients with HHcy underwent low-dose folic acid treatment (0.8 mg/d) for 6 months, plasma Hcy levels were decreased and the hyper-responsiveness of MCP-1 and IL-8 secreted by isolated monocytes was significantly reversed. Furthermore, folic acid treatment at high concentrations (5 microM) significantly reduced the elevated levels of reactive oxygen species, NADPH oxidase activity and chemokines in response to Hcy in cultured human monocytes. HHcy may contribute to atherogenesis through enhancing the responsiveness of monocytes to inflammatory stimuli and promoting leukocyte recruitment into atherosclerotic plaque. In addition to lowering the plasma levels of Hcy, low-dose folic acid treatment exerts beneficial effects on patients with HHcy by inhibiting pro-inflammatory responses such as chemokine secretion from human monocytes.
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Arteriosclerosis/tratamiento farmacológico , Quimiocinas/metabolismo , Ácido Fólico/farmacología , Hematínicos/farmacología , Lipopolisacáridos/farmacología , Monocitos/fisiología , Arteriosclerosis/inmunología , Estudios de Casos y Controles , Técnicas de Cultivo de Célula , Humanos , Hiperhomocisteinemia , Inflamación , NADPH Oxidasas/farmacologíaRESUMEN
Rosiglitazone, an agonist of peroxisome proliferator-activated receptor-gamma (PPAR gamma ), is an insulin-sensitizing antidiabetic agent and inhibits restenosis in animal blood vessels. However, its benefit for patients with type 2 diabetes and coronary artery disease (CAD) after percutaneous coronary intervention is unknown. Patients with diabetes and CAD who had undergone percutaneous coronary intervention were randomized to either receive or not receive rosiglitazone (4 mg/d) for 6 months. After 6 months of rosiglitazone treatment, the plasma levels of fasting glucose and insulin and those of hemoglobin A1C and homeostasis model assessment of insulin resistance were significantly decreased in the rosiglitazone group as compared with baseline levels and those in the control group. After 2 and 6 months of rosiglitazone treatment, the plasma level of high-density lipoprotein was significantly increased in the rosiglitazone group. In addition, plasma levels of monocyte chemoattractant protein-1 and C-reactive protein and hyperresponsiveness of low-dose lipopolysaccharide-induced monocyte chemoattractant protein-1 secretion from monocytes were reduced. Furthermore, the occurrence of coronary events was significantly decreased in the rosiglitazone group at 6-month follow-up. Our data indicate that rosiglitazone may protect the vascular wall through not only improving the features of metabolic disorders but also reducing proinflammatory responses and the occurrence of coronary events in patients with diabetes and CAD after percutaneous coronary intervention.
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Angioplastia Coronaria con Balón/efectos adversos , Diabetes Mellitus Tipo 2/complicaciones , Angiopatías Diabéticas/terapia , Inflamación/tratamiento farmacológico , PPAR gamma/agonistas , Tiazolidinedionas/uso terapéutico , Anciano , Proteína C-Reactiva/metabolismo , Quimiocina CCL2/sangre , Quimiocinas/sangre , Enfermedad Coronaria/prevención & control , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/fisiopatología , Angiopatías Diabéticas/etiología , Angiopatías Diabéticas/prevención & control , Femenino , Humanos , Inflamación/etiología , Lipopolisacáridos/farmacología , Masculino , Persona de Mediana Edad , Monocitos/efectos de los fármacos , Monocitos/metabolismo , RosiglitazonaRESUMEN
OBJECTIVE: To investigate the changes of electrocardiogram (ECG) and impact of early invasive strategy in patients with acute coronary syndrome (ACS) without ST-segment elevation. METHODS: Five hundred and forty-five consecutive ACS patients without ST-segment elevation were randomly assigned to early conservative treatment group and early invasive treatment group. The combined cardiovascular events, including cardiac death, nonfatal myocardial infarction, nonfatal heart failure, and re-hospitalization due to recurrent ischemia angina, within 30 days and 6 months were analyzed and the effects of varied ECG changes and different intervention strategies on outcomes of patients were evaluated. RESULTS: The incidences of each and combined cardiovascular events were higher in the patients with ST-segment depression than in those without ST-segment depression. ST-segment depression was one of independent predictive factors for an increase in cardiovascular events within 6 months (OR 3.864, 95% CI: 1.668 approximately 9.451, P < 0.001). Early invasive strategy was associated with a lower rate of re-hospitalization due to recurrent ischemia angina within 30 days and a decreased incidence of combined cardiovascular events within 30 days and 6 months in comparison with the early conservative treatment group (all P < 0.05). Subgroup analysis implied that incidences of combined cardiovascular events within 30 days and 6 months decreased significantly only in patients with ST-segment depression treated with early invasive strategy, and no such benefit was seen in the patients without ST-segment depression. CONCLUSION: ST-segment depression is an effective indicator for identifying those patients with non-ST segment elevation ACS most likely to benefit from early invasive strategy. Early invasive strategy markedly decreases the cardiovascular events in ACS patients with ST-segment depression than early conservative strategy.
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Angina Inestable/fisiopatología , Electrocardiografía , Isquemia Miocárdica/fisiopatología , Enfermedad Aguda , Anciano , Angina Inestable/complicaciones , Angina Inestable/terapia , China , Femenino , Estudios de Seguimiento , Humanos , Masculino , Isquemia Miocárdica/complicaciones , Isquemia Miocárdica/terapia , Pronóstico , Sistema de Registros , Factores de Riesgo , Análisis de Supervivencia , Síndrome , Resultado del TratamientoRESUMEN
OBJECTIVE: To evaluate the value of combining TIMI myocardial perfusion (TMP) grading with sum ST segment resolution (sumSTR) in prediction of the 2-year outcome and heart function in patients with acute myocardial infarction (AMI) after emergency percutaneous intervention (PCI). METHODS: Seventy-seven consecutive patients of AMI with elevated ST segment, 62 males and 15 females, aged 63 +/- 12 (30-91), underwent PCI. TMP grading was used in combination of electrocardiography to calculate the sumSTR so as to evaluate the effect of myocardial reperfusion. The patients with TMP grade 2-3 and sumSTR > or = 30% were included in the group of better perfusion, and those with the TMP grade 0-1 and sumSTR < 30% were included in the group of lower perfusion. The cardiac events, including death, reinfarction, revascularization, angina pectoris, and heart failure were recorded. The left ventricular end-diastolic dimension (LVEDD) and left ventricular ejection fraction (LVEF) were measured by echocardiography 72 hours and 2 years after the PCI. RESULTS: There were 37 patients in the lower perfusion group and 39 patients in the better perfusion group. Cos regression showed that TMP grade 0-1 associated with sumSTR < 30% was an independent factor for 2-year cardiac events (RR = 13.186, 95% CI 2.149 - 80.917, P = 0.005). The LVEDD 2 years after PCI was 60 mm +/- 4 mm, significantly higher than that 72 hours after PCI (53 mm +/- 4 mm. P < 0.01) in the lower perfusion group. The LVEDD increased by 7.1 mm +/- 1.9 mm two years after PCI in the lower perfusion group, significantly more than that in the better perfusion group (1.5 mm +/- 1.2 mm, P < 0.01). The myocardial perfusion after PCI was closely correlated with the extent of heart function improvement 2 years after (chi(2) = 50.58, P < 0.01). CONCLUSION: TMP grading combined with sumSTR helps predict the 2-year outcome and heart function in the patients with AMI after emergency PCI.
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Angioplastia Coronaria con Balón , Circulación Coronaria , Electrocardiografía , Infarto del Miocardio/terapia , Adulto , Anciano , Anciano de 80 o más Años , Angiografía Coronaria , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/fisiopatología , PronósticoRESUMEN
BACKGROUND: Cardiovascular diseases, especially coronary artery disease (CAD), are major causes of death in industrialized countries. Elevated concentrations of plasma homocysteine (Hcy) have been associated with an increased risk of CAD. Increased plasma levels of chemokine, characterized by their ability to induce migration and activation of leukocytes, may contribute to the pathogenesis of CAD. This study was designed to investigate the changes of plasma Hcy, monocyte chemoattractant protein-1 (MCP-1) and oxidative stress markers in acute coronary syndrome patients. METHODS: A total of 149 subjects were divided into four groups: 50 patients with unstable angina, 30 patients with acute myocardial infarction, 20 coronary restenosis patients after percutaneous coronary intervention and 49 healthy control subjects. Plasma levels of Hcy, MCP-1, malondialdehyde and superoxide dismutase were measured. RESULTS: Plasma levels of Hcy and MCP-1 showed significant increases in unstable angina, acute myocardial infarction and restenosis patients compared with control subjects (P < 0.05, respectively). Plasma levels of malondialdehyde were significantly increased in unstable angina and acute myocardial infarction patients when compared with control subjects (P < 0.05, respectively). Plasma superoxide dismutase levels were significantly reduced in acute myocardial infarction patients when compared with control group (P < 0.01). CONCLUSION: Hcy might act as an atherogenic factor through promoting chemokine, reactive oxygen species and oxidized low density lipoprotein production and thereby convert a stable plaque into an unstable potentially occlusive lesion.
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Enfermedad de la Arteria Coronaria/etiología , Enfermedad Coronaria/sangre , Homocisteína/sangre , Estrés Oxidativo , Enfermedad Aguda , Adulto , Anciano , Quimiocina CCL2/sangre , Enfermedad Coronaria/complicaciones , Enfermedad Coronaria/metabolismo , Femenino , Humanos , Lipoproteínas LDL/metabolismo , Masculino , Malondialdehído/sangre , Persona de Mediana Edad , Superóxido Dismutasa/sangreRESUMEN
Reactive oxygen species (ROS) is involved in autoimmune destruction of islet beta cells, which has been proven to be an important underlying pathogenesis for insulin dependent diabetes mellitus (IDDM). Calcitonin gene-related peptide (CGRP) is a widely distributed neuropeptide, which has been found to play an important role in protecting myocytes from ROS. We hypothesized that exogenous CGRP gene administration before the pathogenic stage of insulitis might suppress the production of ROS and provide a hopeful therapeutic intervention for autoimmune diabetes. We performed CGRP gene transfer by injecting naked plasmid directly into skeletal muscles of mice with electroporation enhancement to achieve a continuous expression of CGRP in skeletal muscles, and thereby its secretion into the circulation. The effect of CGRP gene transfer on the pathogenesis of diabetes was studied in autoimmune diabetic mice induced by multiple low dose streptozotocin (MLDS). The CGRP gene therapy decreased morbidity of autoimmune diabetes, and significantly ameliorated hyperglycemia in these mice. CGRP gene transfer inhibited the production of ROS and malondialdehyde (MDA). In addition, it enhanced the activity of catalase (CAT) and superoxide dismutase (SOD) significantly. The data suggest that intramuscular CGRP gene transfer ameliorates autoimmune destruction of islet beta cells, resulting in significant reduction in diabetes incidence of MLDS diabetes mice. CGRP benefits might be mediated at least in part by inhibiting the oxidative stress in islet beta cells of these mice.
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Péptido Relacionado con Gen de Calcitonina/genética , Diabetes Mellitus Tipo 1/prevención & control , Terapia Genética , Especies Reactivas de Oxígeno/metabolismo , Animales , Péptido Relacionado con Gen de Calcitonina/administración & dosificación , Péptido Relacionado con Gen de Calcitonina/uso terapéutico , Diabetes Mellitus Experimental/prevención & control , Técnicas de Transferencia de Gen , Inyecciones Intramusculares , Islotes Pancreáticos/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Páncreas/metabolismo , Superóxido Dismutasa/metabolismo , Transgenes/genéticaRESUMEN
OBJECTIVE: To study the common clinical manifestations of in-stent restenosis. METHODS: Of 431 patients who underwent percutaneous coronary intervention and repeat catheterization between January 1, 1996 and December 31, 2002, 236 consecutive patients with recurrent ischemia and restenosis were identified: 188 patients with (group I) and 48 without (group II) stenting. Patients who developed early acute stent thrombosis were excluded from the study. In the study we compared the clinical manifestations of in-stent restenosis with those of restenosis without stenting. RESULTS: Recurrent clinical ischemia occurred at a mean of 5.3 months in group I and 6.1 months in group II (P > 0.05). Rest angina (Braunwald class 2 and 3, 43% vs 27%, P < 0.05), the combination of rest angina and acute myocardial infarction (43% vs 27%, P < 0.05), and angiographically visible thrombosis (7% vs 0%, P < 0.05) were more frequent in group I than in group II. CONCLUSION: Acute coronary syndromes are the common clinical manifestations of restenosis in patients undergoing percutaneous coronary intervention and occur more frequently in patients with in-stent stenosis than in those with restenosis without stenting.
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Angina de Pecho/diagnóstico , Angioplastia Coronaria con Balón , Reestenosis Coronaria/diagnóstico , Infarto del Miocardio/diagnóstico , Stents , Anciano , Angiografía Coronaria , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: The first-visiting cases of total 272 SARS inpatients admitted in SARS wards in Third Hospital from April 10, 2003 to May 12 were analyzed retrospectively. The clinical characteristics and diagnostic decision for these patients were described. METHODS: The enrollment of inpatients was ruled with two official standards, i.e., 'Clinical Standards for Diagnosis of SARS, Trial Edition' from Health Ministry, and 'Diagnostic Standards for SARS' from Joint Force of Prevention and Therapy for SARS in Beijing, PRC. The present work was based on the first-visiting case records of these SARS inpatients. RESULTS: The characteristics of gender, age, occupation, contagious history and previous therapy were described in SARS inpatients when they visited the outpatient department for SARS in the first time; the clinical symptoms, physical signs, blood WBC counts and X-ray in lungs were also analyzed. In 272 inpatients who were admitted into SARS wards at their first visiting, 145 patients (53.5%) were finally diagnosed as SARS, well as 97 patients (35.7%) were eliminated. CONCLUSION: In the first visiting of the suspectable SARS patients, the contagious history, clinical symptoms, laboratory results and lung X-ray should be studied comprehensively and thoroughly to avoid omitted or mistaken diagnosis. Most final diagnosis came from the revising of the original decision. The advances in SARS virology and immunology may provide more accurate evidences in SARS diagnosis.
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Síndrome Respiratorio Agudo Grave/epidemiología , Adulto , China/epidemiología , Femenino , Humanos , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Radiografía Torácica , Estudios Retrospectivos , Síndrome Respiratorio Agudo Grave/diagnósticoRESUMEN
OBJECTIVE: To study the clinical manifestation, angiographic features, and prognosis of myocardial bridge. METHODS: A retrospective analysis was made on the data of the clinical manifestation, coronary angiography, and prognosis of 35 patients with myocardial bridge, 29 males and 6 females, with an average age of 52.0 +/- 9.5 years, out of 2 871 patients undergoing coronary angiography 1 January 1996 - 20 February 2001. RESULTS: The detection rate of myocardial bridge, mostly in the middle or distal parts of left anterior descending branch and 24 being isolated myocardial bridge, was 1.22% in coronary angiography. There was a significant difference in the extent of diameter stenosis during systolic stage between the group with atherosclerosis (68% +/- 15%, n = 15) and the group without atherosclerosis (54% +/- 14%, n = 20) in the vessel proximal to myocardial bridge (P < 0.01). The systolic diameter stenosis was more severe in the abnormal ECG group (63% +/- 13%, n = 12) than in the normal ECG group (54% +/- 14%, n = 12), P < 0.05. However, the systolic stenosis extent of myocardial bridge in the patients with typical angina pectoris (58% +/- 15%, n = 11) was not significantly different from that in the patients with atypical angina pectoris (54% +/- 15%, n = 13). The systolic stenosis extent of myocardial bridge were 69% +/- 9% (n = 7) and 58% +/- 16% (n = 26) in the patients with and without left ventricular wall hypertrophy respectively (P = 0.09). No malignant event occurred during the follow-up period of 3 - 50 months. CONCLUSION: (1) The more severe the extent of systolic diameter stenosis, the more severe the myocardial ischemia and the more the possibility of abnormal ECG. (2) Myocardial bridge tends to promote or accelerate the atherosclerosis of the vessels proximal to it. (3) Left ventricular wall hypertrophy may promote the formation of myocardial bridge clinically. (4) The prognosis of myocardial bridge is good.
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Enfermedad Coronaria/complicaciones , Angiografía Coronaria , Enfermedad Coronaria/terapia , Femenino , Humanos , Masculino , Pronóstico , Estudios RetrospectivosRESUMEN
BACKGROUND: Many studies have shown that the serum uric acid (SUA) level is one of the cardiovascular risk factors. The aim of the study is to evaluate the relationship between SUA levels and the severity of coronary artery disease (CAD) assessed by angiography and the Syntax score in patients with obstructive CAD. METHODS: Participants who visited our hospital for a coronary angiography, from December 2007 to September 2012, were eligible for this analysis. SUA and other blood parameters after at least 12-hour fast were determined. First, the patients were divided into tertiles according to their Syntax scores (low Syntax score group: Syntax score ≤ 10.0; moderate Syntax score group: 10.0