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Yangsoo Jang

Publications and source records attributed to Yangsoo Jang.

At least 19 recordsLinked to original sources
PubMed2007

Association of the Gly82Ser polymorphism in the receptor for advanced glycation end products (RAGE) gene with circulating levels of soluble RAGE and inflammatory markers in nondiabetic and nonobese Koreans.

We investigated the association between the Gly82Ser (G82S) polymorphism in the receptor for advanced glycation end products (RAGE) gene and circulating levels of soluble RAGE (sRAGE), advanced glycation end products (AGEs), and inflammatory markers in nondiabetic/nonobese Koreans. A total of 1096 men and 580 women aged 30 to 69 years and with body mass index of 18.5 to 29.9 kg/m(2) were recruited. Anthropometrics, lipid profiles, glucose, insulin, insulin resistance (IR), RAGE G82S polymorphism, sRAGE, AGEs, and inflammatory markers were measured. There was a significant association between G82S genotypes and plasma sRAGE concentrations (P < .001). sRAGE concentrations were significantly higher in subjects with the G/G genotype (1038 +/- 33 pg/mL) than in those with the G/S (809 +/- 19 pg/mL) or the S/S (428 +/- 43 pg/mL) genotype. Furthermore, the G82S genotypes in the RAGE gene were associated with serum AGE (P = .033), homeostasis model assessment for insulin resistance (HOMA-IR) (P < .001), plasma tumor necrosis factor alpha (TNF-alpha) (P = .033), serum C-reactive protein (CRP) (P= .002), and urinary excretion of 8-epi-prostaglandin F(2alpha) (P = .028) after adjusting for sex, age, body mass index, cigarette smoking, and alcohol drinking. Subjects with the S/S genotype showed higher levels of serum AGE, HOMA-IR, plasma TNF-alpha, serum CRP, and 8-epi-prostaglandin F(2alpha) than those with the G/G or G/S combination. The sRAGE levels showed a negative relation with high-sensitivity CRP (r = -0.250; P < .001). The AGE concentrations showed a positive relation with TNF-alpha levels (r = 0.398; P < .001). Subjects with homozygosity for the minor S allele (S/S) of the G82S polymorphism had higher risk factors for cardiovascular disease, such as low sRAGE levels, inflammation, oxidative stress, and IR, compared with those bearing at least one G allele.

5' Untranslated Regions↗
PubMed2007

Association of RAGE gene polymorphisms with coronary artery disease in the Korean population.

BACKGROUND AND OBJECTIVES: AGEs (advanced glycation end products)-RAGE (receptor for advanced glycation end products) interaction in vessel wall may lead to inflammation, smooth muscle cell proliferation and extracellular matrix production, culminating in exaggerated intimal hyperplasia and restenosis. We focused on the putative association of five candidate RAGE gene polymorphisms on the risk of coronary artery disease in the Korean population. METHODS: A total of 1555 male patients who underwent coronary angiography were enrolled in the study; 805 patients (mean age: 53.18+/-9.74 years) had normal coronary artery and 750 patients (mean age: 55.73+/-8.31 years) had significant coronary artery disease. Among the coronary artery disease patients, 269 had single-vessel disease (35.87%), 242 had two-vessel disease (32.27%) and 239 had three-vessel disease (31.87%). The genotypes of RAGE were determined by the methods of single base extension with amplifying primers and probes for TaqMan. Genotype analysis was performed on five single nucleotide polymorphisms of the RAGE gene, namely -443T>C, -388T>A, -257G>A, +557G>A and +1704G>T. Analysis for the association with coronary artery disease was performed. RESULTS: Analysis of four single nucleotide polymorphisms, except +557G>A (G82S), with regard to the association with coronary artery disease was not significant. Only the +557 gene allele (G/A) showed significant association with coronary artery disease (coronary artery disease vs. normal; G allele: 0.87 vs. 0.84, A allele: 0.13 vs. 0.16, P=0.0326). The +557G>A (G82S) showed strong tendency of association with coronary artery disease (coronary artery disease vs. normal; GG: 75.2 vs. 69.8%, GA: 23.2 vs. 28.6%, AA: 1.6 vs. 1.6%, P=0.0524). The presence of AA or GA genotype, assuming codominant effect of the A allele, was independently associated with decreased risk of coronary artery disease when controlled for age, body mass index, smoking and diabetes mellitus [odds ratio=0.749 (95% confidence interval, 0.579-0.969), P=0.0280]. Subgroup analysis demonstrated the significant protective effect of AA or GA genotype in nondiabetic patients as well [odds ratio=0.741 (0.570-0.962), P=0.0244]. CONCLUSIONS: The results of this large population study demonstrate that the AA/GA genotypes of the RAGE +557G>A polymorphism are associated with a significantly decreased risk of significant coronary artery disease. Other polymorphisms of RAGE were not significantly associated with the risk of coronary artery disease in this study population.

Asian People↗
PubMed2006

A novel mutation in the SCN5A gene is associated with Brugada syndrome.

Brugada syndrome (BS) is an inherited cardiac disorder associated with a high risk of sudden cardiac death and is caused by mutations in the SCN5A gene encoding the cardiac sodium channel alpha-subunit (Na(v)1.5). The aim of this study was to identify the genetic cause of familial BS and characterize the electrophysiological properties of a novel SCN5A mutation (W1191X). Four families and one patient with BS were screened for SCN5A mutations by PCR and direct sequencing. Wild-type (WT) and mutant Na(v)1.5 channels were expressed in tsA201 cells, and the sodium currents (I(Na)) were analyzed using the whole-cell patch-clamp technique. A novel mutation, W1191X, was identified in a family with BS. Expression of the WT or the mutant channel (Na(v)1.5/W1191X) co-transfected with the beta(1)-subunit in tsA201 cells resulted in a loss of function of Na(v)1.5 channels. While voltage-clamp recordings of the WT channel showed a distinct acceleration of Na(v)1.5 activation and fast inactivation kinetics, the Na(v)1.5/W1191X mutant failed to generate any currents. Co-expression of the WT channel and the mutant channel resulted in a 50% reduction in I(Na). No effect on activation and inactivation were observed with this heterozygous expression. The W1191X mutation is associated with BS and resulted in the loss of function of the cardiac sodium channel.

Adult↗
PubMed2006

Effect of the 252A>G polymorphism of the lymphotoxin-alpha gene on inflammatory markers of response to cigarette smoking in Korean healthy men.

BACKGROUND: The systemic inflammatory response is heightened in smokers. We examined whether the established cardiovascular risk factor, smoking status, might interact with the lymphotoxin-alpha (LTA) gene 252A>G polymorphism in determining concentrations of TNF-alpha and eventually IL-6, adiponectin and CRP downstream in the inflammatory cascade. METHODS: We measured anthropometric parameters, serum lipid profile, glucose, TNF-alpha, IL-6, CRP, adiponectin and urinary excretion of 8-epi PGF2alpha as well as a genotyping for 252A>G polymorphism of LTA in 480 healthy Korean men. RESULTS: After adjustment for age, 208 smokers with an average consumption of 18+/-1 cigarettes/d had higher concentrations of TNF-alpha, IL-6, CRP and urinary excretion of 8-epi PGF2alpha than nonsmokers (n=272). Nonsmokers with G/G had higher TNF-alpha and 8-epi PGF2alpha concentrations than those with A/A or A/G. TNF-alpha concentrations were higher in smokers than nonsmokers of the same genotype. Smokers with G/G showed higher TNF-alpha concentration than those with A/A and had higher IL-6 and urinary 8-epi PGF2alpha concentrations than those with A/G or A/A. Furthermore, smokers carrying the G allele showed lower adiponectin concentrations than those with A/A. There are main effects of genotype and smoking, as well as the smoking-genotype interaction to TNF-alpha concentration. CONCLUSION: Our results suggest that the LTA 252A>G polymorphism may modulate the inflammatory effects and oxidative stress of smoking. The detrimental effect of smoking is most clearly seen in men with G/G, suggesting a genotype-specific interaction with smoking.

Adenosine↗
PubMed2006

Effects of simvastatin on plasma antioxidant status and vitamins in hypercholesterolemic patients.

BACKGROUND: Statins are known to possess antioxidant properties in addition to their cholesterol-lowering effects. However, recent studies have suggested that statins reduce the levels of antioxidant vitamins such as vitamin E and coenzyme Q(10), possibly resulting in impaired left ventricular function. We investigated the effects of simvastatin on the blood lipids, LDL oxidation and plasma antioxidant status, and whether these effects were associated with changes in plasma antioxidant vitamin levels. METHODS: Simvastatin (20-40 mg/day) was administered for 8 weeks in seventy-six hypercholesterolemic patients. We measured plasma lipids, oxidized LDL, total radical trapping antioxidant potential (TRAP) and plasma antioxidant vitamin levels at baseline and after 8 weeks of simvastatin administration. RESULTS: Simvastatin significantly lowered serum levels of total cholesterol and LDL-cholesterol by 30.1% and 41.9%, respectively. A significant reduction in oxidized LDL levels (p<0.0001) and improvement in plasma antioxidant status as measured by TRAP (p<0.05) after the 8-week simvastatin treatment were observed. Regarding the effects of simvastatin on plasma antioxidant vitamin levels, there were significant increases in the levels of lipid-corrected retinol (p<0.001), alpha-tocopherol (p<0.001) and gamma-tocopherol (p<0.005) after the 8-week simvastatin treatment. Lipid-corrected levels of coenzyme Q10 and carotenoids remained unchanged after simvastatin treatment. CONCLUSIONS: Our results show that simvastatin reduced blood lipids and circulating oxidized LDL, and improved plasma antioxidant status without altering the antioxidant vitamin system. These data indicate that simvastatin not only decreases blood lipids and circulating oxidized LDL but also increases lipid corrected levels of antioxidant vitamins and may improve plasma antioxidant status synergizing with the biological effects of antioxidants.

Adult↗
PubMed2006

Association of RAGE gene polymorphisms with in-stent restenosis in non-diabetic Korean population.

BACKGROUND: Interaction between advanced glycosylation end products (AGEs) and receptor for AGEs (RAGE) in vessel wall may lead to inflammation, smooth muscle cell proliferation, and extracellular matrix production, culminating in exaggerated intimal hyperplasia and restenosis. We investigated the possibility that single nucleotide polymorphisms of the genes encoding RAGE are associated with in-stent restenosis after coronary stenting. METHODS: Our study included 334 consecutive non-diabetic male patients with symptomatic coronary artery disease who underwent bare metal stent implantation. Follow-up angiography was performed in 297 patients (88.9%), 6 months after intervention. We screened -1106T-->C, -443T-->C, -388T-->A, -257G-->A, +557G-->A and +1704G-->T RAGE polymorphisms in these patients. Genotyping was performed by single base extension with amplifying primers and probes for TaqMan. RESULTS: A total of 355 target lesions were evaluated, in 297 patients. There was no significant association of the -1106T-->C, -443T-->C, -388T-->A, -257G-->A, +557G-->A or +1704G-->T polymorphisms with in-stent restenosis after coronary artery stenting. We did not observe a significant difference between the genotype distributions and the rates of angiographic restenosis between the polymorphisms. In a multivariate analysis of angiographic restenosis, we examined the possible influence of the baseline, lesion-related, and procedural variables. After adjustment for these potentially confounding factors, the multivariate analysis did not reveal an association of polymorphism with angiographic restenosis. CONCLUSION: Our observation suggests that the RAGE gene polymorphism is not associated with in-stent restenosis after coronary artery stenting in non-diabetic patients in the Korean population.

Angioplasty, Balloon, Coronary↗
PubMed2006

PPARgamma activation induces CD36 expression and stimulates foam cell like changes in rVSMCs.

The purpose of the present study was to determine the role of peroxisome proliferator-activated receptor gamma (PPARgamma) activation in smooth muscle cell (SMC) derived form cell formation. Wild and mutant type PPARgamma were delivered by adenovirus then activated with troglitazone. The result of Oil Red O staining and FACS analysis showed that PPARgamma activation induced lipid accumulation in rVSMCs. Furthermore, PPARgamma activation reduced SMC marker genes such as alpha-actin while induced adipocyte differentiation marker genes and lipid metabolism-related genes as evidenced by RT-PCR and fluorescent immunocytochemistry. All these data demonstrate that PPARgamma activation can drive foam cell like change in rVSMCs. Our results strongly suggest that PPARgamma expression induces CD36 expression and adipocyte differentiation gene activation in the process of atherosclerosis and might be one of the crucial events in SMC derived foam cell formation.

ATP Binding Cassette Transporter 1↗
PubMed2006

Cordycepin inhibits lipopolysaccharide-induced inflammation by the suppression of NF-kappaB through Akt and p38 inhibition in RAW 264.7 macrophage cells.

Cordyceps militaris, a caterpillar-grown traditional medicinal mushroom, produces an important bioactive compound, cordycepin (3'-deoxyadenosine). Cordycepin is reported to possess many pharmacological activities including immunological stimulating, anti-cancer, anti-virus and anti-infection activities. The molecular mechanisms of cordycepin on pharmacological and biochemical actions of macrophages in inflammation have not been clearly elucidated yet. In the present study, we tested the role of cordycepin on the anti-inflammation cascades in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. In LPS-activated macrophage, nitric oxide (NO) production was inhibited by butanol fraction of C. militaris and the major component of C. militaris butanol faction was identified as cordycepin by high performance liquid chromatography. To investigate the mechanism by which cordycepin inhibits NO production and inducible nitric oxide synthase (iNOS) expression, we examined the activation of Akt and MAP kinases in LPS-activated macrophage. Cordycepin markedly inhibited the phosphorylation of Akt and p38 in dose-dependent manners in LPS-activated macrophage. Moreover, cordycepin suppressed tumor necrosis factor (TNF-alpha) expression, IkappaB alpha phosphorylation, and translocation of nuclear factor-kappaB (NF-kappaB). The expressions of cycloxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) were significantly decreased in RAW 264.7 cell by cordycepin. Taken together, these results suggest that cordycepin inhibits the production of NO production by down-regulation of iNOS and COX-2 gene expression via the suppression of NF-kappaB activation, Akt and p38 phosphorylation. Thus, cordycepin may provide a potential therapeutic approach for inflammation-associated disorders.

Animals↗
PubMed2006

The Val279Phe variant of the lipoprotein-associated phospholipase A2 gene is associated with catalytic activities and cardiovascular disease in Korean men.

CONTEXT AND OBJECTIVE: It is unclear whether lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) exerts a pro- or antiatherogenic effect on cardiovascular disease (CVD). We investigated the association between Lp-PLA(2) variant (V279F and A379V) and CVD in Korean men. DESIGN: CVD patients (n = 532) and healthy controls (n = 670) were genotyped for the Lp-PLA(2) polymorphism (V279F and A379V). MAIN OUTCOME MEASURES: We calculated odds ratio (OR) on CVD risk and measured anthropometries, lipid profiles, low-density lipoprotein (LDL) particle size, oxidized LDL, lipid peroxides, and Lp-PLA(2) activity. RESULTS: The presence of the 279F allele was associated with a lower risk of CVD [OR 0.646 (95% confidence interval 0.490-0.850), P = 0.002], and the association still remained after adjustments for age, body mass index, waist circumference, waist to hip ratio, cigarette smoking, and alcohol consumption [OR 0.683 (95% confidence interval 0.512-0.911), P = 0.009]. Lp-PLA(2) activity was lower in CVD patients taking a lipid-lowering drug (31%), those not taking a lipid-lowering drug (26%), and control subjects (23%) with the V/F genotype, compared with those with the V/V genotype. Subjects with the F/F genotype in controls and two CVD patients groups showed no appreciable enzymatic activity. Control subjects with the V/F genotype had larger LDL particle size than those with the V/V genotype. In addition, control subjects carrying the F allele showed lower malondialdehyde concentrations. On the other hand, we found no significant relationship between A379V genotype and CVD risk. CONCLUSIONS: The association of the F279 loss of function variant with the reduced risk of CVD supports the concept that Lp-PLA(2) plays a proatherogenic and causative role in CVD.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed2006

Significant association of C-reactive protein with arterial stiffness in treated non-diabetic hypertensive patients.

C-reactive protein (CRP) has been known to be associated with vascular inflammation and hypertension. Pulse wave velocity (PWV) increases according to the degree of the arterial stiffness in hypertension patients. Therefore, PWV may be correlated with CRP levels in treated hypertensive patients, irrespective of medication. We sought to determine whether there is a correlation between hsCRP and arterial stiffness in non-diabetic treated hypertensive patients, independent of cardiovascular risk factor. This study consisted of 424 non-diabetic patients at least 45-years-old who were being treated for hypertension. At the time of enrollment, the patients underwent a baseline laboratory assessment of C-reactive protein levels and pulse wave velocity (PWV). Heart to femoral PWV (hfPWV) and brachial to ankle PWV (baPWV) were used as a marker of arterial stiffness. Subjects were categorized according to tertiles of hsCRP level [Group 1: first tertile (0.20-0.46 mg/L), Group 2: second tertile (0.47-1.15 mg/L), Group 3: third tertile (1.17-9.71 mg/L)]. Group 1 consisted of 141 patients (mean age 58+/-8 years), Group 2 had 142 patients (mean age 60+/-9 years) and Group 3 had 141 patients (mean age 61+/-8 years). The hfPWV and baPWV increased significantly along with the hsCRP level. Group 1, Group 2 and Group 3 demonstrated hfPWV and baPWV of 965+/-199 and 1438+/-246, 975+/-174 and 1487+/-258 and 1043+/-215 and 1566+/-252 cm/s, respectively (p<0.01). The hfPWV also showed a strong correlation with baPWV (r=0.698, p<0.001). The hsCRP level was independently associated with arterial stiffness (hfPWV: R(2)=0.273, p<0.001; baPWV: R(2)=0.284, p=0.001) after controlling for age, body mass index, systolic blood pressure (BP), heart rate, gender, HDL-cholesterol, triglyceride, glucose level and medications. In conclusion, hsCRP was associated with arterial stiffness, independent of age, systolic BP, gender, heart rate, glucose, lipid profiles and medications in treated hypertension. Therefore, hsCRP could be a useful marker of arterial stiffness in treated hypertension patients and a possible target for arterial inflammation in hypertension.

Aged↗
PubMed2006

Troglitazone inhibits endothelial cell proliferation through suppression of casein kinase 2 activity.

Troglitazone, an agonist of peroxisome proliferator activated receptor gamma (PPARgamma), has been reported to inhibit endothelial cell proliferation by suppressing Akt activation. Recently, it has been also proposed that phosphatase and tensin homolog deleted from chromosome 10 (PTEN) plays an important role in such effect of troglitazone. However, the mechanism of how troglitazone regulates PTEN remains to be elucidated. We therefore investigated the effects of troglitazone on casein kinase 2 (CK2), which is known to negatively regulate PTEN activity. Troglitazone significantly inhibited serum-induced proliferation of HUVEC in a concentration dependent manner. Serum-induced Akt and its downstream signaling pathway activation was attenuated by troglitazone (10 microM) pretreatment. The phosphorylation of PTEN, which was directly related to Akt activation, was decreased with troglitazone pretreatment and was inversely proportional to CK2 activity. DRB, a CK2 inhibitor, also showed effects similar to that of troglitazone on Akt and its downstream signaling molecules. In conclusion, our results suggest that troglitazone inhibits proliferation of HUVECs through suppression of CK2 activity rendering PTEN to remain activated, and this effect of troglitazone in HUVECs seems to be PPARgamma independent.

Casein Kinase II↗
PubMed2006

The applicability of the Asian modified criteria of the metabolic syndrome in the Korean population.

BACKGROUND: We compared the metabolic profiles and risk of coronary artery disease (CAD) in Koreans with non-diabetic metabolic syndrome (MetS). [We applied four criteria of MetS: the NCEP criteria, the Asian modified NCEP (a-NCEP) criteria, the WHO criteria and the Asian modified WHO (a-WHO).] METHODS: The study group composed of 2724 subjects enrolled in the cardiovascular genome center. There were 728 patients with significant CAD. The different criteria of the MetS were applied for the study population. RESULTS: Among the 2724 participants, 522 (19.2%) met the NCEP criteria, 796 (29.2%) met the a-NCEP criteria, 361 (13.3%) met the WHO criteria and 576 (21.1%) met the a-WHO criteria. The clinical parameters, lipid profile, apoA1 and apoB level were not different between the participants classified as MetS by using the different criteria. The odds ratio for CAD prediction were not significantly different according to the metabolic criteria (odd ratio: 1.755 [95% CI: 1.423-2.163] in NCEP criteria, 2.120 [1.763-2.549] in a-NCEP criteria, 1.854 [1.466-2.343] in WHO criteria, 2.205 [1.810-2.687] in a-WHO criteria). The serum level of apoA1 and apoB showed strong correlations with MetS classified by all criteria and the HOMA index and insulin level showed better correlations with WHO-MetS criteria. CONCLUSIONS: All the MetS criteria showed similar metabolic profiles and all four criteria had similar predictive value for CAD. Conventional MetS criteria, applied to the non-diabetic Asian population, may underestimate the population at risk. Our data suggests that the Asian modified criteria will decrease the risk for underdiagnosis while demonstrating similar metabolic profiles and CAD risk compared to the conventional criteria.

Coronary Artery Disease↗
PubMed2006

Plasma adiponectin is related to other cardiovascular risk factors in nondiabetic Korean men with CAD, independent of adiposity and cigarette smoking: cross-sectional analysis.

BACKGROUND: Circulating adiponectins have multiple protective roles as anti-diabetic, anti-atherosclerotic, and anti-inflammatory factors. We examined the relationship between plasma adiponectin concentration and other cardiovascular risk in nondiabetic coronary artery disease (CAD) men and the relationship can be maintained even after adjusted for major environmental factors that contribute to adiponectin concentrations. METHODS: Nondiabetic CAD men (n=613) were 31-70 y and had body mass index (BMI) of 18.5-29.9 kg/m2. RESULTS: Circulating adiponectins positively correlated with age and negatively with BMI, waist circumference and % body fat (p-values of all <0.001). Plasma adiponectin concentrations were higher in never-smokers (5.07+/-0.30 microg/ml) than current (4.15+/-0.12 microg/ml) and ex-smokers (3.75+/-0.20 microg/ml) both before and after adjusted for age and adiposity (p=0.002 and p=0.008, respectively), however they were not significantly different according to alcohol drinking status. After adjusted for age, adiposity and cigarette smoking, plasma adiponectin still have positive correlations with HDL cholesterol, apolipoprotein AI and LDL particle size, and inversely with fasting triglyceride, atherogenic index, insulin resistance and C-reactive protein (CRP). However there was no significant relationships between adiponectin and apolipoprotein B, total cholesterol or LDL cholesterol. In subset analysis by tertile adiponectin concentrations (lowest: <2.92, moderate: 2.92 or=4.75 microg/ml), 'moderate' and 'highest' adiponectin groups had lower triglyceride (p<0.001), lower atherogenic index (p=0.001), lower fasting insulin (p=0.004), lower insulin resistance (p=0.001), lower CRP (p=0.001), higher HDL cholesterol (p<0.001), higher apolipoprotein AI (p=0.005) and higher LDL particle size (p<0.001) as compared with 'lowest' adiponectin group when adjusted for age, adiposity and cigarette smoking. Platelets were lower in 'highest' adiponectin groups as compared with 'lowest' and 'moderate' adiponectin group after the adjustment. However, there was no significant difference in total cholesterol (p=0.145), LDL cholesterol (p=0.145), apolipoprotein B (p=0.222) and fasting glucose (p=0.157). CONCLUSION: An increase of adiponectin concentrations or the maintenance of higher concentration may be negatively associated with cardiovascular risk factors in nondiabetic CAD male patients, independent of adiposity and smoking status.

Adiponectin↗
PubMed2006

Allopurinol modulates reactive oxygen species generation and Ca2+ overload in ischemia-reperfused heart and hypoxia-reoxygenated cardiomyocytes.

Myocardial oxidative stress and Ca2+ overload induced by ischemia-reperfusion may be involved in the development and progression of myocardial dysfunction in heart failure. Xanthine oxidase, which is capable of producing reactive oxygen species, is considered as a culprit regarding ischemia-reperfusion injury of cardiomyocytes. Even though inhibition of xanthine oxidase by allopurinol in failing hearts improves cardiac performance, the regulatory mechanisms are not known in detail. We therefore hypothesized that allopurinol may prevent the xanthine oxidase-induced reactive oxygen species production and Ca2+ overload, leading to decreased calcium-responsive signaling in myocardial dysfunction. Allopurinol reversed the increased xanthine oxidase activity in ischemia-reperfusion injury of neonatal rat hearts. Hypoxia-reoxygenation injury, which simulates ischemia-reperfusion injury, of neonatal rat cardiomyocytes resulted in activation of xanthine oxidase relative to that of the control, indicating that intracellular xanthine oxidase exists in neonatal rat cardiomyocytes and that hypoxia-reoxygenation induces xanthine oxidase activity. Allopurinol (10 microM) treatment suppressed xanthine oxidase activity induced by hypoxia-reoxygenation injury and the production of reactive oxygen species. Allopurinol also decreased the concentration of intracellular Ca2+ increased by enhanced xanthine oxidase activity. Enhanced xanthine oxidase activity resulted in decreased expression of protein kinase C and sarcoendoplasmic reticulum calcium ATPase and increased the phosphorylation of extracellular signal-regulated protein kinase and p38 kinase. Xanthine oxidase activity was increased in both ischemia-reperfusion-injured rat hearts and hypoxia-reoxygenation-injured cardiomyocytes, leading to reactive oxygen species production and intracellular Ca2+ overload through mechanisms involving p38 kinase and extracellular signal-regulated protein kinase (ERK) via sarcoendoplasmic reticulum calcium ATPase (SERCA) and protein kinase C (PKC). Xanthine oxidase inhibition with allopurinol modulates reactive oxygen species production and intracellular Ca2+ overload in hypoxia-reoxygenation-injured neonatal rat cardiomyocytes.

Allopurinol↗
PubMed2006

Insulin resistance is associated with hypertensive response to exercise in non-diabetic hypertensive patients.

AIM: Insulin resistance is associated with increased sympathetic activity and elevated angiotensin II which may contribute to the excessive increase in arterial blood pressure during exercise. In this study, we hypothesized that increased insulin resistance will be significantly associated with hypertensive response to exercise (HRE) in non-diabetic hypertensive patients. METHOD: Two hundred seventy-five hypertensive patients were included in this study. HOMA-IR index using serum fasting glucose and insulin was calculated for insulin resistance. There were 79 patients with hypertensive response (age 56.1+/-9.4 years) and 196 patients without hypertensive response (age 53.9+/-8.9 years). RESULTS: Insulin resistance, assessed by HOMA index, was significantly higher in hypertensive response group as compared to control (HOMA=2.60+/-1.54 versus 1.76+/-0.86, P<0.001). HOMA was an independent predictor of HRE when controlled for age, sex, BMI and baseline SBP (odds ratio=2.008, P<0.001). Also, HOMA was significantly correlated with the magnitude of SBP elevation controlled for age, sex, BMI and baseline SBP as well (beta=0.293, P<0.001). In conclusion, this study shows that insulin resistance is a significant determinant of hypertensive response to exercise. Further studies to determine the prognostic significance of this finding is warranted.

Adult↗
PubMed2006

Comparison of sirolimus-eluting stent, paclitaxel-eluting stent, and bare metal stent in the treatment of long coronary lesions.

OBJECTIVE: This study compared the efficacy of the sirolimus-eluting stent (SES), the paclitaxel-eluting stent (PES), and the bare metal stent (BMS) for long coronary lesions. BACKGROUND: The outcome of drug-eluting stent (DES) implantation in long coronary lesions remains unclear. METHODS: The study involved 527 patients with de novo long coronary lesions (> or = 24 mm), which were treated with long (> or = 28 mm) SESs (223 lesions), PESs (194 lesions), or BMSs (201 lesions). RESULTS: Lesions in the SES (36.0 +/- 14.9 mm, P < 0.001) and PES (36.3 +/- 14.5 mm, P < 0.001) groups were longer than those in the BMS group (32.0 +/- 12.3 mm), meaning the two DES groups had longer stented segments than did the BMS group. Six-month angiographic follow-up showed the SES (9.3%, P < 0.001) and PES (21.3%, P < 0.001) groups had lower in-segment restenosis rates than that of the BMS group (42.5%). The rate of major adverse cardiac events (MACE) including death, myocardial infarction, and target lesion revascularization at 9 months was higher in the BMS group (26.6%) than that in the SES (13.0%, P < 0.001) and PES (15.7%, P < 0.001) groups. Posthoc analysis of the two DES groups showed that the in-segment restenosis rate was lower for the SES than that for the PES group (P = 0.002), while the MACE rate was similar. CONCLUSIONS: The use of DESs for long coronary lesions appears to be safe and more effective than the use of BMSs in terms of restenosis and adverse clinical events. SES use was associated with lower late luminal loss and a lower angiographic restenosis rate compared with PES use.

Analysis of Variance↗
PubMed2006

Systemic immunosuppressive therapy inhibits in-stent restenosis in patients with renal allograft.

BACKGROUND: Cyclosporine is used routinely for prophylaxis for renal allograft rejection. In experimental animal studies, cyclosporine had been shown to inhibit smooth muscle cell proliferation during the arterial response to injury. We investigated whether systemic immunosuppression may inhibit in-stent restenosis in renal transplant patients undergoing coronary stenting. METHODS: From 1993 to 2003, 33 renal transplant patients with 45 coronary lesions and 37 dialysis patients with 52 lesions underwent coronary stenting using bare metal stents at our center. We followed all patients clinically for a mean period of 37 +/- 31 months and 40 patients angiographically at 14 +/- 15 months after coronary intervention. Cyclosporine was combined with corticosteroids in 32 patients and one patient received tacrolimus instead of cyclosporine. RESULTS: The baseline clinical and angiographical characteristics were similar and the success rate of the procedure was 100% in both groups. In renal transplant group, the mean dose of cyclosporine was 192.5 +/- 68 mg/day and the blood cyclosporine level at the time of procedure was 152.9 +/- 51.5 ng/mL. The rate of in-stent restenosis was 7.1% in renal transplant group and 57.1% in dialysis group (P < 0.0001). The mean late loss was 0.47 +/- 0.57 mm in renal transplant group when compared with 1.51 +/- 1.09 mm in dialysis group (P = 0.004). The overall rate of major adverse cardiac events (MACEs) was 6.1% in renal transplant group and 35.1% in dialysis group (P < 0.0001). CONCLUSIONS: Renal transplant patients receiving combined immunosuppressive agents showed markedly low rates of in-stent restenosis and MACE after coronary revascularization with stent. We consider that this result may be related to the ability of combined immunosuppressive therapy to inhibit inflammatory reaction and vascular smooth muscle cell proliferation induced by coronary stenting.

Coronary Angiography↗