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Jaw-Wen Chen

Publications and source records attributed to Jaw-Wen Chen.

At least 19 recordsLinked to original sources
PubMed2007

Pravastatin induces thrombomodulin expression in TNFalpha-treated human aortic endothelial cells by inhibiting Rac1 and Cdc42 translocation and activity.

Expression of functionally active thrombomodulin (TM) on the luminal surface of endothelial cells is critical for vascular thromboresistance. The 3-hydroxyl-3-methyl coenzyme A reductase inhibitor, pravastatin, can protect the vasculature in a manner that is independent of its lipid-lowering activity. We examined the effect of pravastatin on TM expression by human aortic endothelial cells (HAECs) with subsequent tumor necrosis factor alpha (TNFalpha) stimulation and investigated the signaling pathways involved. TNFalpha treatment attenuated TM expression in HAECs in a time-dependent manner. Pravastatin upregulated TM levels in TNFalpha-treated HAECs. Specific inhibition of geranylgeranyltransferase-I or the Rho family by GGTI-286 or TcdB, respectively, enhanced TM expression in TNFalpha-treated HAECs, whereas MAP kinase inhibitors, inactivation of Rho by Clostridium botulinum C3 exoenzyme, or the Rho kinase inhibitor, Y-27632, had no effect. In TNFalpha-treated HAECs, pravastatin inhibited Rac1 and Cdc42 activation and their translocation to the cell membrane. Blocking the transcriptional activation of NF-kappaB prevented the TNFalpha-induced downregulation of TM. The pravastatin-induced increase in TM expression in TNFalpha-treated HAECs was mediated through inhibition of NF-kappaB activation. Pravastatin regulates TM expression by inhibiting the activation of the Rho family proteins, Rac1 and Cdc42, and the transcription factor, NF-kappaB. The increase in endothelial TM activity in response to pravastatin constitutes a novel pleiotropic (nonlipid-related) effect of this commonly used compound and may be of clinical significance in disorders in which deficient endothelial TM plays a pathophysiological role.

Amides↗
PubMed2007

Salvianolic acid B attenuates MMP-2 and MMP-9 expression in vivo in apolipoprotein-E-deficient mouse aorta and in vitro in LPS-treated human aortic smooth muscle cells.

Salvianolic acid B (Sal B), a water-soluble antioxidant derived from a Chinese medicinal herb, is believed to have multiple therapeutic and preventive against human vascular diseases, including atherosclerosis and restenosis. To elucidate the underlying cellular mechanisms, we produced hypercholesterolemia by feeding apo-E-deficient mice a 0.15% cholesterol diet and inflammation in human aortic smooth muscle cells (HASMCs) with the endotoxin lipopolysaccharide (LPS), focusing on the metallopreteinases MMP-2 and MMP-9, the relevant signal transduction pathways and the effects of Sal B. Immunohistochemical analyses indicated apo-E-deficient mice fed a 0.15% cholesterol diet for 12 weeks exhibited thickened intima and elevated levels of MMP-2 and MMP-9 in aortic sections, both of which were attenuated by 0.3% Sal B dietary supplement. Western blotting and zymography analyses indicated that unstimulated HASMCs exhibited basal levels of protein and activity levels for MMP-2 and barely detectable levels for MMP-9, both of which were markedly upregulated by LPS, which also induced cell migration. Sal B significantly attenuated upregulations of both MMPs as well as the LPS-induced cell migration through the inactivation of MMP-2 and MMP-9 protein synthesis as well as the downregulation of the extracellular-signal-regulated kinase 1/2 (ERK1/2) and c-Jun NH(2)-terminal kinase (JNK). These results demonstrate that Sal B has anti-migration properties on smooth muscle cells and may explain its anti-atherosclerotic properties. This novel mechanism of action of Sal B, in addition to its previously reported inhibition of LDL oxidation, may help explain its efficacy in the treatment of atherosclerosis.

Animals↗
PubMed2006

Increased endothelial monocyte adhesiveness is related to clinical outcomes in chronic heart failure.

BACKGROUND: Vascular inflammation and endothelial dysfunction are evident in patients with chronic heart failure (CHF). We hypothesized that circulating peripheral blood mononuclear cells (PBMCs) may be activated and the resultant increased endothelial monocyte adhesion may be functionally and pathophysiologically relevant in CHF. In the present study, we investigated the clinical significance of the activity of PBMCs in patients with CHF. METHODS: PBMCs were isolated from 34 CHF patients, from 10 healthy volunteers (normal control group) and from 17 patients admitted for investigation of suspected coronary artery disease (disease control group). In each patient, the adhesiveness of PBMCs to cultured human aortic endothelial cells (HAECs) with or without tumor necrosis factor-alpha (TNF-alpha) stimulation was determined. Major adverse cardiac events (death, heart transplantation or hospitalization with worsening heart failure) were determined in the 34 CHF patients during a median follow-up period of 182 days. RESULTS: Compared with those from both control groups and from mild CHF patients, PBMCs isolated from severe CHF patients adhered more to the HAECs. The endothelial adhesiveness of PBMCs correlated positively with the circulating levels of CAMs and can supply prognostic information in CHF patients. The difference between event-free curves based on the median levels of endothelial-PBMC adhesion was significant (log rank test, p=0.0139). CONCLUSIONS: Endothelial adhesiveness of PBMCs is increased and correlated to clinical outcomes, and may be pathophysiologically relevant to the progression of CHF.

Aged↗
PubMed2006

Endotoxin induces toll-like receptor 4 expression in vascular smooth muscle cells via NADPH oxidase activation and mitogen-activated protein kinase signaling pathways.

OBJECTIVE: Toll-like receptor 4 (TLR4) plays a major role mediating endotoxin-induced cellular inflammation and regulates vascular smooth muscle cell (VSMC) proliferation, which is related to atherogenesis and restenosis. This study was conducted to investigate the mechanisms involved in lipopolysaccharide (LPS)-induced TLR4 expression in VSMCs. METHODS AND RESULTS: Stimulation of human aortic smooth muscle cells (HASMCs) with LPS significantly increased TLR4 expression. The increase was regulated by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (including the activation of subunits p47(phox) and Rac1), which mediates the production of reactive oxygen species and the activation of intracellular mitogen-activated protein kinase signaling pathways. Treatment with polyethylene-glycol-conjugated superoxide dismutase, N-acetylcysteine (NAC), diphenylene iodonium (DPI), or apocynin significantly decreased LPS-induced TLR4 expression. An actinomycin D chase experiment showed that LPS increased the half-life of TLR4 mRNA. Inhibition of NADPH oxidase activity by DPI, apocynin, or NAC significantly decreased TLR4 mRNA stability, as did the knock-down of RAC1 gene expression by RNA interference. We also demonstrated in an animal model that LPS administration led to a significant elevation of balloon-injury-induced neointimal hyperplasia, and of TLR4 expression, in rabbit aorta. CONCLUSIONS: These findings suggest that NADPH oxidase activation, mRNA stabilization, and MAPK signaling pathways play critical roles in LPS-enhanced TLR4 expression in HASMCs, which contributes to vascular inflammation and cardiovascular disorders.

Acetophenones↗
PubMed2006

The role of human antigen R, an RNA-binding protein, in mediating the stabilization of toll-like receptor 4 mRNA induced by endotoxin: a novel mechanism involved in vascular inflammation.

OBJECTIVE: Lipopolysaccharide (LPS) interacts with toll-like receptor 4 (TLR4) and induces proliferation of vascular smooth muscle cells (VSMCs) which plays a causal role in atherogenesis. The role of TLR4 expression and regulation in LPS-stimulated VSMCs remains unclear. TLR4 mRNAs often contain AU-rich elements (AREs) in their 3' untranslated regions (3'UTR) which have a high affinity for RNA-binding proteins. It is not know whether the RNA-binding protein, human antigen R (HuR), regulates TLR4 expression in human aortic smooth muscle cells (HASMCs). METHODS AND RESULTS: Stimulation of HASMCs with LPS significantly increased the cytosolic HuR level in vitro. Immunoprecipitation and RT-PCR demonstrated that LPS markedly increased the interaction of HuR and 3'UTR of TLR4 mRNA. The reporter plasmid, which contains the 3'UTR of TLR4 mRNA, significantly increased luciferase reporter gene expression in LPS-induced HASMCs. These data suggest that the 3'UTR of TLR4 mRNA confers LPS responsiveness and that HuR modulates 3'UTR-mediated gene expression. Knock-down of HuR inhibited LPS-induced TLR4 mRNA stability in HASMCs and luciferase reporter gene expression in CMV-Luciferase-TLR4 3'UTR-transfected HASMCs. In addition, inhibition of NADPH oxidase activity by diphenylene iodonium, knock-down of Rac1 gene expression by siRNA, and decrease of p38 MAPK activity by SB203580 significantly decreased the cytosolic HuR level, which mediates TLR4 mRNA stability. CONCLUSIONS: Activation of NADPH oxidase and the MAPK-signaling pathway contribute to HuR-mediated stabilization of TLR4 mRNA induced by LPS in HASMCs. In the balloon injured rabbit aorta model, systemic inflammation induced by LPS caused intimal hyperplasia and increased TLR4 and HuR expression.

Animals↗
PubMed2006

Salvianolic acid B attenuates cyclooxygenase-2 expression in vitro in LPS-treated human aortic smooth muscle cells and in vivo in the apolipoprotein-E-deficient mouse aorta.

Inflammation plays an essential role in atherosclerosis and post-angioplasty restenosis and the synthesis and release of inflammatory cytokines from vascular smooth muscle cells is an important contributor to these pathologies. It is assumed that drugs that prevent the overproduction of inflammatory cytokines may inhibit cardiovascular disorders. In the present study, the effects of a water-soluble antioxidant, salvianolic acid B (Sal B), derived from a Chinese herb, on the expression of cyclooxygenase (COX) in lipopolysaccharide (LPS)-treated human aortic smooth muscle cells (HASMCs) and in the aortas of cholesterol-fed apoE deficient mice were investigated. In unstimulated HASMCs, COX-2 mRNA and protein were almost undetectable, but were strongly upregulated in response to LPS. In contrast, HASMCs with or without LPS treatment showed constitutive expression of COX-1 mRNA and protein. The activation of COX-2 protein synthesis in LPS-stimulated HASMCs was shown to involve the activation of the extracellular-signal-regulated kinase 1/2 (ERK1/2), c-Jun NH(2)-terminal kinase (JNK), and p38 mitogen-activated protein kinase pathway. Incubation of HASMCs with Sal B before LPS stimulation resulted in pronounced downregulation of COX-2 expression. Sal B treatment suppressed ERK1/2 and JNK phosphorylation and attenuated the increase in prostaglandin E(2) production and NADPH oxidase activity in LPS-treated HASMCs. When apoE-deficient mice were fed a 0.15% cholesterol diet with or without supplementation with 0.3% Sal B for 12 weeks, the intima/media area ratio in the thoracic aortas was significantly reduced in the Sal B group (0.010 +/- 0.009%) compared to the apoE-deficient group (0.114 +/- 0.043%) and there was a significant reduction in COX-2 protein expression in the thickened intima. These results demonstrate that Sal B has anti-inflammatory properties and may explain its anti-atherosclerotic properties. This new mechanism of action of Sal B, in addition to its previously reported inhibition of LDL oxidation, may help explain its efficacy in the treatment of atherosclerosis.

Animals↗
PubMed2006

Decreased heparin cofactor II activity is associated with impaired endothelial function determined by brachial ultrasonography and predicts cardiovascular events.

BACKGROUND: Heparin cofactor II (HCII) could inactivate thrombin after binding to dermatan sulfate at injured arterial walls, and has been shown to be a novel and independent antiatherosclerotic factor. However, the relation between plasma HCII activity and peripheral vascular endothelial function remains unclear. METHODS: A total of 199 patients (mean age, 63+/-14 years) were enrolled and followed up for a median period of 24 months. Endothelial function was assessed using brachial ultrasonography to determine endothelium dependent flow-mediated vasodilation (FMD). Cox regression analyses were conducted for the 199 subjects, with cardiovascular events being defined as myocardial infarction (MI), percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), ischemic stroke, and peripheral artery revascularization. RESULTS: A total of 31 patients (16%) had cardiovascular events. Patients with cardiovascular events had significantly lower HCII activity (112+/-34 versus 127+/-34%, p=0.027) and lower antithrombin III (ATIII) activity (82+/-12 versus 88+/-13%, p=0.014) than those without events. By multivariate analysis, age (p=0.012), hsCRP (p=0.020) and HCII activity (p=0.035) were correlated with FMD. Kaplan-Meier analysis was performed and showed plasma HCII (p=0.036) and ATIII activities (p=0.005) were predictors of cardiovascular events. By Cox regression analysis, plasma HCII activity (p=0.026) could be an independent predictor of future cardiovascular events, but not ATIII. CONCLUSIONS: The present study demonstrates that plasma HCII activity is positively correlated with endothelial vasodilator function. Furthermore, plasma HCII activity could be a predictor of future cardiovascular events in patients with suspected coronary artery disease, suggesting its role in atherosclerosis.

Aged↗
PubMed2006

Superoxide dismutase and catalase inhibit oxidized low-density lipoprotein-induced human aortic smooth muscle cell proliferation: role of cell-cycle regulation, mitogen-activated protein kinases, and transcription factors.

Several antioxidant enzymes, including copper, zinc-superoxide dismutase (Cu, Zn-SOD) and catalase, have been suggested to be protective against the proliferation of vascular smooth muscle cells exposed to oxidative stress. In the present study, we investigated effects of Cu, Zn-SOD and/or catalase on oxLDL-induced proliferation of, and intracellular signaling in, human aortic smooth muscle cells (HASMCs). HASMCs were transfected with adenovirus carrying the human Cu, Zn-SOD gene and/or the human catalase gene. This resulted in a high level of Cu, Zn-SOD and/or catalase overexpression and decreased oxLDL-induced proliferation. Cu, Zn-SOD and/or catalase also arrested cell cycle progression, which was associated with decreased expression of cyclin D1, cyclin E, CDK2, and CDK4 and upregulation of p21(Cip1) and p27(Kip1). Phosphorylation studies on ERK1/2, JNK, and p38, three major subgroups of mitogen activator protein kinases, demonstrated that Cu, Zn-SOD and/or catalase overexpression suppressed ERK1/2 and JNK phosphorylation. Gel-mobility shift analysis showed that oxLDL caused an increase in the DNA binding activity of activator protein-1 (AP-1) and nuclear factor kappaB (NF-kappaB), which was inhibited by Cu, Zn-SOD and/or catalase overexpression. These results provide the first evidence that overexpression of Cu, Zn-SOD and/or catalase in HASMCs attenuates the cell proliferation caused by oxLDL stimulation and that this inhibitory effect is mediated via downregulation of ERK1/2 and JNK phosphorylation and AP-1 and NF-kappaB inactivation. These observations support the feasibility of the increase of Cu, Zn-SOD and/or catalase expression in human smooth muscle cells as a means of protection against oxidant injury.

Aorta↗
PubMed2006

Downregulation of the constitutively expressed Hsc70 in diabetic myocardium is mediated by insulin deficiency.

The 70 kDa heat shock protein family plays important cardiac protective roles against myocardial injuries. Reduced myocardial protection is a common feature of diabetic myocardium. This study was carried out to define the changes in the 70 kDa heat shock protein family in the myocardium in the of streptozotocin-diabetes rats, and to explore the mechanisms through which diabetes alters the abundance of Hsp70/Hsc70 in cardiac muscle. In the diabetic myocardium, the abundance of Hsc70 was significantly reduced. The abundance of Hsp70 was low in cardiac muscle and was not induced in the diabetic myocardium. Unlike Hsp60, Hsp70 and Hsc70 did not augment insulin-like growth factor-I receptor signaling in cardiac muscle cells. In cultured cardiomyocytes, insulin directly increased the abundance of Hsc70, whereas insulin could not modulate Hsp70. Treating diabetic rats with insulin restored myocardial Hsc70 level, but phlorizin treatment failed to restore myocardial Hsc70. These in vivo and in vitro studies showed that downregulation of Hsc70 in diabetic myocardium was secondary to insulin deficiency. Thus, insulin played a major role in maintaining adequate expression of Hsc70 in cardiac muscle.

Adenoviridae↗
PubMed2005

Lipoprotein lipase gene is linked and associated with hypertension in Taiwan young-onset hypertension genetic study.

Hypertriglyceridemia has been extensively associated with hypertension. However, the mechanism behind it is poorly understood. A positive linkage signal between Lipoprotein lipase (LPL) and young-onset hypertension has been identified by us as the strongest among 18 candidate genes. Here we report our fine mapping works with seven microsatellite markers flanking LPL, sequencing results for its promoter and exons, and an extended association study with the identified single nucleotide polymorphisms(SNP). First, using data from 213 individuals in 59 nuclear families of young-onset hypertension, multipoint analysis revealed a NPL score of 3.02 for the LPL (GZ-14/GZ-15) marker in intron 6. LPL marker (p < 10(-12)) and the haplotypes containing its allele 1 (p < 0.0001) were also significantly associated with young hypertension by transmission disequilibrium test. In-depth sequencing revealed no mutation in promoter and exon regions, except two cSNP: 7754C--> A (C/A: 0.91/0.09), a silent mutation in exon 8 and S447X (C/G: 0.92/0.08), a stop codon mutation in exon 9. Other 11 cSNPs documented in NCBI GenBank are absent in our sample. Constructed from the above 2 cSNPs, haplotype AC showed a moderate TDT association with elevated triglyceride (p = 0.02) and with hypertension and elevated triglyceride combined (p = 0.06). Again, in an extended case-control study, a significant association was found between S447X and patients with persistent hypertension and elevated triglyceride (p = 0.02). We conclude that LPL variants may play a causal role in the development of hypertension in Taiwan Han Chinese. The moderate association with SNP haplotype suggests that other regulatory LPL variant may exist.

Adult↗
PubMed2005

Circulating mononuclear superoxide production and inflammatory markers for long-term prognosis in patients with cardiac syndrome X.

Increased oxidative stress and vascular inflammation have been shown in patients with cardiac syndrome X (CSX; angina, exercise-induced ischemia, and normal coronary angiogram). This study was conducted to assess the impact of basal superoxide generation by circulating mononuclear cells (MNCs), a contributor to intravascular oxidative stress, and serum inflammatory biomarkers, including high-sensitivity C-reactive protein, homocysteine, soluble intercellular adhesion molecule-1, soluble vascular adhesion molecule-1, and von Willebrand factor, on the long-term prognosis of CSX. During a mean follow-up of 31.5 +/- 14.2 months (maximum 5 years), a total of 12 events were recorded in 92 consecutive CSX patients. There were no deaths or myocardial infarctions, but 8 hospitalizations for acute coronary syndrome, 3 for stroke, and 1 for congestive heart failure due to left ventricular systolic dysfunction. Under univariate analysis, only basal superoxide generation by MNCs was associated with the risk for cardiovascular event. Based on multivariate analysis, basal superoxide generation by MNCs could still independently predict future events (relative risk for the highest compared to the lowest tertile, 3.87; 95% confidence interval, 1.42-10.54, p = 0.008). These findings demonstrate that long-term prognosis is fair in patients with CSX. Basal superoxide production of MNCs independently predicts future cardiovascular events, suggesting its potential role in measuring disease progression and risk stratification in these patients.

Aged↗
PubMed2005

Long-term exposure to oxidized low-density lipoprotein enhances tumor necrosis factor-alpha-stimulated endothelial adhesiveness of monocytes by activating superoxide generation and redox-sensitive pathways.

This study was conducted to investigate the role of oxidized low-density lipoprotein (LDL) in monocyte/mononuclear cell (MNC) activation during atherogenesis. First, the activity of MNCs was studied in patients with coronary artery disease (CAD). Compared to normal subjects, phorbol 12-myristate 13-acetate (PMA)-stimulated reactive oxygen species (ROS) production and the adhesiveness to endothelial cells were increased in MNCs from CAD patients. After 24-h coculture with oxidized LDL, ROS elaboration of MNCs was significantly increased in CAD patients. It was further correlated to the endothelial adhesiveness of MNCs (r = 0.561, P < 0.05). Secondly, in an in vitro model for long-term, direct effects of oxidized LDL on murine monocytoid cells (MMCs), oxidized LDL, but not native LDL, induced ROS production of MMCs in a time-dependent manner up to a 4-day coincubation (261% elevation, P < 0.05). Four-day coincubation with ox-LDL enhanced cytoplasmic IkappaB phosphorylation and nuclear factor kappa B (NF-kappaB) translocation and increased endothelial adhesiveness of MMCs. The long-term exposure to oxidized LDL also significantly enhanced tumor necrosis factor-alpha (TNF-alpha)-stimulated ROS production and endothelial adhesiveness of MMCs, which could be completely abolished by the short-term existence of pyrrolidine dithiocarbamate (PDTC), an antioxidant and NF-kappaB blocker and by long-term coincubation with N-acetylcysteine, a nonspecific antioxidant. Accordingly, circulating MNCs were activated with increased endothelial adhesiveness in CAD patients. Long-term exposure to oxidized LDL could directly activate MNCs ex vivo and MMCs in vitro and enhance TNF-alpha-stimulated endothelial adhesiveness through the redox-dependent NF-kappaB transcriptional pathway. The findings suggest the pivotal role of oxidized LDL-induced oxidative stress in monocyte activation during atherogenesis.

Acetylcysteine↗
PubMed2005

L-arginine improves endothelial function and reduces LDL oxidation in patients with stable coronary artery disease.

BACKGROUND: We investigated the effects of oral L-arginine on endothelial function, intravascular oxidative stress, and circulating inflammatory markers in patients with stable coronary artery disease (CAD). METHODS: Thirty-one stable CAD patients were randomly assigned to oral L-arginine (10 g) or vitamin C (500 mg, an antioxidant, as active control) daily for 4 weeks, with crossover to the alternate therapy after 2 weeks off therapy, in this study. Brachial artery endothelial function studies were performed and serum concentrations of lipids and inflammatory markers were measured at baseline, at the end of each 4-week treatment period and at the 2-week wash-out period. Susceptibility of low-density lipoprotein (LDL) particles to oxidation, a marker of oxidative stress, was determined in 11 patients at random before and after 4-week treatment of oral L-arginine. RESULTS: We demonstrates that consumption of either L-arginine or vitamin C significantly increased brachial artery flow-mediated dilatation (mean diameter change from baseline of 4.87%, P<0.0001 and of 3.17%, P=0.0003, respectively). Neither oral L-arginine nor vitamin C affected lipid profiles and circulating levels of inflammatory markers. However, in the 11 patients whose LDL susceptibility to oxidation was determined, lag time significantly increased by 27.1% (P=0.045) after consumption of L-arginine for 4 weeks. CONCLUSIONS: Oral L-arginine supplement improved endothelial function and reduced LDL oxidation in stable CAD patients.

Administration, Oral↗
PubMed2005

Effects of fluvastatin, an HMG-CoA reductase inhibitor, on serum levels of interleukin-18 and matrix metalloproteinase-9 in patients with hypercholesterolemia.

BACKGROUND: Interleukin-18 (IL-18), a novel proinflammatory marker, and matrix metalloproteinase-9 (MMP-9) represent the indices of plaque stability. It is unknown whether hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins), which provide anti-inflammatory and endothelium protection effects, have the property of stabilizing plaque in patients with hypercholesterolemia. HYPOTHESIS: The study was designed to investigate the influence of statin therapy in circulating IL-18, MMP-9, and endothelial function. METHODS: We investigated the effects of a 12-week therapy with fluvastatin on IL-18, MMP-9, and endothelial function in patients with hypercholesterolemia. RESULTS: Compared with placebo, fluvastatin significantly improved flow-mediated vasodilatation to hyperemia, a hallmark of endothelial function [from 3.8% (-3.9 approximately 15.2) to 5.9% (-0.3 approximately 13.2), p = 0.001], and attenuated plasma levels of high sensitivity C-reactive protein (hsCRP) [from 1.3 (0.3 approximately 7.7) to 1.1 mg/l (0.2 approximately 3.5), p = 0.018], IL-18 [from 247.6 (145.4 approximately 378.4) to 196.4 pg/dl (90.7 approximately 380.2), p <0.001], total MMP-9 (from 58 +/- 46.3 to 39.4 +/- 22.4 ng/dl, p = 0.023), and MMP-9 activity [from 6.4 (3.6 approximately 27) to 5.6 ng/dl (3.1 approximately 13.7)]. However, no significant correlation was found between the degree of changes in lipid profile and flow-mediated dilatation (FMD) and plasma concentration of IL-18 and MMP-9. CONCLUSIONS: Fluvastatin reduced plasma concentrations of IL-18 and MMP-9, and improved endothelial function in patients with hypercholesterolemia independent of its lipid-lowering effect.

Aged↗
PubMed2005

Heart rate recovery after exercise and endothelial function--two important factors to predict cardiovascular events.

An attenuated heart rate recovery immediately after exercise, thought to be a marker of reduced parasympathetic activity, has been demonstrated to be an independent predictor of all-cause mortality in several large-scale studies; however, the mechanisms by which impaired heart rate recovery confers an increased risk of death are not clear. From clinical observation, vagal reactivation was thought to be the major determinant of the decrease in heart rate during the first 30 seconds of recovery, independent of age and the intensity of exercise; however, patients with attenuated heart rate recovery were also shown to have lower exercise workload, shorter exercise duration, lower numbers achieving 90% target heart rate, and even impaired endothelial function. This review focuses on the roles of heart rate recovery and endothelial function in predicting future mortality and their interaction.

Age Factors↗
PubMed2005

Antiphospholipid syndrome presenting as intracardiac thrombus with pulmonary embolism.

The presence of antiphospholipid antibodies is associated with arterial and venous thrombosis. A young female with initial presentation of dyspnea and cough that lasted for days is reported. A computed tomographic scan of her chest and echocardiography showed features of thrombus formation over the right atrium, complicated with pulmonary thromboembolism. Antiphospholipid syndrome was diagnosed according to elevated activated partial thromboplastin time, high serum titers of anticardiolipin antibody, and the presence of intracardiac thrombus with pulmonary embolism. This thrombus was subsequently removed successfully with surgical intervention, and the patient's recovery was uneventful.

Adult↗
PubMed2005

Enhanced coronary calcification determined by electron beam CT is strongly related to endothelial dysfunction in patients with suspected coronary artery disease.

BACKGROUND: Coronary artery calcification determined by electron beam CT (EBCT) is strongly associated with total plaque burden but is not related to systemic vascular inflammation. AIMS: We sought to test the hypothesis that enhanced coronary artery calcification, a marker of atherosclerosis and plaque burden, was related to endothelial dysfunction in patients with suspected coronary artery disease (CAD). METHODS AND RESULTS: One hundred twenty-four subjects with suspected CAD were enrolled. Coronary artery calcification was detected by EBCT. A noninvasive method of brachial ultrasound was used to measure endothelium-dependent flow-mediated vasodilation (FMD) and endothelium-independent nitroglycerin-mediated vasodilation (NMD). Serum high-sensitivity C-reactive protein (hsCRP) and monocyte chemoattractant protein-1 (MCP-1) levels were also determined. Of the 124 patients, the calcium scores ranged from 0 to 4,394. All subjects were classified into three groups according to coronary calcium scores: group 1, score 0 (n = 26); group 2, scores 1 to 199 (n = 50); group 3, scores > or = 200 (n = 48). There was an inverse association between the degree of coronary artery calcification and the endothelium-dependent FMD in the three groups (6.9 +/- 0.6% vs 5.3 +/- 0.3% vs 3.7 +/- 0.3%, respectively; p < 0.001) but not the endothelium-independent NMD. Besides, no significant difference in serum levels of hsCRP and MCP-1 were found among the three groups. However, both the serum levels of hsCRP and MCP-1 were correlated significantly with endothelium-dependent FMD (r = - 0.211, p = 0.019; and r = - 0.188, p = 0.037, respectively). By multivariate analysis, enhanced coronary calcification was a strong independent predictor of endothelial dysfunction (p < 0.001). CONCLUSION: Enhanced coronary artery calcification strongly predicted endothelial dysfunction in patients with suspected CAD. Also, serum levels of hsCRP and MCP-1 were significantly correlated with endothelial function. These findings suggested that both calcium deposition and inflammation were involved in endothelial dysfunction.

Aged↗