[有奖活动]circulation Volume 117, Issue 13; April 1, 2008
[b][size=4][color=Blue]circulation Volume 117, Issue 13; April 1, 2008[/color][/size][/b][img]http://circ.ahajournals.org/content/vol117/issue13/cover.gif[/img]
[摘要1]
Differential Behaviors of Atrial Versus Ventricular Fibroblasts: A Potential Role for Platelet-Derived Growth Factor in Atrial-Ventricular Remodeling Differences
Brett Burstein, Eric Libby, Angelino Calderone, and Stanley Nattel
Circulation. 2008;117:1630-1641; published online before print March 17 2008, doi:10.1161/CIRCULATIONAHA.107.748053
Background— In various heart disease paradigms, atria show stronger fibrotic responses than ventricles. The possibility that atrial and ventricular fibroblasts respond differentially to pathological stimuli has not been examined.
Methods and Results— We compared various morphological, secretory, and proliferative response indexes of canine atrial versus ventricular fibroblasts. Cultured atrial fibroblasts showed faster cell surface area increases, distinct morphology at confluence, and greater -smooth muscle actin expression than ventricular fibroblasts. Atrial fibroblast proliferation ([3H]thymidine incorporation) responses were consistently greater for a range of growth factors, including fetal bovine serum, platelet-derived growth factor (PDGF), basic fibroblast growth factor, angiotensin II, endothelin-1, and transforming growth factor-β1. Normal atrial tissue showed larger myofibroblast density compared with ventricular tissue, and the difference was exaggerated by congestive heart failure. Congestive heart failure atria showed larger fractions of fibroblasts in mitotic phases compared with ventricles and displayed enhanced gene expression of fibroblast-selective markers (collagen-1, collagen-3, fibronectin-1). Gene microarrays revealed 225 differentially expressed transcript probe sets between paired atrial and ventricular fibroblast samples, including extracellular matrix (eg, fibronectin, laminin, fibulin), cell signaling (PDGF, PDGF receptor, angiopoietin, vascular endothelial growth factor), structure (keratin), and metabolism (xanthine dehydrogenase) genes, identifying PDGF as a candidate contributor to atrial-ventricular fibroblast differences. PDGF receptor gene expression was greater in normal atrium compared with ventricle, and congestive heart failure differentially enhanced atrial versus ventricular PDGF and PDGF receptor gene expression. PDGF receptor protein expression and -smooth muscle actin protein expression were enhanced in isolated congestive heart failure fibroblasts. The PDGF receptor tyrosine kinase inhibitor AG1295 eliminated fetal bovine serum– and transforming growth factor-β1–stimulated atrial-ventricular fibroblast proliferative response differences.
Conclusions— Atrial fibroblasts behave differently than ventricular fibroblasts over a range of in vitro and in vivo paradigms, with atrial fibroblasts showing enhanced reactivity that may explain greater atrial fibrotic responses. PDGF signaling is particularly important for atrium-selective fibroblast responses and may represent a novel target for arrhythmogenic atrial structural remodeling prevention.
[摘要2]
Fractalkine Deficiency Markedly Reduces Macrophage Accumulation and Atherosclerotic Lesion Formation in CCR2–/– Mice: Evidence for Independent Chemokine Functions in Atherogenesis
Noah Saederup, Liana Chan, Sergio A. Lira, and Israel F. Charo
Circulation. 2008;117:1642-1648; published online before print December 28 2007, doi:10.1161/CIRCULATIONAHA.107.743872
Background— Monocyte-derived foam cells are the hallmark of early atherosclerosis, and recent evidence indicates that chemokines play important roles in directing monocyte migration from the blood to the vessel wall. Genetic deletions of monocyte chemoattractant protein-1 (MCP-1, CCL2), fractalkine (CX3CL1), or their cognate receptors, CCR2 and CX3CR1, markedly reduce atherosclerotic lesion size in murine models of atherosclerosis. The aim of this study was to determine whether these 2 chemokines act independently or redundantly in promoting atherogenesis.
Methods and Results— We crossed CX3CL1–/–ApoE–/– and CCR2–/–ApoE–/– mice to create CX3CL1–/–CCR2–/–ApoE–/– triple knockouts and performed a 4-arm atherosclerosis study. Here, we report that deletion of CX3CL1 in CCR2–/– mice dramatically reduced macrophage accumulation in the artery wall and the subsequent development of atherosclerosis. Deletion of CX3CL1 did not reduce the number of circulating monocytes in either "wild-type" ApoE–/– mice or CCR2–/–ApoE–/– mice, which suggests a role for CX3CL1 in the direct recruitment and/or capture of CCR2-deficient monocytes.
Conclusions— These data provide the first in vivo evidence for independent roles for CCR2 and CX3CL1 in macrophage accumulation and atherosclerotic lesion formation and suggest that successful therapeutic strategies may need to target multiple chemokines or chemokine receptors.
[摘要3]
Combined Inhibition of CCL2, CX3CR1, and CCR5 Abrogates Ly6Chi and Ly6Clo Monocytosis and Almost Abolishes Atherosclerosis in Hypercholesterolemic Mice
Christophe Combadière, Stéphane Potteaux, Mathieu Rodero, Tabassome Simon, Adeline Pezard, Bruno Esposito, Régine Merval, Amanda Proudfoot, Alain Tedgui, and Ziad Mallat
Circulation. 2008;117:1649-1657; published online before print March 17 2008, doi:10.1161/CIRCULATIONAHA.107.745091
Background— Monocytes are critical mediators of atherogenesis. Deletion of individual chemokines or chemokine receptors leads to significant but only partial inhibition of lesion development, whereas deficiency in other signals such as CXCL16 or CCR1 accelerates atherosclerosis. Evidence that particular chemokine pathways may cooperate to promote monocyte accumulation into inflamed tissues, particularly atherosclerotic arteries, is still lacking.
Methods and Results— Here, we show that chemokine-mediated signals critically determine the frequency of monocytes in the blood and bone marrow under both noninflammatory and atherosclerotic conditions. Particularly, CCL2-, CX3CR1-, and CCR5-dependent signals differentially alter CD11b+ Ly6G– 7/4hi (also known as Ly6Chi) and CD11b+ Ly6G– 7/4lo (Ly6Clo) monocytosis. Combined inhibition of CCL2, CX3CR1, and CCR5 in hypercholesterolemic, atherosclerosis-susceptible apolipoprotein E–deficient mice leads to abrogation of bone marrow monocytosis and to additive reduction in circulating monocytes despite persistent hypercholesterolemia. These effects are associated with a marked and additive 90% reduction in atherosclerosis. Interestingly, lesion size highly correlates with the number of circulating monocytes, particularly the CD11b+ Ly6G– 7/4lo subset.
Conclusions— CCL2, CX3CR1, and CCR5 play independent and additive roles in atherogenesis. Signals mediated through these pathways critically determine the frequency of circulating monocyte subsets and thereby account for almost all macrophage accumulation into atherosclerotic arteries.
[摘要4]
Abdominal Obesity and the Risk of All-Cause, Cardiovascular, and Cancer Mortality: Sixteen Years of Follow-Up in US Women
Cuilin Zhang, Kathryn M. Rexrode, Rob M. van Dam, Tricia Y. Li, and Frank B. Hu
Circulation. 2008;117:1658-1667; published online before print March 24 2008, doi:10.1161/CIRCULATIONAHA.107.739714
Background— Accumulating evidence indicates that abdominal adiposity is positively related to cardiovascular disease (CVD) risk and some other diseases independently of overall adiposity. However, the association of premature death resulting from these diseases with abdominal adiposity has not been widely studied, and findings are inconsistent.
Methods and Results— In a prospective cohort study of 44 636 women in the Nurses’ Health Study, associations of abdominal adiposity with all-cause and cause-specific mortality were examined. During 16 years of follow-up, 3507 deaths were identified, including 751 cardiovascular deaths and 1748 cancer deaths. After adjustment for body mass index and potential confounders, the relative risks across the lowest to the highest waist circumference quintiles were 1.00, 1.11, 1.17, 1.31, and 1.79 (95% confidence interval [CI], 1.47 to 1.98) for all-cause mortality; 1.00, 1.04, 1.04, 1.28, and 1.99 (95% CI, 1.44 to 2.73) for CVD mortality; and 1.00, 1.18, 1.20, 1.34, and 1.63 (95% CI, 1.32 to 2.01) for cancer mortality (all P<0.001 for trend). Among normal-weight women (body mass index, 18.5 to <25 kg/m2), abdominal obesity was significantly associated with elevated CVD mortality: Relative risk associated with waist circumference 88 cm was 3.02 (95% CI, 1.31 to 6.99) and for waist-to-hip ratio >0.88 was 3.45 (95% CI, 2.02 to 6.92). After adjustment for waist circumference, hip circumference was significantly and inversely associated with CVD mortality.
Conclusions— Anthropometric measures of abdominal adiposity were strongly and positively associated with all-cause, CVD, and cancer mortality independently of body mass index. Elevated waist circumference was associated with significantly increased CVD mortality even among normal-weight women.
[摘要5]
Age-Dependent Associations Between Chronic Periodontitis/Edentulism and Risk of Coronary Heart Disease
Thomas Dietrich, Monik Jimenez, Elizabeth A. Krall Kaye, Pantel S. Vokonas, and Raul I. Garcia
Circulation. 2008;117:1668-1674; published online before print March 24 2008, doi:10.1161/CIRCULATIONAHA.107.711507
Background— Several epidemiological studies have suggested periodontitis as a risk factor for coronary heart disease (CHD), but results have been inconsistent.
Methods and Results— We evaluated the association between clinical and radiographic measures of periodontitis, edentulism, and incident CHD (angina, myocardial infarction, or fatal CHD) among 1203 men in the VA Normative Aging and Dental Longitudinal Studies who were followed up with triennial comprehensive medical and dental examinations up to 35 years (median 24 years). Cox proportional hazards models with time-varying effects of exposure and potential confounders were fit. We found a significant dose-dependent association between periodontitis and CHD incidence among men <60 years of age (hazard ratio 2.12, 95% confidence interval 1.26 to 3.60 comparing highest versus lowest category of radiographic bone loss, P for trend=0.02), independent of age, body mass index, smoking, alcohol intake, diabetes mellitus, fasting glucose, total cholesterol, high-density lipoprotein cholesterol, triglycerides, hypertension, systolic and diastolic blood pressure, education, marital status, income, and occupation. No association was found among men >60 years of age. Similar results were found when the sum of probing pocket depths was used as a measure of periodontitis. Among men 60 years of age, edentulous men tended to have a higher risk of CHD than dentate men in the lowest bone loss (hazard ratio 1.61, 95% confidence interval 0.95 to 2.73) and lowest pocket depth (hazard ratio 1.72, 95% confidence interval 1.03 to 2.85) categories, independent of confounders.
Conclusions— Chronic periodontitis is associated with incidence of CHD among younger men, independent of established cardiovascular risk factors.
[摘要6]
Repeated Replication and a Prospective Meta-Analysis of the Association Between Chromosome 9p21.3 and Coronary Artery Disease
Heribert Schunkert, Anika Götz, Peter Braund, Ralph McGinnis, David-Alexandre Tregouet, Massimo Mangino, Patrick Linsel-Nitschke, Francois Cambien, Christian Hengstenberg, Klaus Stark, Stefan Blankenberg, Laurence Tiret, Pierre Ducimetiere, Andrew Keniry, Mohammed J.R. Ghori, Stefan Schreiber, Nour Eddine El Mokhtari, Alistair S. Hall, Richard J. Dixon, Alison H. Goodall, Henrike Liptau, Helen Pollard, Daniel F. Schwarz, Ludwig A. Hothorn, H. -Erich Wichmann, Inke R. König, Marcus Fischer, Christa Meisinger, Willem Ouwehand, Panos Deloukas, John R. Thompson, Jeanette Erdmann, Andreas Ziegler, Nilesh J. Samani for the Cardiogenics Consortium
Circulation. 2008;117:1675-1684; published online before print March 24 2008, doi:10.1161/CIRCULATIONAHA.107.730614
Background— Recently, genome-wide association studies identified variants on chromosome 9p21.3 as affecting the risk of coronary artery disease (CAD). We investigated the association of this locus with CAD in 7 case-control studies and undertook a meta-analysis.
Methods and Results— A single-nucleotide polymorphism (SNP), rs1333049, representing the 9p21.3 locus, was genotyped in 7 case-control studies involving a total of 4645 patients with myocardial infarction or CAD and 5177 controls. The mode of inheritance was determined. In addition, in 5 of the 7 studies, we genotyped 3 additional SNPs to assess a risk-associated haplotype (ACAC). Finally, a meta-analysis of the present data and previously published samples was conducted. A limited fine mapping of the locus was performed. The risk allele (C) of the lead SNP, rs1333049, was uniformly associated with CAD in each study (P<0.05). In a pooled analysis, the odds ratio per copy of the risk allele was 1.29 (95% confidence interval, 1.22 to 1.37; P=0.0001). Haplotype analysis further suggested that this effect was not homogeneous across the haplotypic background (test for interaction, P=0.0079). An autosomal-additive mode of inheritance best explained the underlying association. The meta-analysis of the rs1333049 SNP in 12 004 cases and 28 949 controls increased the overall level of evidence for association with CAD to P=6.04x10–10 (odds ratio, 1.24; 95% confidence interval, 1.20 to 1.29). Genotyping of 31 additional SNPs in the region identified several with a highly significant association with CAD, but none had predictive information beyond that of the rs1333049 SNP.
Conclusion— This broad replication provides unprecedented evidence for association between genetic variants at chromosome 9p21.3 and risk of CAD.
[摘要7]
N-Terminal Prohormone Brain Natriuretic Peptide as a Predictor of Cardiovascular Disease and Mortality in Blacks With Hypertensive Kidney Disease: The African American Study of Kidney Disease and Hypertension (AASK)
B.C. Astor, S. Yi, L. Hiremath, T. Corbin, V. Pogue, B. Wilkening, G. Peterson, J. Lewis, J.P. Lash, F. Van Lente, J. Gassman, X. Wang, G. Bakris, L.J. Appel, and G. Contreras
Circulation. 2008;117:1685-1692; published online before print March 24 2008, doi:10.1161/CIRCULATIONAHA.107.724187
Background— Higher levels of N-terminal prohormone brain-type natriuretic peptide (NT-proBNP) predict cardiovascular disease (CVD) in several disease states, but few data are available in patients with chronic kidney disease or in blacks.
Methods and Results— The African American Study of Kidney Disease and Hypertension trial enrolled hypertensive blacks with a glomerular filtration rate of 20 to 65 mL · min–1 · 1.73 m–2 and no other identified cause of kidney disease. NT-proBNP was measured with a sandwich chemiluminescence immunoassay (coefficient of variation 2.9%) in 994 African American Study of Kidney Disease and Hypertension participants. NT-proBNP was categorized as undetectable, low, moderate, or high. Proteinuria was defined as 24-hour urinary protein–creatinine ratio >0.22. A total of 134 first CVD events (CVD death or hospitalization for coronary artery disease, heart failure, or stroke) occurred over a median of 4.3 years. Participants with high NT-proBNP were much more likely to have a CVD event than participants with undetectable NT-proBNP after adjustment (relative hazard 4.0 [95% confidence interval [CI] 2.1 to 7.6]). A doubling of NT-proBNP was associated with a relative hazard of 1.3 (95% CI 1.0 to 1.6) for coronary artery disease, 1.7 (95% CI 1.4 to 2.2) for heart failure, 1.1 (95% CI 0.9 to 1.4) for stroke, and 1.8 (95% CI 1.4 to 2.4) for CVD death. The association of NT-proBNP with CVD events was significantly stronger (Pinteraction=0.05) in participants with than in those without proteinuria. Higher NT-proBNP was not associated with renal disease progression.
Conclusions— These results suggest that elevated NT-proBNP levels are associated with higher CVD risk among blacks with hypertensive kidney disease. This association may be stronger in individuals with significant proteinuria.
[摘要8]
Interrelation of Coronary Calcification, Myocardial Ischemia, and Outcomes in Patients With Intermediate Likelihood of Coronary Artery Disease: A Combined Positron Emission Tomography/Computed Tomography Study
Matthew P. Schenker, Sharmila Dorbala, Eric Cho Tek Hong, Frank J. Rybicki, Rory Hachamovitch, Raymond Y. Kwong, and Marcelo F. Di Carli
Circulation. 2008;117:1693-1700; published online before print March 24 2008, doi:10.1161/CIRCULATIONAHA.107.717512
Background— Although the value of coronary artery calcium (CAC) for atherosclerosis screening is gaining acceptance, its efficacy in predicting flow-limiting coronary artery disease remains controversial, and its incremental prognostic value over myocardial perfusion is not well established.
Methods and Results— We evaluated 695 consecutive intermediate-risk patients undergoing combined rest-stress rubidium 82 positron emission tomography (PET) perfusion imaging and CAC scoring on a hybrid PET-computed tomography (CT) scanner. The frequency of abnormal scans among patients with a CAC score 400 was higher than that in patients with a CAC score of 1 to 399 (48.5% versus 21.7%, P<0.001). Multivariate logistic regression supported the concept of a threshold CAC score 400 governing this relationship (odds ratio 2.91, P<0.001); however, the frequency of ischemia among patients with no CAC was 16.0%, and its absence only afforded a negative predictive value of 84.0%. Risk-adjusted survival analysis demonstrated a stepwise increase in event rates (death and myocardial infarction) with increasing CAC scores in patients with and without ischemia on PET myocardial perfusion imaging. Among patients with normal PET myocardial perfusion imaging, the annualized event rate in patients with no CAC was lower than in those with a CAC score 1000 (2.6% versus 12.3%, respectively). Likewise, in patients with ischemia on PET myocardial perfusion imaging, the annualized event rate in those with no CAC was lower than among patients with a CAC score 1000 (8.2% versus 22.1%).
Conclusions— Although increasing CAC content is generally predictive of a higher likelihood of ischemia, its absence does not completely eliminate the possibility of flow-limiting coronary artery disease. Importantly, a stepwise increase occurs in the risk of adverse events with increasing CAC scores in patients with and without ischemia on PET myocardial perfusion imaging.
[摘要9]
Microsomal Prostaglandin E2 Synthase-1 Deletion Leads to Adverse Left Ventricular Remodeling After Myocardial Infarction
Norbert Degousee, Shafie Fazel, Denis Angoulvant, Eva Stefanski, Sven-Christian Pawelzik, Marina Korotkova, Sara Arab, Peter Liu, Thomas F. Lindsay, Sun Zhuo, Jagdish Butany, Ren-Ke Li, Laurent Audoly, Ronald Schmidt, Carlo Angioni, Gerd Geisslinger, Per-Johan Jakobsson, and Barry B. Rubin
Circulation. 2008;117:1701-1710; published online before print March 17 2008, doi:10.1161/CIRCULATIONAHA.107.749739
Background— Pharmacological inhibition of cyclooxygenase-2 increases the risk of myocardial infarction (MI) and stroke. Microsomal prostaglandin (PG) E2 synthase-1 (mPGES-1), encoded by the Ptges gene, functions downstream from cyclooxygenase-2 in the inducible PGE2 biosynthetic pathway. We caused acute MI in Ptges+/+ and Ptges–/– mice to define the role of mPGES-1 in cardiac ischemic injury.
Methods and Results— Twenty-eight days after MI, Ptges–/– mice develop more left ventricular (LV) dilation, have worse LV systolic and diastolic function, and have higher LV end-diastolic pressure than Ptges+/+ mice but have similar pulmonary wet-to-dry weight ratios, cardiac mass, infarct size, and mortality. The length-to-width ratio of individual cardiomyocytes is significantly greater in Ptges–/– than Ptges+/+ mice after MI, a finding consistent with eccentric cardiomyocyte hypertrophy in Ptges–/– mice. Expression of atrial natriuretic peptide, brain natriuretic peptide, and - and β-myosin heavy chain, markers of ventricular hypertrophy, is higher in the LV of Ptges–/– than Ptges+/+ mice after MI. Ptges+/+ mice express cyclooxygenase-2 and mPGES-1 protein in inflammatory cells adjacent to the infarct after MI but do not express these proteins in cardiomyocytes. Ptges–/– mice express cyclooxygenase-2 in inflammatory cells adjacent to the infarct and do not express mPGES-1 in any cells in the heart. Levels of PGE2 but not PGD2, thromboxane A2, PGI2, or PGF2 are higher in the infarct and LV remote from the infarct after MI in Ptges+/+ than Ptges–/– mice.
Conclusions— In Ptges+/+ mice, mPGES-1 in inflammatory cells catalyzes PGE2 biosynthesis in the LV after MI. Deletion of mPGES-1 leads to eccentric cardiac myocyte hypertrophy, LV dilation, and impaired LV contractile function after acute MI.
[摘要10]
Clinical Predictors for Fatal Pulmonary Embolism in 15 520 Patients With Venous Thromboembolism: Findings From the Registro Informatizado de la Enfermedad TromboEmbolica venosa (RIETE) Registry
Silvy Laporte, Patrick Mismetti, Hervé Décousus, Fernando Uresandi, Remedios Otero, Jose Luis Lobo, Manuel Monreal, and the RIETE Investigators
Circulation. 2008;117:1711-1716; published online before print March 17 2008, doi:10.1161/CIRCULATIONAHA.107.726232
Background— Clinical predictors for fatal pulmonary embolism (PE) in patients with venous thromboembolism have never been studied.
Methods and Results— Using data from the international prospective Registro Informatizado de la Enfermedad TromboEmbolica venosa (RIETE) registry about patients with objectively confirmed symptomatic acute venous thromboembolism, we determined independent predictive factors for fatal PE. Between March 2001 and July 2006, 15 520 consecutive patients (mean age±SD, 66.3±16.9 years; 49.7% men) with acute venous thromboembolism were included. Symptomatic deep-vein thrombosis without symptomatic PE was observed in 58.0% (n=9008) of patients, symptomatic nonmassive PE in 40.4% (n=6264), and symptomatic massive PE in 1.6% (n=248). At 3 months, the cumulative rates of overall mortality and fatal PE were 8.65% and 1.68%, respectively. On multivariable analysis, patients with symptomatic nonmassive PE at presentation exhibited a 5.42-fold higher risk of fatal PE compared with patients with deep-vein thrombosis without symptomatic PE (P<0.001). The risk of fatal PE was multiplied by 17.5 in patients presenting with a symptomatic massive PE. Other clinical factors independently associated with an increased risk of fatal PE were immobilization for neurological disease, age >75 years, and cancer.
Conclusion— PE remains a potentially fatal disease. The clinical predictors identified in the present study should be included in any clinical risk stratification scheme to optimally adapt the treatment of PE to the risk of the fatal outcome.
[摘要11]
Percutaneous and Minimally Invasive Valve Procedures: A Scientific Statement From the American Heart Association Council on Cardiovascular Surgery and Anesthesia, Council on Clinical Cardiology, Functional Genomics and Translational Biology Interdisciplinary Working Group, and Quality of Care and Outcomes Research Interdisciplinary Working Group
Todd K. Rosengart, Ted Feldman, Michael A. Borger, Thomas A. Vassiliades, Jr, A. Marc Gillinov, Katherine J. Hoercher, Alec Vahanian, Robert O. Bonow, and William O’Neill
Circulation. 2008;117:1750-1767; published online before print March 10 2008, doi:10.1161/CIRCULATIONAHA.107.188525
The incidence of valvular heart disease is expected to increase over the next several decades as a large proportion of the US demographic advances into the later decades of life. At the same time, the next several years can be anticipated to bring a broad transition of surgical therapy to minimally invasive (minithoracotomy and small port) access and the more gradual introduction of percutaneous approaches for the correction of valvular heart disease. Broad acceptance of these technologies will require careful and sometimes perplexing comparisons of the outcomes of these new technologies with existing standards of care. The validation of percutaneous techniques, in particular, will require the collaboration of cardiologists and cardiac surgeons in centers with excellent surgical and catheter experience and a commitment to trial participation. For the near term, percutaneous techniques will likely remain investigational and will be limited in use to patients considered to be high risk or to inoperable surgical candidates. Although current-generation devices and techniques require significant modification before widespread clinical use can be adopted, it must be expected that less invasive and even percutaneous valve therapies will likely have a major impact on the management of patients with valvular heart disease over the next several years.
[[i] 本帖最后由 tnp007 于 2008-4-1 22:38 编辑 [/i]] **** Hidden Message *****
[[i] 本帖最后由 tnp007 于 2008-4-1 22:39 编辑 [/i]] [size=4]
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[[i] 本帖最后由 tnp007 于 2008-4-1 22:49 编辑 [/i]] 认领第1篇，支持一下！[biggrin] 终于完成了第1篇啊！
[摘要1]
Differential Behaviors of Atrial Versus Ventricular Fibroblasts: A Potential Role for Platelet-Derived Growth Factor in Atrial-Ventricular Remodeling Differences
Brett Burstein, Eric Libby, Angelino Calderone, and Stanley Nattel
Circulation. 2008;117:1630-1641; published online before print March 17 2008, doi:10.1161/CIRCULATIONAHA.107.748053
Background— In various heart disease paradigms, atria show stronger fibrotic responses than ventricles. The possibility that atrial and ventricular fibroblasts respond differentially to pathological stimuli has not been examined.
Methods and Results— We compared various morphological, secretory, and proliferative response indexes of canine atrial versus ventricular fibroblasts. Cultured atrial fibroblasts showed faster cell surface area increases, distinct morphology at confluence, and greater -smooth muscle actin expression than ventricular fibroblasts. Atrial fibroblast proliferation ([3H]thymidine incorporation) responses were consistently greater for a range of growth factors, including fetal bovine serum, platelet-derived growth factor (PDGF), basic fibroblast growth factor, angiotensin II, endothelin-1, and transforming growth factor-β1. Normal atrial tissue showed larger myofibroblast density compared with ventricular tissue, and the difference was exaggerated by congestive heart failure. Congestive heart failure atria showed larger fractions of fibroblasts in mitotic phases compared with ventricles and displayed enhanced gene expression of fibroblast-selective markers (collagen-1, collagen-3, fibronectin-1). Gene microarrays revealed 225 differentially expressed transcript probe sets between paired atrial and ventricular fibroblast samples, including extracellular matrix (eg, fibronectin, laminin, fibulin), cell signaling (PDGF, PDGF receptor, angiopoietin, vascular endothelial growth factor), structure (keratin), and metabolism (xanthine dehydrogenase) genes, identifying PDGF as a candidate contributor to atrial-ventricular fibroblast differences. PDGF receptor gene expression was greater in normal atrium compared with ventricle, and congestive heart failure differentially enhanced atrial versus ventricular PDGF and PDGF receptor gene expression. PDGF receptor protein expression and -smooth muscle actin protein expression were enhanced in isolated congestive heart failure fibroblasts. The PDGF receptor tyrosine kinase inhibitor AG1295 eliminated fetal bovine serum– and transforming growth factor-β1–stimulated atrial-ventricular fibroblast proliferative response differences.
Conclusions— Atrial fibroblasts behave differently than ventricular fibroblasts over a range of in vitro and in vivo paradigms, with atrial fibroblasts showing enhanced reactivity that may explain greater atrial fibrotic responses. PDGF signaling is particularly important for atrium-selective fibroblast responses and may represent a novel target for arrhythmogenic atrial structural remodeling prevention.
[b]血小板衍生生长因子在房-室重构差异中的潜在作用[/b]
[b]背景-[/b]在各种心血管疾病模型中，心房相对于心室显示出更强的纤维化反应。可能性在于心房和心室对病理刺激所产生的纤维化反应不甚相同，并且这种差异尚未被研究过。
[b]方法与结果-[/b]我们比较了犬类心脏心房与心室成纤维细胞的各项指标，包括形态学的、内分泌学的以及增殖反应指数。与心室成纤维细胞相比，培养中的心房成纤维细胞表面积增加更快，细胞聚集在形态学上更显著，平滑肌肌动蛋白表达更高。心房成纤维细胞增殖反应在一些生长因子作用下持续增强，这些生长因子包括胎牛血清、血小板衍生的生长因子、基本的成纤维细胞生长因子、血管紧张素Ⅱ、内皮素-1及转化生长因子-β1。正常心房组织与心室组织相比，成纤维细胞密度更大，且这种差异在充血性心衰时加剧。充血性心衰时，心房处于M期的成纤维细胞所占比例高于心室，且心房内带有选择性成纤维细胞标志（胶原-1，胶原-3，纤维连接蛋白-1）的基因表达增强。基因芯片研究显示在配对的心房与心室成纤维细胞样本中有225对转录探针为差异性表达，包括细胞外基质 (如纤维连接蛋白，纤维连接蛋白等)、细胞信号 (血小板衍生生长因子，血小板衍生生长因子受体，血管生成素，血管内皮生长因子)、结构 (角蛋白)和新陈代谢 (黄嘌呤脱氢酶)的基因，并确定血小板衍生生长因子作为区分房-室成纤维细胞的候选者。血小板衍生生长因子受体基因表达在心房中要高于心室，并且充血性心衰对增强心房和心室内血小板衍生生长因子与血小板衍生生长因子受体的基因表达有差异。 在离体充血性心衰的心脏内，成纤维细胞血小板衍生生长因子受体蛋白表达与平滑肌蛋白表达增强。血小板衍生生长因子受体酪氨酸激酶抑制剂AG1295能够消除胎牛血清及转化生长因子-β1所诱导的房-室成纤维细胞增殖反应间的差异。
[b]结论-[/b] 在一些体外和体内模型中，心房成纤维细胞在表观上与心室成纤维细胞不同。心房成纤维细胞显示出更强的反应性，这也许是解释心房纤维化反应更强的原因之一。血小板衍生生长因子信号对于选择性心房成纤维细胞反应来说尤其重要，展现出新型的靶向疗法，从而起到预防致心律失常性心房结构重构的作用。
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[[i] 本帖最后由 tnp007 于 2008-4-4 09:03 编辑 [/i]] 希望后来的能对我的翻译提点意见，互相学习，互相进步[biggrin] 2222222222222 [color=Black][font=黑体][size=3]Fractalkine的缺陷由于明显降低巨噬细胞的积累和动脉粥样硬化病变的形成在CCR2转基因老鼠：在动脉粥样硬化中独立的趋化因子的功能证据[/size][/font][/color]
背景资料：单核细胞衍生的泡沫细胞，是标志性的早期动脉粥样硬化，以及最近的证据表明，趋化因子起着重要的作用，在指挥单核细胞迁移，由血液输送到血管壁上。基因缺失的单核细胞趋化蛋白-1 （ MCP-1，ccl2 ） ， fractalkine（ cx3cl1 ） ，或其同源受体， CCR2和CX3CR1 ，显着降低动脉粥样硬化病变的大小，在小鼠模型，动脉粥样硬化。本研究的目的是要确定是否这些二日趋独立行事，或冗余，在促进动脉粥样硬化。
方法和成果：我们跨过cx3cl1-/-apoe-/-和ccr2-/-apoe-/-小鼠cx3cl1-/-ccr2-/-apoe-/-三重打击，并表显出动脉粥样硬化的研究。在这里，我们报告说，cx3cl1在CCR2转基因小鼠显着降低巨噬细胞堆积在血管壁和其后发展的动脉粥样硬化。cx3cl1并未减少多少循环单核无论"野生型" ApoE转基因小鼠或ccr2-/-apoe转基因小鼠，这表明作用cx3cl1在直接招聘和/或捕获的CCR2缺陷单核细胞。
结论：这些数据提供了第一个活体证据的独立角色，为CCR2和cx3cl1在巨噬细胞的积累和动脉粥样硬化病变的形成和提出，成功的治疗策略可能需要针对多种趋化因子或趋化因子受体。
[[i] 本帖最后由 tnp007 于 2008-4-13 17:08 编辑 [/i]] 楼上的兄弟翻译的不是很通顺，好像是用google翻译的吧，希望能好好组织一下！然后给与评分！！ [摘要3]
Combined Inhibition of CCL2, CX3CR1, and CCR5 Abrogates Ly6Chi and Ly6Clo Monocytosis and Almost Abolishes Atherosclerosis in Hypercholesterolemic Mice
Christophe Combadière, Stéphane Potteaux, Mathieu Rodero, Tabassome Simon, Adeline Pezard, Bruno Esposito, Régine Merval, Amanda Proudfoot, Alain Tedgui, and Ziad Mallat
Circulation. 2008;117:1649-1657; published online before print March 17 2008, doi:10.1161/CIRCULATIONAHA.107.745091
Background— Monocytes are critical mediators of atherogenesis. Deletion of individual chemokines or chemokine receptors leads to significant but only partial inhibition of lesion development, whereas deficiency in other signals such as CXCL16 or CCR1 accelerates atherosclerosis. Evidence that particular chemokine pathways may cooperate to promote monocyte accumulation into inflamed tissues, particularly atherosclerotic arteries, is still lacking.
Methods and Results— Here, we show that chemokine-mediated signals critically determine the frequency of monocytes in the blood and bone marrow under both noninflammatory and atherosclerotic conditions. Particularly, CCL2-, CX3CR1-, and CCR5-dependent signals differentially alter CD11b+ Ly6G– 7/4hi (also known as Ly6Chi) and CD11b+ Ly6G– 7/4lo (Ly6Clo) monocytosis. Combined inhibition of CCL2, CX3CR1, and CCR5 in hypercholesterolemic, atherosclerosis-susceptible apolipoprotein E–deficient mice leads to abrogation of bone marrow monocytosis and to additive reduction in circulating monocytes despite persistent hypercholesterolemia. These effects are associated with a marked and additive 90% reduction in atherosclerosis. Interestingly, lesion size highly correlates with the number of circulating monocytes, particularly the CD11b+ Ly6G– 7/4lo subset.
Conclusions— CCL2, CX3CR1, and CCR5 play independent and additive roles in atherogenesis. Signals mediated through these pathways critically determine the frequency of circulating monocyte subsets and thereby account for almost all macrophage accumulation into atherosclerotic arteries.
[b]在高胆固醇血症老鼠模型中，抑制CCL2, CX3CR1与CCR5之间的结合将废除单核白细胞增多中Ly6Chi 和 Ly6Clo的表达，几乎消除动脉粥样硬化。[/b]
[b]背景[/b]-单核细胞是动脉粥样硬化生成的重要介质。个体化学增活素或趋化因子受体缺失虽仅仅是部分抑制动脉粥样硬化损伤进程，但这种缺失是很重要的，然而缺乏CXCL16 或 CCR1等信号将加速动脉粥样硬化的形成。有证据表明特殊趋化因子通路可能促进单核细胞在发炎的组织中聚集，但在动脉粥样硬化的动脉中缺乏显著证据。
[b]方法和结果[/b]-在非炎症性的及动脉粥样硬化的条件下，我们发现趋化因子介导的信号可精密地决定血液和骨髓中单核细胞的表达频率。特别是CCL2-, CX3CR1-和CCR5依赖的信号分别改变了CD11b+ Ly6G–7/4hi 和 CD11b+ Ly6G– 7/4lo (Ly6Clo) 介导的单核白细胞增多。尽管存在持续性的高胆固醇血症，在高胆固醇血症、动脉粥样硬化易感载脂蛋白E缺陷的大鼠中抑制CCL2, CX3CR1和CCR5的结合，会导致骨髓单核白细胞增多的废除和附加的循环单核细胞减少。这些效应与动脉粥样硬化中细胞的·显著且90%额外减少相关。有趣地是，损伤面积与循环中单核细胞特别是CD11b+ Ly6G– 7/4lo亚型数量高度相关。
[b]结论[/b]-在动脉粥样硬化形成中CCL2, CX3CR1和CCR5起独立累加作用。介导的信号通过这些通路精密地决定循环中单核细胞亚型的表达频率，从而解释了几乎所有动脉粥样硬化的动脉中巨噬细胞的聚集现象。
[[i] 本帖最后由 daike_ren 于 2008-4-15 00:18 编辑 [/i]] 好，认领第4篇
[摘要4]
Abdominal Obesity and the Risk of All-Cause, Cardiovascular, and Cancer Mortality: Sixteen Years of Follow-Up in US Women
Cuilin Zhang, Kathryn M. Rexrode, Rob M. van Dam, Tricia Y. Li, and Frank B. Hu
Circulation. 2008;117:1658-1667; published online before print March 24 2008, doi:10.1161/CIRCULATIONAHA.107.739714
腹式肥胖和全因死亡率、心血管死亡率和癌症死亡率：美国妇女十六年的随访分析
背景---越来越多的证据表明腹式肥胖与心血管疾病（CVD）危险因素及其他一些疾病正相关，而与总的脂肪量无关。尽管如此，但这些疾病引起的早期死亡与腹式肥胖的关系还没有进一步的研究，有些研究结果还同时存在争议。
方法和结果——在护士健康研究（NHS）中对44 636名妇女进行了腹式肥胖性相关的全因死亡率和特定死亡率的前瞻性队列研究。经过16年的随访，3507名妇女死亡，包括751名心血管疾病死亡和1748名癌症死亡。在调整了体重指数和潜在混杂因素后，得出最低到最高腰围的相对危险度。全因死亡率的相当危险度五分线分别为1; 1.11; 1.17; 1.31; 1.79（95%可信区间CI为1.47 to 1.98），CVD死亡率五分线为1.00, 1.04, 1.04, 1.28, 和1.99，(95% CI为 1.44 to 2.73)，癌症死亡率五分线为1.00, 1.18, 1.20, 1.34, 和 1.63 (95% CI为 1.32 to 2.01).全部的P<0.001。在正常体重妇女（体重指数18.5 到<25 kg/m2），腹式肥胖度与CVD死亡率的升高明显相关：88cm腰围的相对危险因子为3.02，(95% CI, 1.31 到 6.99)，腰围-臀围比例为0.88的相对危险因子3.45(95% CI, 2.02 到 6.92).对腰围调整后，臀围明显与CVD负相关。
结论——对腹式肥胖测量的结果与全因死亡率、CVD及癌症死亡率明显呈正相关，与个体体重指数无关。甚至在正常体重妇女里，腰围的增加能明显增加CVD死亡率。
[[i] 本帖最后由 hs911 于 2008-4-25 13:59 编辑 [/i]] [摘要6]
Repeated Replication and a Prospective Meta-Analysis of the Association Between Chromosome 9p21.3 and Coronary Artery Disease
Heribert Schunkert, Anika Götz, Peter Braund, Ralph McGinnis, David-Alexandre Tregouet, Massimo Mangino, Patrick Linsel-Nitschke, Francois Cambien, Christian Hengstenberg, Klaus Stark, Stefan Blankenberg, Laurence Tiret, Pierre Ducimetiere, Andrew Keniry, Mohammed J.R. Ghori, Stefan Schreiber, Nour Eddine El Mokhtari, Alistair S. Hall, Richard J. Dixon, Alison H. Goodall, Henrike Liptau, Helen Pollard, Daniel F. Schwarz, Ludwig A. Hothorn, H. -Erich Wichmann, Inke R. König, Marcus Fischer, Christa Meisinger, Willem Ouwehand, Panos Deloukas, John R. Thompson, Jeanette Erdmann, Andreas Ziegler, Nilesh J. Samani for the Cardiogenics Consortium
Circulation. 2008;117:1675-1684; published online before print March 24 2008, doi:10.1161/CIRCULATIONAHA.107.730614
重复复制和前瞻性Meta分析染色体9p21.3区域与冠心病的发病关系
背景 最近，全基因组研究检测表明染色体9p21.3区域变异增加冠心病的风险。我们分析了该区域变异在7个病例对照研究中与冠心病的关系，并进行了Meta分析。
方法和结果 7个病例对照研究（包括4645个心肌梗塞或冠心病病人及5177个健康人）检测9p21.3位点的单核苷酸多态性(SNP), rs1333049，确立了该基因的遗传方式。另外，在其中5项研究中，检测了3个额外的SNP来获得一个危险相关基因型。最后，对目前的数据和之前发布的数据进行meta分析。进行了一个有限的位点指纹分析。rs1333049风险位点（C）在7项研究中都与冠心病相关。在一项混合研究中，风险位点的比值比为1.29(95%置信区间，1.22－1.37；P=0.0001)。基因型分析进一步揭示这种效应的基因型背景不是同质的（相互作用检测，P＝0.0079），通过常染色体遗传比较合理。Meta分析（包含12004病例和28949对照）的结果表明rs1333049与冠心病高度相关， P=6.04x10–10 （比值比，1.24；95％置信区间，1.20－1.29）。9p21.3区域另外31个SNP基因型和冠心病发病相关，但是预测冠心病的发病都未能超过rs1333049。
结论：这项大样本的分析提供充分的证据表明了染色体9p21.3的变异与冠心病高度相关。
[[i] 本帖最后由 sums2001 于 2008-4-27 23:22 编辑 [/i]] 我来领第9篇吧，感觉人气不足阿 第9篇：
前列腺素合成酶E2微粒体敲除可以逆转心梗后的左室重构
背景：在临床药物的应用中发现，抑制环氧化酶2会增加发生心梗和卒中的风险。作为环氧化酶2的下游底物，前列腺素合成酶E2微粒体由ptges基因翻译而来。我们构建了ptges敲除小鼠的心梗模型来观察前列腺素合成酶E2微粒体在心肌缺血损伤中的作用。
方法和结过：在小鼠心梗后28天，ptges敲除的小鼠表现出更为明星的左室扩张，和更差的左室功能。以及更高的左室舒张期末压。但是肺内的干湿比，心容量，梗死面积和死亡率是一致的。在组织学角度，ptges敲除的小鼠在心梗后单个心肌细胞长宽比比野生型大，提示更为明显的离心性心脏肥大。而一些心室重构的蛋白标记，如心房钠尿肽，脑钠尿肽，以及β肌球蛋白重链在ptges敲除的小鼠左室高表达。野生型小鼠在心梗周边由致炎细胞表达的环氧化酶2，前列腺素合成酶E2微粒体，在ptges敲除的小鼠上仅发现有环氧化酶2表达。且各种致炎因子血栓素A2，PGI2, PGF2在野生型小鼠左室局部，心梗后均比ptges敲除小鼠高表达。
结论：在野生型小鼠心梗后，mPGES-1参与了PGE2致炎通路。敲除mPGES-1加重了心梗后小鼠心肌肥大，左室扩张，损害了左心收缩力。
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