Abstract:
BACKGROUND:The liver X receptors (LXRs; α/β) are nuclear receptors known to regulate cholesterol homeostasis and the production of select hematopoietic populations. The objective of this study was to determine the importance of LXRs and a high-fat high-cholesterol diet on global hematopoiesis, with special emphasis on endothelial progenitor cells (EPCs), a vasoreparative cell type that is derived from bone marrow hematopoietic stem cells. METHODS AND RESULTS:Wild-type and LXR double-knockout (Lxrαβ -/- ) mice were fed a Western diet (WD) to increase plasma cholesterol levels. In WD-fed Lxrαβ -/- mice, flow cytometry and complete blood cell counts revealed that hematopoietic stem cells, a myeloid progenitor, and mature circulating myeloid cells were increased; EPC numbers were significantly decreased. Hematopoietic stem cells from WD-fed Lxrαβ -/- mice showed increased cholesterol content, along with increased myeloid colony formation compared with chow-fed mice. In contrast, EPCs from WD-fed Lxrαβ -/- mice also demonstrated increased cellular cholesterol content that was associated with greater expression of the endothelial lineage markers Cd144 and Vegfr2, suggesting accelerated differentiation of the EPCs. Treatment of human umbilical vein endothelial cells with conditioned medium collected from these EPCs increased THP-1 monocyte adhesion. Increased monocyte adhesion to conditioned medium-treated endothelial cells was recapitulated with conditioned medium from Lxrαβ -/- EPCs treated with cholesterol ex vivo, suggesting cholesterol is the main component of the WD inducing EPC dysfunction. CONCLUSIONS:LXRs are crucial for maintaining the balance of hematopoietic cells in a hypercholesterolemic environment and for mitigating the negative effects of cholesterol on EPC differentiation/secretome changes that promote monocyte-endothelial adhesion.
journal_name
J Am Heart Assocjournal_title
Journal of the American Heart Associationauthors
Rasheed A,Tsai R,Cummins CLdoi
10.1161/JAHA.117.007787subject
Has Abstractpub_date
2018-05-08 00:00:00issue
10issn
2047-9980pii
JAHA.117.007787journal_volume
7pub_type
杂志文章abstract::Background Short-term variability of the QT interval (STVQT) has been proposed as a novel electrophysiological marker for the prediction of imminent ventricular arrhythmias in animal models. Our aim is to study whether STVQT can predict imminent ventricular arrhythmias in patients. Methods and Results In 2331 patients...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.120.018133
更新日期:2020-12-01 00:00:00
abstract::Background Programs targeting the standard modifiable cardiovascular risk factors (SMuRFs: hypertension, diabetes mellitus, hypercholesterolemia, smoking) are critical to tackling coronary heart disease at a community level. However, myocardial infarction in SMuRF-less individuals is not uncommon. This study uses 2 se...
journal_title:Journal of the American Heart Association
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doi:10.1161/JAHA.119.013296
更新日期:2019-11-05 00:00:00
abstract::Background The overall goal of this longitudinal study was to determine if the Black population has decreased myocardial function, which has the potential to lead to the early development of congestive heart failure, compared with the White population. Methods and Results A total of 673 subjects were evaluated over a ...
journal_title:Journal of the American Heart Association
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doi:10.1161/JAHA.119.015612
更新日期:2021-01-18 00:00:00
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journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.116.005434
更新日期:2017-09-22 00:00:00
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journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.116.004014
更新日期:2016-11-23 00:00:00
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journal_title:Journal of the American Heart Association
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doi:10.1161/JAHA.119.015379
更新日期:2020-10-20 00:00:00
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journal_title:Journal of the American Heart Association
pub_type: 杂志文章,随机对照试验
doi:10.1161/JAHA.116.004811
更新日期:2017-02-07 00:00:00
abstract::Background Sex differences in outcome have been reported in patients with congenital long QT syndrome. We aimed to report on the incidence of time-dependent life-threatening events in male and female patients with long QT syndrome with an implantable cardioverter defibrillator (ICD). Methods and Results A total of 60 ...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.120.016398
更新日期:2020-10-20 00:00:00
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journal_title:Journal of the American Heart Association
pub_type: 杂志文章,多中心研究
doi:10.1161/JAHA.117.005967
更新日期:2017-09-18 00:00:00
abstract::Background Aerobic exercise capacity is inversely associated with cardiovascular and all-cause mortality in men and women without coronary artery disease (CAD); however, a higher amount of vigorous exercise is associated with a J-shaped relationship in CAD patients. Therefore, the optimal type and amount of exercise f...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.119.014919
更新日期:2020-04-07 00:00:00
abstract::Background There are limited data about cardiac resynchronization therapy (CRT) in adult congenital heart disease. We aimed to assess early and late outcomes of CRT among patients with adult congenital heart disease. Methods and Results We retrospectively studied 54 patients with adult congenital heart disease (median...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.119.012744
更新日期:2019-11-05 00:00:00
abstract:BACKGROUND:Hypertension is a frequent risk factor for the development of heart failure with preserved ejection fraction (HFPEF). Progressive extracellular matrix accumulation has been presumed to be the fundamental pathophysiologic mechanism that leads to the transition to impaired diastolic reserve. However, the contr...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.114.001293
更新日期:2014-12-02 00:00:00
abstract::Background It is uncertain whether there is an association between left ventricular (LV) ejection fraction ( LVEF ) or LV wall motion abnormality and embolic stroke of undetermined source ( ESUS ). Methods and Results We performed a retrospective, cross-sectional study of patients with acute ischemic stroke enrolled i...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.118.011593
更新日期:2019-05-07 00:00:00
abstract:BACKGROUND:Patients receiving oral anticoagulation in addition to dual-antiplatelet therapy are known to be at high risk for bleeding events; thus, the selection of a drug-eluting stent (DES) versus a bare metal stent (BMS) can have important implications for patients with atrial fibrillation (AF) presenting with acute...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.116.005280
更新日期:2017-08-21 00:00:00
abstract:BACKGROUND:Vascular calcification is a common feature in patients with chronic kidney disease (CKD). CKD increases serum levels of tumor necrosis factor-α (TNFα), a critical mediator of vascular calcification. However, the molecular mechanism by which TNFα promotes CKD-dependent vascular calcification remains obscure. ...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.113.000238
更新日期:2013-09-05 00:00:00
abstract::Background The incidence of conduction abnormalities requiring permanent pacemaker implantation (PPI) after transcatheter aortic valve replacement (TAVR) with early and later generation prostheses remains debated. Methods and Results Based on the administrative hospital-discharge database, we collected information for...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.120.015896
更新日期:2020-05-05 00:00:00
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journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.117.005897
更新日期:2017-07-19 00:00:00
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journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.117.005632
更新日期:2017-08-16 00:00:00
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journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.119.015629
更新日期:2020-04-07 00:00:00
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journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.117.006183
更新日期:2017-07-05 00:00:00
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journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.118.010653
更新日期:2018-11-20 00:00:00
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journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.116.003601
更新日期:2017-02-10 00:00:00
abstract:BACKGROUND:The time-sensitive hazard of perioperative cardiac troponin T (cTnT) elevation and whether long-term mortality differs by mechanism of myocardial injury are poorly understood. METHODS AND RESULTS:In this observational study of 12 882 patients who underwent noncardiac vascular surgery, patients were assessed...
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pub_type: 杂志文章
doi:10.1161/JAHA.117.005672
更新日期:2017-06-06 00:00:00
abstract:BACKGROUND:Roux-en-Y gastric bypass (RYGB) reduces obesity-associated comorbidities and cardiovascular mortality. RYGB improves endothelial dysfunction, reducing c-Jun N-terminal kinase (JNK) vascular phosphorylation. JNK activation links obesity with insulin resistance and endothelial dysfunction. Herein, we examined ...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.117.006441
更新日期:2017-11-14 00:00:00
abstract::Background Active commuting is related to a higher level of physical activity but more exposure to ambient air pollutants. With the rather serious air pollution in urban China, we aimed to examine the association between active commuting and risk of incident cardiovascular disease in the Chinese population. Methods an...
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pub_type: 杂志文章,多中心研究
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更新日期:2019-10-15 00:00:00
abstract:BACKGROUND:Participation in cardiac rehabilitation (CR) is an essential component of care for patients with coronary artery disease. However, little is known about its benefit on cardiovascular outcomes in patients with diabetes mellitus (DM) who have undergone percutaneous coronary intervention. The aim of our study w...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.117.006404
更新日期:2017-10-11 00:00:00
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pub_type: 杂志文章
doi:10.1161/JAHA.112.002733
更新日期:2012-08-29 00:00:00
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journal_title:Journal of the American Heart Association
pub_type: 杂志文章
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更新日期:2015-12-16 00:00:00
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更新日期:2018-04-01 00:00:00
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pub_type: 杂志文章,多中心研究
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更新日期:2014-02-28 00:00:00