Abstract:
BACKGROUND:Vascular smooth muscle cell proliferation, migration, and dedifferentiation are critical for vascular diseases. Recently, it was demonstrated that Notch receptors have opposing effects on intima formation after vessel injury. Therefore, it is important to investigate the specific regulatory pathways that activate the different Notch receptors. METHODS AND RESULTS:There was a time- and dose-dependent activation of Notch1 by angiotensin II and platelet-derived growth factor in vascular smooth muscle cells. When phospholipase Cγ1 (PLCγ1) expression was reduced by small interfering RNA, Notch1 activation and Hey2 expression (Notch target gene) induced by angiotensin II or platelet-derived growth factor were remarkably inhibited, while Notch2 degradation was not affected. Mechanistically, we observed an association of PLCγ1 and Akt, which increased after angiotensin II or platelet-derived growth factor stimulation. PLCγ1 knockdown significantly inhibited Akt activation. Importantly, PLCγ1 phospholipase site mutation (no phospholipase activity) did not affect Akt activation. Furthermore, PLCγ1 depletion inhibited platelet-derived growth factor-induced vascular smooth muscle cell proliferation, migration, and dedifferentiation, while it increased apoptosis. In vivo, PLCγ1 and control small interfering RNA were delivered periadventitially in pluronic gel and complete carotid artery ligation was performed. Morphometric analysis 21 days after ligation demonstrated that PLCγ1 small interfering RNA robustly attenuated intima area and intima/media ratio compared with the control group. CONCLUSIONS:PLCγ1-Akt-mediated Notch1 signaling is crucial for intima formation. This effect is attributable to PLCγ1-Akt interaction but not PLCγ1 phospholipase activity. Specific inhibition of the PLCγ1 and Akt interaction will be a promising therapeutic strategy for preventing vascular remodeling.
journal_name
J Am Heart Assocjournal_title
Journal of the American Heart Associationauthors
Jiang D,Zhuang J,Peng W,Lu Y,Liu H,Zhao Q,Chi C,Li X,Zhu G,Xu X,Yan C,Xu Y,Ge J,Pang Jdoi
10.1161/JAHA.117.005537subject
Has Abstractpub_date
2017-07-11 00:00:00issue
7issn
2047-9980pii
JAHA.117.005537journal_volume
6pub_type
杂志文章abstract:BACKGROUND:Obesity is closely associated with various cardiovascular diseases (CVDs). Adipose tissue inflammation and perturbation of adipokine secretion may contribute to the pathogenesis of CVD. This study aimed to evaluate whether the 2 most abundant adipokines, adipocyte-fatty acid binding protein (A-FABP) and adip...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.112.004176
更新日期:2013-01-15 00:00:00
abstract:BACKGROUND:Serum bicarbonate varies over time in chronic kidney disease (CKD) patients, and this variability may portend poor cardiovascular outcomes. The aim of this study was to conduct a time-updated longitudinal analysis to evaluate the association of serum bicarbonate with long-term clinical outcomes: heart failur...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.114.001599
更新日期:2015-04-20 00:00:00
abstract:BACKGROUND:Epinephrine administered during cardiopulmonary resuscitation (CPR) is associated with severe post-resuscitation myocardial dysfunction. We previously demonstrated that therapeutic hypothermia reduced the severity of post-resuscitation myocardial dysfunction caused by epinephrine; however, the relationship b...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.117.006573
更新日期:2018-03-23 00:00:00
abstract::Background Hypodense filling defects within the pulmonary veins on computed tomography described as pulmonary vein sign (PVS) have been noted in acute pulmonary embolism and shown to be associated with poor prognosis. We evaluated venous flow abnormalities in chronic thromboembolic pulmonary hypertension (CTEPH) to de...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.120.018075
更新日期:2020-11-03 00:00:00
abstract::Background Several lipid-lowering therapies reduce CRP (C-reactive protein) independently of LDL-C (low-density lipoprotein cholesterol) reduction, but the association between CRP parameters and benefits from more-intensive LDL-C lowering is inconclusive. We aimed to determine whether the benefits of more- versus less...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章,meta分析
doi:10.1161/JAHA.119.012428
更新日期:2019-08-20 00:00:00
abstract:BACKGROUND:The mechanisms behind the association of atrial fibrillation (AF) and dementia are unknown. We previously found a significantly increased risk of dementia in AF patients taking warfarin with a low percentage of time in therapeutic range. The purpose of this study was to determine the extent to which AF itsel...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.116.003932
更新日期:2016-07-11 00:00:00
abstract:BACKGROUND:Periaortic fat, because of its contiguity with the aorta, may promote vascular remodeling and aortic dilatation. However, the relations between perioartic fat depots and aortic dimensions have not been previously described. METHODS AND RESULTS:A total of 3001 individuals (mean age 50 ± 10 years, 49% women) ...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.112.000885
更新日期:2012-12-01 00:00:00
abstract:BACKGROUND:Sleep disordered breathing in children is associated with increased blood flow velocity and sympathetic overactivity. Sympathetic overactivity results in peripheral vasoconstriction and reduced systemic vascular compliance, which increases blood flow velocity during systole. Augmented blood flow velocity is ...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.117.006137
更新日期:2017-07-17 00:00:00
abstract::Background Data on race- and ethnicity-based disparities in the utilization and outcomes of structural heart disease interventions in the United States are scarce. Methods and Results We used the National Inpatient Sample (2011-2016) to examine racial and ethnic differences in the utilization, in-hospital outcomes, an...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.119.012125
更新日期:2019-08-06 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
abstract:BACKGROUND:Perioperative antiplatelet agents potentially increase bleeding after non-ST-segment elevation (NSTE) acute coronary syndromes (ACS). The protease-activated receptor 1 antagonist vorapaxar reduced cardiovascular events and was associated with increased bleeding versus placebo in NSTE ACS, but its efficacy an...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1161/JAHA.115.002546
更新日期:2015-12-15 00:00:00
abstract::Background Regulator of G protein signaling 6 ( RGS 6) is an important member of the RGS family and produces pleiotropic regulatory effects on cardiac pathophysiology. However, the role of RGS 6 protein in cardiomyocytes during angiotensin II - and pressure overload-induced cardiac hypertrophy remain unknown. Methods ...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.118.009179
更新日期:2018-10-02 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 Whether physical activity is a determinant of peripheral artery disease (PAD) remains unclear. We therefore assessed the association of physical activity (amount and intensity) with subsequent risk of hospitalization with PAD and its severe form, critical limb ischemia, in the ARIC (Atherosclerosis Risk in ...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.119.013534
更新日期:2019-11-05 00:00:00
abstract::Background Little attention has been paid to the importance of sex in the long-term prognosis of patients undergoing cardiac surgery. Methods and Results We conducted a retrospective cohort study of Ontario residents, aged ≥40 years, who underwent coronary artery bypass grafting (CABG) and/or aortic, mitral, or tricus...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.119.013260
更新日期:2019-09-03 00:00:00
abstract:BACKGROUND:Recent studies have shown improving survival after cardiac arrest. However, data regarding sex-based disparities in treatment and outcomes after cardiac arrest are limited. METHODS AND RESULTS:We performed a retrospective analysis of all patients suffering cardiac arrest between 2003 and 2012 using the Nati...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.116.003704
更新日期:2016-06-22 00:00:00
abstract:BACKGROUND:Hospital procedures have been associated with cognitive change in older patients. This study aimed to document the prevalence of mild cognitive impairment in individuals undergoing left heart catheterization (LHC) before the procedure and the incidence of cognitive decline to 3 months afterwards. METHODS AN...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.117.008004
更新日期:2018-03-10 00:00:00
abstract::Background Hyperhomocysteinemia is a risk factor for ischemic stroke; however, a targeted treatment strategy is lacking partly because of limited understanding of the causal role of homocysteine in cerebrovascular pathogenesis. Methods and Results In a genetic model of cystathionine beta synthase (CBS) deficiency, we ...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.119.013368
更新日期:2020-02-18 00:00:00
abstract:BACKGROUND:We aimed to determine how single and combination antihypertensive therapy alters risk for diabetes mellitus (DM).Thiazide diuretics (TD), β blockers (BB), and renin-angiotensin system blockers (RASB) impact DM risk while calcium channel blockers (CCB) are neutral. DM risk associated with combinations is uncl...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.113.000125
更新日期:2013-06-10 00:00:00
abstract::Background The "no-reflow phenomenon" compromises percutaneous coronary intervention outcomes. There is an unmet need for a device that prevents no-reflow phenomenon. Our goal was to develop a guidewire platform comprising a nondisruptive hydrophilic coating that allows continuous delivery of adenosine throughout a pe...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.120.019275
更新日期:2021-01-26 00:00:00
abstract::Background There are spatial disparities in cardiovascular disease (CVD) mortality related to area-level socioeconomic status (SES) disadvantage, but little is known about the spatial distribution of CVD mortality according to built environment factors. We examined joint associations of neighborhood walkability attrib...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.119.016152
更新日期:2020-06-16 00:00:00
abstract:BACKGROUND:Although choline metabolism has been associated with atherosclerotic heart disease, less research attention has been paid to the associations of choline and its oxidative metabolite betaine with cardiac arrhythmias. METHODS AND RESULTS:We evaluated associations of plasma concentrations and dietary intakes o...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章,多中心研究
doi:10.1161/JAHA.117.008190
更新日期:2018-04-12 00:00:00
abstract:BACKGROUND:Inappropriate sinus tachycardia (IST) and postural tachycardia syndrome (POTS) are 2 disorders characterized by sinus tachycardia. It is debated whether the pathophysiology of IST and POTS results from abnormal autonomic regulation or abnormal sinus node function. We hypothesized that intrinsic heart rate (I...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.113.000700
更新日期:2014-04-10 00:00:00
abstract:BACKGROUND:Lower levels of circulating progenitor cells (PCs) reflect impaired endogenous regenerative capacity and are associated with aging, vascular disease, and poor outcomes. Whether biologic sex and sex hormones influence PC numbers remains a subject of controversy. We sought to determine sex differences in circu...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.117.006245
更新日期:2017-10-03 00:00:00
abstract::Background Atrial fibrillation (AF) is associated with cognitive decline. Whether left atrial enlargement (LAE), a critical substrate for AF, is also associated is less well established. Therefore, we assessed the association of LAE and AF with cognitive decline in the ARIC-NCS (Atherosclerosis Risk in Communities Neu...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.119.013197
更新日期:2019-12-03 00:00:00
abstract:BACKGROUND:Among the growing numbers of patients with heart failure, up to one half have heart failure with preserved ejection fraction (HFpEF). The lack of effective treatments for HFpEF is a substantial and escalating unmet clinical need-and the lack of HFpEF-specific animal models represents a major preclinical barr...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.117.007451
更新日期:2018-06-01 00:00:00
abstract::Background The ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial failed to show a reduction in hard clinical end points with an early invasive strategy in stable ischemic heart disease (SIHD). However, the influence of left main disease and high-risk coronary...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.120.018104
更新日期:2021-01-05 00:00:00
abstract:BACKGROUND:Many patients requiring a pacemaker have persistent hypertension with systolic blood pressures above recommended levels. We evaluated a pacemaker-based Programmable Hypertension Control (PHC) therapy that uses a sequence of variably timed shorter and longer atrioventricular intervals. METHODS AND RESULTS:Pa...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1161/JAHA.117.006974
更新日期:2017-12-23 00:00:00
abstract::Background We systematically reviewed trials comparing different reperfusion strategies for ST-segment-elevation myocardial infarction and used multivariate network meta-analysis to compare outcomes across these strategies. Methods and Results We identified 31 contemporary trials in which patients with ST-segment-elev...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.119.015186
更新日期:2020-06-16 00:00:00
abstract:BACKGROUND:Although a stroke event often leads to work disability, diagnoses behind work disability before and after stroke are largely unknown. We examined the pre-event and postevent trends in diagnosis-specific work disability among patients of working age. METHODS AND RESULTS:We included all new nonfatal stroke ev...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.117.006991
更新日期:2018-01-04 00:00:00