Abstract:
BACKGROUND:Cardiac sodium channel (NaV1.5) dysfunction contributes to arrhythmogenesis during pathophysiological conditions. Nav1.5 localizes to distinct subcellular microdomains within the cardiomyocyte, where it associates with region-specific proteins, yielding complexes whose function is location specific. We herein investigated sodium channel remodeling within distinct cardiomyocyte microdomains during heart failure. METHODS AND RESULTS:Mice were subjected to 6 weeks of transverse aortic constriction (TAC; n=32) to induce heart failure. Sham-operated on mice were used as controls (n=20). TAC led to reduced left ventricular ejection fraction, QRS prolongation, increased heart mass, and upregulation of prohypertrophic genes. Whole-cell sodium current (INa) density was decreased by 30% in TAC versus sham-operated on cardiomyocytes. On macropatch analysis, INa in TAC cardiomyocytes was reduced by 50% at the lateral membrane (LM) and by 40% at the intercalated disc. Electron microscopy and scanning ion conductance microscopy revealed remodeling of the intercalated disc (replacement of [inter-]plicate regions by large foldings) and LM (less identifiable T tubules and reduced Z-groove ratios). Using scanning ion conductance microscopy, cell-attached recordings in LM subdomains revealed decreased INa and increased late openings specifically at the crest of TAC cardiomyocytes, but not in groove/T tubules. Failing cardiomyocytes displayed a denser, but more stable, microtubule network (demonstrated by increased α-tubulin and Glu-tubulin expression). Superresolution microscopy showed reduced average NaV1.5 cluster size at the LM of TAC cells, in line with reduced INa. CONCLUSIONS:Heart failure induces structural remodeling of the intercalated disc, LM, and microtubule network in cardiomyocytes. These adaptations are accompanied by alterations in NaV1.5 clustering and INa within distinct subcellular microdomains of failing cardiomyocytes.
journal_name
J Am Heart Assocjournal_title
Journal of the American Heart Associationauthors
Rivaud MR,Agullo-Pascual E,Lin X,Leo-Macias A,Zhang M,Rothenberg E,Bezzina CR,Delmar M,Remme CAdoi
10.1161/JAHA.117.007622subject
Has Abstractpub_date
2017-12-08 00:00:00issue
12issn
2047-9980pii
JAHA.117.007622journal_volume
6pub_type
杂志文章abstract:BACKGROUND:Currently, acute ischemic stroke is still a leading cause of mortality and morbidity. Approximately 2 years ago, mechanical thrombectomy was proven beneficial as a revolutionary new therapy for stroke in the MR-CLEAN trial (A Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic ...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章,多中心研究
doi:10.1161/JAHA.118.008563
更新日期:2018-06-22 00:00:00
abstract:BACKGROUND:Bypass grafting remains the standard of care for coronary artery disease and severe lower extremity ischemia. Efficacy is limited by poor long-term venous graft patency secondary to intimal hyperplasia (IH) caused by venous injury upon exposure to arterial pressure. We investigate whether photochemical tissu...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.116.003856
更新日期:2016-07-27 00:00:00
abstract:BACKGROUND:Acute end points of catheter ablation for ventricular tachycardia (VT) remain incompletely defined. The aim of this study is to identify causes for failure in patients with structural heart disease and to assess the relation of this acute outcome to longer-term management and outcomes. METHODS AND RESULTS:F...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.113.000072
更新日期:2013-05-31 00:00:00
abstract::Background We aimed to determine the change in treatment strategies and times to treatment over the first 5 years of the Mission: Lifeline program. Methods and Results We assessed pre- and in-hospital care and outcomes from 2008 to 2012 for patients with ST -segment-elevation myocardial infarction at US hospitals, usi...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章,多中心研究
doi:10.1161/JAHA.118.008096
更新日期:2019-01-08 00:00:00
abstract::Background Gait speed is a reliable measure of physical function and frailty in patients with aortic stenosis undergoing transcatheter aortic valve replacement (TAVR). Slow gait speed pre-TAVR predicts worse clinical outcomes post-TAVR. The consequences of improved versus worsened physical function post-TAVR are unkno...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.120.017075
更新日期:2020-09-01 00:00:00
abstract::Background Although PAR-1 (protease-activated receptor-1) exerts important functions in the pathophysiology of the cardiovascular system, the role of PAR-1 signaling in heart failure development remains largely unknown. We tested the hypothesis that PAR-1 signaling inhibition has protective effects on the progression ...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.119.015616
更新日期:2020-06-16 00:00:00
abstract::See Article Ramkumar et al. ...
journal_title:Journal of the American Heart Association
pub_type: 评论,社论
doi:10.1161/JAHA.119.013813
更新日期:2019-09-03 00:00:00
abstract:BACKGROUND:Cardiovascular disease in women often develops without conventional risk factors. Prenatal loss is a common pregnancy outcome that may result in physiological changes can increase the potential future risk of cardiovascular disease. Insufficient information exists regarding the impact of pregnancy loss on ea...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.117.007582
更新日期:2018-01-13 00:00:00
abstract:BACKGROUND:Cardiac fibrosis occurs because of disruption of the extracellular matrix network leading to myocardial dysfunction. Angiotensin II has been implicated in the development of cardiac fibrosis. Recently, microRNAs have been identified as an attractive target for therapeutic intervention in cardiac pathologies;...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.117.006763
更新日期:2017-11-07 00:00:00
abstract:BACKGROUND:Bromocriptine-QR (a quick-release formulation of bromocriptine mesylate), a dopamine D2 receptor agonist, is a US Food and Drug Administrration-approved treatment for type 2 diabetes mellitus (T2DM). A 3070-subject randomized trial demonstrated a significant, 40% reduction in relative risk among bromocriptin...
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.112.002279
更新日期:2012-10-01 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:Acute kidney injury (AKI) following primary percutaneous coronary intervention (pPCI) is frequently interpreted as contrast-induced AKI but may result from other insults. We aimed to determine the causal association of contrast material exposure and the incidence of AKI following pPCI using a control group o...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.117.005715
更新日期:2017-06-24 00:00:00
abstract::Background Healthcare disparities for psychiatric patients are common. Whether these inequalities apply to postresuscitation management in out-of-hospital cardiac arrest (OHCA) is unknown. We investigated differences in in-hospital cardiovascular procedures following OHCA between patients with and without psychiatric ...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.119.012708
更新日期:2019-08-20 00:00:00
abstract::Background This study examined the association between ideal cardiovascular health ( CVH ) and the retinal microvasculature in midadulthood. Methods and Results The Cardiovascular Risk in Young Finns Study included children from 5 Finnish University cities, who were chosen randomly from the national population registe...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章,多中心研究
doi:10.1161/JAHA.118.009487
更新日期:2018-10-16 00:00:00
abstract:BACKGROUND:Acute kidney injury (AKI) is a major risk factor for the development of chronic kidney disease. Nuclear factor-κB is a nuclear transcription factor activated post-ischemia, responsible for the transcription of proinflammatory proteins. The role of nuclear factor-κB in the renal fibrosis post-AKI is unknown. ...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.116.005092
更新日期:2017-07-03 00:00:00
abstract:BACKGROUND:Clinical guidelines recommend using predicted atherosclerotic cardiovascular disease (ASCVD) risk to inform treatment decisions. The objective was to compare the contribution of changes in modifiable risk factors versus aging to the development of high 10-year predicted ASCVD risk. METHODS AND RESULTS:A pro...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章,多中心研究
doi:10.1161/JAHA.116.005054
更新日期:2017-02-08 00:00:00
abstract::Background Obesity is a precursor to heart failure with preserved ejection fraction. Biomarkers that identify preclinical metabolic heart disease ( MHD ) in young obese patients would help identify high-risk individuals for heart failure prevention strategies. We assessed the predictive value of GAL3 (galectin-3), FST...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.118.011100
更新日期:2019-04-02 00:00:00
abstract:BACKGROUND:Diabetes is associated with coronary arteriolar endothelial dysfunction. We investigated the role of the small/intermediate (SK(Ca)/IK(Ca)) conductance of calcium-activated potassium channels in diabetes-related endothelial dysfunction. METHODS AND RESULTS:Coronary arterioles (80 to 150 μm in diameter) were...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.115.002062
更新日期:2015-08-24 00:00:00
abstract:BACKGROUND:Single-electrode ablation of the main renal artery for renal sympathetic denervation showed mixed blood pressure (BP)-lowering effects. Further improvement of the technique seems crucial to optimize effectiveness of the procedure. Because sympathetic nerve fibers are closer to the lumen in the distal part of...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章,多中心研究
doi:10.1161/JAHA.117.006196
更新日期:2017-08-10 00:00:00
abstract:BACKGROUND:Black race has been shown to be a risk factor for amputation in peripheral artery disease (PAD); however, race has been argued to be a marker for socioeconomic status (SES) rather than true disparity. The aim of this study is to study the impact of race and SES on amputation risk in PAD patients. METHODS AN...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.117.007425
更新日期:2018-01-12 00:00:00
abstract::Background Ankle-brachial indexes (ABI) are a noninvasive diagnostic tool for peripheral arterial disease and a marker of increased cardiovascular risk. ABI is calculated using the highest systolic blood pressure of the 4 ankle arteries (bilateral dorsalis pedis and posterior tibial). Accordingly, patients may be assi...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.119.015398
更新日期:2020-06-02 00:00:00
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 act...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.117.005537
更新日期:2017-07-11 00:00:00
abstract::Background The "healthy obese" hypothesis suggests the risks associated with excess adiposity are reduced in those with higher muscle quality (mass/strength). Alternative possibilities include loss of muscle quality as people become unwell (reverse causality) or unmeasured confounding. Methods and Results We conducted...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.118.011638
更新日期:2019-07-02 00:00:00
abstract:BACKGROUND:NO bioavailability has not been systematically examined in congenital heart disease (CHD). To assess NO in patients with CHD, we measured nasal NO (nNO) generated by the nasal epithelia, given blood NO is difficult to measure (half-life, <2 ms). Given NO's role in hemodynamic regulation and the association o...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.117.007447
更新日期:2017-12-06 00:00:00
abstract:BACKGROUND:The natural history of coronary artery aneurysms (CAA) after intravenous immunoglobulin (IVIG) treatment in the United States is not well described. We describe the natural history of CAA in US Kawasaki disease (KD) patients and identify factors associated with major adverse cardiac events (MACE) and CAA reg...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.116.003289
更新日期:2016-09-15 00:00:00
abstract::Background Duchenne muscular dystrophy (DMD) is a neuromuscular disorder caused by mutations within the dystrophin gene. DMD is characterized by progressive skeletal muscle degeneration and atrophy and progressive cardiomyopathy. It has been observed the severity of cardiomyopathy varies in patients with DMD. Methods ...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.120.016799
更新日期:2020-10-20 00:00:00
abstract::Background Some, but not all, studies report associations between shift work and hypertension, suggesting that particular subgroups may be at risk. We examined moderating effects of sleep duration and circadian preference on the relationship between shift work and new blood pressure (BP) medicine use at follow-up. Met...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章,多中心研究
doi:10.1161/JAHA.119.013269
更新日期:2019-10-15 00:00:00
abstract:BACKGROUND:Metropolitan versus nonmetropolitan status and area median income may independently affect care for and outcomes of acute coronary syndromes. We sought to determine whether location of care modifies the association among area income, receipt of cardiac catheterization, and mortality following an acute corona...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.115.002447
更新日期:2016-02-23 00:00:00
abstract:BACKGROUND:Though left ventricular mass (LVM) predicts cardiovascular events (CVD) and mortality in African Americans, limited data exists on factors contributing to change in LVM and its prognostic significance. We hypothesized that baseline blood pressure (BP) and body mass index (BMI) and change in these variables o...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.114.001224
更新日期:2015-02-05 00:00:00
abstract::Background Ischemic heart disease continues to be a leading cause of mortality in patients. Extracellular vesicles (EVs) provide a potential for treatment that may induce collateral vessel growth to increase myocardial perfusion. Methods and Results Nineteen male Yorkshire pigs were given a high-fat diet for 4 weeks, ...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.119.012617
更新日期:2019-08-06 00:00:00