Abstract:
:Background We aim to generate a line of "universal donor" human induced pluripotent stem cells (hi PSC s) that are nonimmunogenic and, therefore, can be used to derive cell products suitable for allogeneic transplantation. Methods and Results hi PSC s carrying knockout mutations for 2 key components (β2 microglobulin and class II major histocompatibility class transactivator) of major histocompatibility complexes I and II (ie, human leukocyte antigen [HLA] I/ II knockout hi PSC s) were generated using the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR associated protein 9 (Cas9) gene-editing system and differentiated into cardiomyocytes. Pluripotency-gene expression and telomerase activity in wild-type ( WT ) and HLAI / II knockout hi PSC s, cardiomyocyte marker expression in WT and HLAI / II knockout hi PSC -derived cardiomyocytes, and assessments of electrophysiological properties (eg, conduction velocity, action-potential and calcium transient half-decay times, and calcium transient increase times) in spheroid-fusions composed of WT and HLAI / II knockout cardiomyocytes, were similar. However, the rates of T-cell activation before (≈21%) and after (≈24%) exposure to HLAI / II knockout hi PSC -derived cardiomyocytes were nearly indistinguishable and dramatically lower than after exposure to WT hi PSC -derived cardiomyocytes (≈75%), and when WT and HLAI / II knockout hi PSC -derived cardiomyocyte spheroids were cultured with human peripheral blood mononuclear cells, the WT hi PSC -derived cardiomyocyte spheroids were smaller and displayed contractile irregularities. Finally, expression of HLA -E and HLA -F was inhibited in HLAI / II knockout cardiomyocyte spheroids after coculture with human peripheral blood mononuclear cells, although HLA -G was not inhibited; these results are consistent with the essential role of class II major histocompatibility class transactivator in transcriptional activation of the HLA -E and HLA-F genes, but not the HLA -G gene. Expression of HLA -G is known to inhibit natural killer cell recognition and killing of cells that lack other HLAs. Conclusions HLAI / II knockout hi PSC s can be differentiated into cardiomyocytes that induce little or no activity in human immune cells and, consequently, are suitable for allogeneic transplantation.
journal_name
J Am Heart Assocjournal_title
Journal of the American Heart Associationauthors
Mattapally S,Pawlik KM,Fast VG,Zumaquero E,Lund FE,Randall TD,Townes TM,Zhang Jdoi
10.1161/JAHA.118.010239subject
Has Abstractpub_date
2018-12-04 00:00:00pages
e010239issue
23issn
2047-9980journal_volume
7pub_type
杂志文章abstract:BACKGROUND:Quercetin, the most abundant dietary flavonol, has antioxidant effects in cardiovascular disease, but the evidence regarding its effects on blood pressure (BP) has not been conclusive. We assessed the impact of quercetin on BP through a systematic review and meta-analysis of available randomized controlled t...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章,meta分析,评审
doi:10.1161/JAHA.115.002713
更新日期:2016-07-12 00:00:00
abstract::Background Many observational studies and trials have shown that coronary artery bypass grafting improves the survival in patients with ischemic cardiomyopathy. However, these results are based on data generated from developed countries. Poor socioeconomic statuses, lack of uniformity in healthcare delivery, differenc...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.118.010225
更新日期:2019-05-21 00:00:00
abstract:BACKGROUND:The 4-variable risk score from University of California, Los Angeles (UCLA) demonstrated superior discrimination in advanced heart failure, compared to established risk scores. However, the model has not been externally validated, and its suitability as a selection tool for heart transplantation (HT) and lef...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.114.000998
更新日期:2014-06-06 00:00:00
abstract:BACKGROUND:Hemorrhagic risk assessment is a crucial issue in patients with nonvalvular atrial fibrillation (NVAF) who are receiving oral anticoagulant therapy (OAT). Our aim was to analyze the relationship between vitamin E, which possesses anticoagulant properties, and bleeding events in NVAF patients. METHODS AND RE...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.113.000364
更新日期:2013-10-28 00:00:00
abstract:BACKGROUND:Adults with repaired coarctation of the aorta (CoA) have reduced long-term survival compared with the general population. This study aimed to determine whether CoA is independently associated with premature ischemic and hemorrhagic stroke in the contemporary era. METHODS AND RESULTS:This was a cross-section...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章,多中心研究
doi:10.1161/JAHA.118.009072
更新日期:2018-06-01 00:00:00
abstract:BACKGROUND:Galectin-3 (Gal-3) participates in different mechanisms involved in atherothrombosis, such as inflammation, proliferation, or macrophage chemotaxis. Thus, there have been committed intensive efforts to elucidate the function of Gal-3 in cardiovascular (CV) diseases. The role of Gal-3 as a circulating biomark...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.114.000785
更新日期:2014-08-05 00:00:00
abstract:BACKGROUND:Conflicting findings of the association between serum uric acid (UA) and stroke have been reported in both men and women, and it is unclear whether this association was different between men and women. We preformed this meta-analysis to assess the sex-specific effect of serum UA on the risk of stroke and its...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章,meta分析,评审
doi:10.1161/JAHA.116.005042
更新日期:2017-03-29 00:00:00
abstract:BACKGROUND:Platelet activation can lead to enhanced oxidative stress, inflammatory response, and endothelial dysfunction. To quantify the effects of platelet inhibition on endothelial function, we assessed platelet activity of healthy persons before and after clopidogrel administration and evaluated its effects on endo...
journal_title:Journal of the American Heart Association
pub_type: 临床试验,杂志文章
doi:10.1161/JAHA.116.003751
更新日期:2016-10-31 00:00:00
abstract:BACKGROUND:Preeclampsia (PE) is a life-threatening hypertensive disorder of pregnancy associated with autoantibodies, termed AT1-AA, that activate the AT1 angiotensin receptor. Although the pathogenic nature of these autoantibodies has been extensively studied, little is known about the molecular cause of their generat...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.115.002323
更新日期:2015-12-16 00:00:00
abstract:BACKGROUND:Fatty acids constitute the critical components of cell structure and function, and dysregulation of fatty acid composition may exert diverging vascular effects including proliferation, migration, and differentiation of vascular smooth muscle cells (VSMCs). However, direct evidence for this hypothesis has bee...
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
abstract:BACKGROUND:The aim of this study was to investigate whether the association between baseline cardiovascular health (CVH) and incident cardiovascular disease differs according to coronary heart disease (CHD) and stroke subtypes, and to assess the mediating effect of inflammatory and hemostatic blood biomarkers. METHODS...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章,多中心研究
doi:10.1161/JAHA.117.006389
更新日期:2017-10-17 00:00:00
abstract::Background Antazoline mesylate represents an antihistamine capable of rapid and safe cardioversion of atrial fibrillation, yet evidence concerning its efficacy in comparison to other medications is insufficient. The study aimed to evaluate the success rate and safety of pharmacological cardioversion of atrial fibrilla...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.118.010153
更新日期:2018-10-16 00:00:00
abstract::Background Pharmacists-led medication reviews (MRs) are claimed to be effective for the control of cardiovascular diseases; however, the evidence in the literature is conflicting. The main objective of this meta-analysis was to analyze the impact of pharmacist-led MRs on cardiovascular disease risk factors overall and...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章,meta分析
doi:10.1161/JAHA.119.013627
更新日期:2019-11-19 00:00:00
abstract:BACKGROUND:Extracellular fluid (ECF) excess is an independent predictor of cardiovascular morbidity in patients undergoing dialysis. This study aimed to investigate the relationship between ECF status, which is affected by renal function, and coronary artery calcification (CAC), which is a marker of cardiovascular dise...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.118.008935
更新日期:2018-06-30 00:00:00
abstract::Background Cardiovascular disease incidence, prevalence, morbidity, and mortality have declined in the past several decades; however, disparities persist among subsets of the population. Notably, blacks have not experienced the same improvements on the whole as whites. Furthermore, frequent reports of relatively poore...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.119.015247
更新日期:2020-05-05 00:00:00
abstract::Background Malnutrition is one of the most important comorbidities in patients with heart failure with preserved ejection fraction. We recently reported the prognostic significance of serum cholinesterase level and superior predictive power of cholinesterase level to other objective nutritional indices such as the con...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章,多中心研究
doi:10.1161/JAHA.119.014100
更新日期:2020-01-07 00:00:00
abstract::Background Atherosclerotic vertebrobasilar disease is a significant etiology of posterior circulation stroke. The prospective observational VERiTAS (Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke) study demonstrated that distal hemodynamic status is a robust predictor of subsequent ve...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.120.016406
更新日期:2020-06-16 00:00:00
abstract:BACKGROUND:Regression of left ventricular (LV) hypertrophy (LVH) has been a goal in clinical trials. This study tests the external validity of results of clinical trials on LVH regression using a large registry from a tertiary care center, to identify phenotypes less likely to achieve regression of LVH. METHODS AND RE...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.116.004152
更新日期:2017-03-08 00:00:00
abstract:BACKGROUND:Magnesium is associated with lower risk of sudden cardiac death, possibly through antiarrhythmic mechanisms. Magnesium influences endothelial function, inflammation, blood pressure, and diabetes, but a direct relation with coronary heart disease (CHD) risk has not been established. METHODS AND RESULTS:We pr...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.113.000114
更新日期:2013-03-18 00:00:00
abstract:BACKGROUND:Microvascular injury (MVI) after primary percutaneous coronary intervention for ST-elevation myocardial infarction (STEMI) is a major determinant of adverse clinical outcome. Experimental data indicate an impact of hypercholesterolemia on MVI; however, there is a lack of clinical studies confirming this rela...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.117.006957
更新日期:2017-10-10 00:00:00
abstract:BACKGROUND:Morphine is commonly used to treat chest pain during myocardial infarction, but its effect on cardiovascular outcome has never been directly evaluated. The aim of this study was to examine the effect and safety of morphine in patients with acute anterior ST-segment elevation myocardial infarction followed up...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.117.006833
更新日期:2018-02-10 00:00:00
abstract::See Editorial by Cenko et al. ...
journal_title:Journal of the American Heart Association
pub_type: 评论,社论
doi:10.1161/JAHA.118.011835
更新日期:2019-02-19 00:00:00
abstract:BACKGROUND:Obesity is causally associated with atherosclerosis, and adipose tissue (AT)-derived exosomes may be implicated in the metabolic complications of obesity. However, the precise role of AT-exosomes in atherogenesis remains unclear. We herein aimed to assess the effect of AT-exosomes on macrophage foam cell for...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.117.007442
更新日期:2018-03-03 00:00:00
abstract:BACKGROUND:Few studies have examined the impact of lifecourse socioeconomic position (SEP) on cardiovascular disease (CVD) risk among African Americans. METHODS AND RESULTS:We used data from the Jackson Heart Study (JHS) to examine the associations of multiple measures of lifecourse SEP with CVD events in a large coho...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.114.001553
更新日期:2015-05-27 00:00:00
abstract:BACKGROUND:Greater understanding of differences between men and women with coronary heart disease is needed. METHODS AND RESULTS:In this post hoc analysis of the STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) trial, we described psychosocial factors, treatments, and outcomes of...
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.117.006695
更新日期:2017-09-14 00:00:00
abstract:BACKGROUND:Cryoballoon pulmonary vein isolation (PVI) has emerged as an alternative to radiofrequency PVI for atrial fibrillation (AF). Data are lacking to define the rates and predictors of complications, particularly phrenic nerve injury (PNI). METHODS AND RESULTS:We evaluated a single-center prospective registry of...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.116.003724
更新日期:2016-07-21 00:00:00
abstract:BACKGROUND:Data are limited regarding outcomes of deferred lesions in patients with angiographically insignificant stenosis but low fractional flow reserve (FFR). We investigated the natural history of angiographically insignificant stenosis with low FFR among patients who underwent routine 3-vessel FFR measurement. M...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章,多中心研究
doi:10.1161/JAHA.117.006071
更新日期:2017-08-22 00:00:00
abstract:BACKGROUND:CSL112 is a new formulation of human apolipoprotein A-I (apoA-I) being developed to reduce cardiovascular events following acute coronary syndrome. This phase 2a, randomized, double-blind, multicenter, dose-ranging trial represents the first clinical investigation to assess the safety and pharmacokinetics/ph...
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.115.002171
更新日期:2015-08-25 00:00:00
abstract:BACKGROUND:Epidemiological evidence suggests a cardioprotective role of α-linolenic acid (ALA), a plant-derived ω-3 fatty acid. It is unclear whether ALA is beneficial in a background of high marine ω-3 fatty acids (long-chain n-3 polyunsaturated fatty acids) intake. In persons at high cardiovascular risk from Spain, a...
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.115.002543
更新日期:2016-01-26 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