Abstract:
BACKGROUND:Transcription of the myristoylated alanine-rich C kinase substrate (MARCKS) is upregulated in animal models of intimal hyperplasia. MARCKS knockdown inhibits vascular smooth muscle cell (VSMC) migration in vitro; however, the mechanism is as yet unknown. We sought to elucidate the mechanism of MARCKS-mediated motility and determine whether MARCKS knockdown reduces intimal hyperplasia formation in vivo. METHODS AND RESULTS:MARCKS knockdown blocked platelet-derived growth factor (PDGF)-induced translocation of cortactin to the cell cortex, impaired both lamellipodia and filopodia formation, and attenuated motility of human coronary artery smooth muscle cells (CASMCs). Activation of the small GTPases, Rac1 and Cdc42, was prevented by MARCKS knockdown. Phosphorylation of MARCKS resulted in a transient shift of MARCKS from the plasma membrane to the cytosol. MARCKS knockdown significantly decreased membrane-associated phosphatidylinositol 4,5-bisphosphate (PIP2) levels. Cotransfection with an intact, unphosphorylated MARCKS, which has a high binding affinity for PIP2, restored membrane-associated PIP2 levels and was indispensable for activation of Rac1 and Cdc42 and, ultimately, VSMC migration. Overexpression of MARCKS in differentiated VSMCs increased membrane PIP2 abundance, Rac1 and Cdc42 activity, and cell motility. MARCKS protein was upregulated early in the development of intimal hyperplasia in the murine carotid ligation model. Decreased MARKCS expression, but not total knockdown, attenuated intimal hyperplasia formation. CONCLUSIONS:MARCKS upregulation increases VSMC motility by activation of Rac1 and Cdc42. These effects are mediated by MARCKS sequestering PIP2 at the plasma membrane. This study delineates a novel mechanism for MARCKS-mediated VSMC migration and supports the rational for MARCKS knockdown to prevent intimal hyperplasia.
journal_name
J Am Heart Assocjournal_title
Journal of the American Heart Associationauthors
Yu D,Makkar G,Strickland DK,Blanpied TA,Stumpo DJ,Blackshear PJ,Sarkar R,Monahan TSdoi
10.1161/JAHA.115.002255subject
Has Abstractpub_date
2015-10-08 00:00:00pages
e002255issue
10issn
2047-9980pii
JAHA.115.002255journal_volume
4pub_type
杂志文章abstract:BACKGROUND:Treatment decisions for aortic valve replacement (AVR) should be sensitive to patient preferences. However, we lack knowledge of patient preferences and how to obtain them. METHODS AND RESULTS:We assessed the mortality risk patients were willing to accept when undergoing AVR by using the Standard Gamble met...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.115.002828
更新日期:2016-03-18 00:00:00
abstract::See Article Cammann et al. ...
journal_title:Journal of the American Heart Association
pub_type: 评论,社论
doi:10.1161/JAHA.119.013201
更新日期:2019-08-06 00:00:00
abstract:BACKGROUND:The mechanisms and relevance of impaired glucose homeostasis in advanced heart failure (HF) are poorly understood. The study goals were to examine glucose regulation, pancreatic endocrine function, and metabolic factors related to prognosis in patients with nondiabetic advanced HF. METHODS AND RESULTS:In to...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.116.005290
更新日期:2017-08-07 00:00:00
abstract::Background Circulating proteins are exposed to vascular endothelial layer and influence their functions. Among them, adipsin is a member of the trypsin family of peptidases and is mainly secreted from adipocytes, monocytes, and macrophages, catalyzing the rate-limiting step of the alternative complement pathway. Howev...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.119.013716
更新日期:2019-12-03 00:00:00
abstract::Background The ODYSSEY OUTCOMES (Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome) trial demonstrated that alirocumab reduced major cardiovascular events. However, because of the hierarchical testing strategy used for the multiple outcomes examined, the observed reduction in all-cause mortality was...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章,随机对照试验
doi:10.1161/JAHA.119.013170
更新日期:2019-10-15 00:00:00
abstract::Background Global fractional flow reserve (FFR) (ie, the sum of the FFR values in the 3 major coronary arteries) is a physiologic correlate of global atherosclerotic burden. The objective of the present study was to investigate the value of global FFR in predicting long-term clinical outcome of patients with stable co...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.120.017729
更新日期:2020-12-15 00:00:00
abstract::Background Previous studies have reported an association between the timing of menarche and cardiovascular disease ( CVD ). However, emerging studies have not examined the timing of menarche in relation to role of estrogen over a lifetime and major adverse cardiac events ( MACE ). Methods and Results A total of 648 wo...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.119.012406
更新日期:2019-06-18 00:00:00
abstract:BACKGROUND:Platelet-derived growth factor BB, a potent mitogen of pulmonary artery smooth muscle cells (PASMCs), has been implicated in pulmonary arterial remodeling, which is a key pathogenic feature of pulmonary arterial hypertension. Previous microRNA profiling in platelet-derived growth factor BB-treated PASMCs fou...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.117.007572
更新日期:2018-03-07 00:00:00
abstract::Background Angiotensin II type 1 receptor ( AT 1R) autoantibody ( AT 1- AA ) was first identified as a causative factor in preeclampsia. Unlike physiological ligand angiotensin II (Ang II ), AT 1- AA can induce vasoconstriction in a sustained manner, causing a series of adverse effects, such as vascular injury and poo...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.118.011179
更新日期:2019-03-19 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:Elevated serum phosphorus might aggravate the effect of hypertension on mortality. The objective of this study was to examine the joint effect of hypertension and serum phosphorus on the risk of mortality. METHODS AND RESULTS:A large prospective (n=15 833), population-based cohort of participants from the N...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.114.001706
更新日期:2015-05-20 00:00:00
abstract::Background Atrial fibrillation (AF) has been shown to be associated with an increased risk of dementia as well as Alzheimer disease in observational studies. Whether this association reflects causal association is still unclear. The purpose of this study was to examine the causal association of AF with Alzheimer disea...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.119.014889
更新日期:2020-01-21 00:00:00
abstract::Background NT-proBNP (N-terminal pro-B-type natriuretic peptide) improves the discriminatory ability of risk-prediction models in type 2 diabetes mellitus (T2DM) but is not yet used in clinical practice. We assessed the discriminatory strength of NT-proBNP by itself for death and cardiovascular events in high-risk pat...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.120.017462
更新日期:2020-10-20 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 Increased vagal modulation is a mechanism that may partially explain the protective effect of healthy lifestyles. However, it is unclear how healthy lifestyles relate to vagal regulation longitudinally. We prospectively examined associations between a comprehensive measure of 4 important lifestyle factors a...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.119.012420
更新日期:2019-10-01 00:00:00
abstract:BACKGROUND:Carotid atherosclerosis (CA) is a reflector of generalized atherosclerosis that is associated with systemic vascular disease. Data are limited on the epidemiology of carotid lesions in a large, nationally representative population sample. We aimed to evaluate the prevalence of CA detected by carotid ultrason...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章,多中心研究
doi:10.1161/JAHA.118.008701
更新日期:2018-04-05 00:00:00
abstract::We, the Editors of the Journal of the American Heart Association, sincerely regret the publication of the article "Diversity, Inclusion, and Equity: Evolution of Race and Ethnicity Considerations for the Cardiology Workforce in the United States of America From 1969 to 2019".1 We are aware that the publication of this...
journal_title:Journal of the American Heart Association
pub_type: 评论,杂志文章
doi:10.1161/JAHA.120.019307
更新日期:2020-10-20 00:00:00
abstract::Background Hyperkalemia can be harmful, but the effect of correcting hyperkalemia is sparsely studied. We used nationwide data to examine hyperkalemia follow-up in patients with hypertension. Methods and Results We identified 7620 patients with hypertension, who had the first plasma potassium measurement ≥4.7 mmol/L (...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.120.017087
更新日期:2020-12-15 00:00:00
abstract::Background Recent literature reports a strong thrombotic tendency in patients hospitalized for a coronavirus disease 2019 (COVID-19) infection. This characteristic is unusual and seems specific to COVID-19 infections, especially in their severe form. Viral infections can trigger acquired thrombophilia, which can then ...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.120.017773
更新日期:2020-11-03 00:00:00
abstract::Background Informed consent for acute myocardial infarction and stroke research is challenging. Time for enrollment decisions is limited, patients and family are usually stressed, and being asked to participate in research is often unexpected. Despite these barriers, patients and surrogates have reported a preference ...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.119.012599
更新日期:2019-11-19 00:00:00
abstract:BACKGROUND:Workforce experts predict a future shortage of cardiologists that is expected to impact rural areas more severely than urban areas. However, there is little research on how rural patients are currently served through clinical outreach. This study examines the impact of cardiology outreach in Iowa, a state wi...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.115.002909
更新日期:2016-06-30 00:00:00
abstract:BACKGROUND:To address the lack of knowledge regarding the long-term risk of intracranial hemorrhage (ICH) after acute myocardial infarction (AMI), the aims of this study were to: (1) investigate the incidence, time trends, and predictors of ICH in a large population within 1 year of discharge after AMI; (2) investigate...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.115.002290
更新日期:2015-12-11 00:00:00
abstract::Background This study was performed to characterize the metabolic, functional, and structural cardiac changes in a canine model of radiation-induced heart disease by serial in vivo imaging and ex vivo analyses. Methods and Results Thirty-six dogs were randomly assigned to control or irradiated groups at 3 time points ...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.120.016875
更新日期:2020-09-15 00:00:00
abstract:BACKGROUND:Depression is known to increase the risk of coronary artery disease, but few studies have evaluated the association between depression and peripheral artery disease (PAD). We examined the association of depression with PAD and evaluated potential mediators of this association. METHODS AND RESULTS:We used da...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.112.002667
更新日期:2012-08-01 00:00:00
abstract:BACKGROUND:Dyslipidemia is a major risk factor for cardiovascular events. The prognostic importance of lipoproteins in patients with atrial fibrillation is not well understood. We aimed to explore the association between apolipoprotein A1 (ApoA1) and B (ApoB) and cardiovascular events in patients with atrial fibrillati...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.117.007444
更新日期:2018-02-01 00:00:00
abstract::Background While high levels of lipids and lipid variability are established risk factors for atherosclerotic cardiovascular disease, their roles in the development of atrial fibrillation (AF) are unclear, with previous studies suggesting a "cholesterol paradox." Methods and Results A nationwide population-based cohor...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.119.012771
更新日期:2019-12-03 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
pub_type: 杂志文章
doi:10.1161/JAHA.119.013296
更新日期:2019-11-05 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:Patients with heart failure with preserved ejection fraction (HFpEF) exhibit a range of cardiovascular phenotypic profiles modified by several common comorbidities. In particular, patients with HFpEF tend to be older; however, it is unclear whether the effects of cardiovascular aging per se modify the expres...
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
abstract:BACKGROUND:Although clinical trials have proved that statin can be used prophylactically against cardiovascular events, the direct effects of statin on plaque development are not well understood. We generated low-density lipoprotein receptor knockout (LDLR(-/-)) pigs to study the effects of early statin administration ...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.115.002779
更新日期:2016-04-18 00:00:00