Abstract:
:Cell therapy has the potential to drastically improve clinical outcomes for the 1.45 million patients suffering from a myocardial infarction (MI) each year in the U.S. However, the limitations associated with this treatment - including poor engraftment, significant cell death and poor differentiation potential - have prevented its widespread application clinically. To optimize functional improvements provided by transplanted cells, there is a need to develop methods that increase cellular retention and viability, while supporting differentiation and promoting paracrine signaling. Current in vivo models are expensive, difficult to access and manipulate and are time consuming. We have developed an in vitro model of MI which allows for a straightforward, consistent and relatively accurate prediction of cell fate following injection in vivo. The model demonstrated how the infarct environment impairs cellular engraftment and differentiation, but identified an implantation strategy which enhanced cell fate in vitro. Multivariate linear regression identified variables within the model that regulated vascular differentiation potential including oxygen tension, stiffness and cytokine presence, while cardiac differentiation was more accurately predicted by Isl-1 expression in the original cell isolate than any other variable present within the model system. The model highlighted how the cells' sensitivity to the infarct variables varied from line to line, which emphasizes the importance of the model system for the prediction of cell fate on a patient specific basis. Further development of this model system could help predict the clinical efficacy of cardiac progenitor cell therapy at the patient level as well as identify the optimal strategy for cell delivery.
journal_name
J Mol Cell Cardioljournal_title
Journal of molecular and cellular cardiologyauthors
Sullivan KE,Burns LJ,Black LD 3rddoi
10.1016/j.yjmcc.2015.09.007subject
Has Abstractpub_date
2015-11-01 00:00:00pages
91-100eissn
0022-2828issn
1095-8584pii
S0022-2828(15)30060-2journal_volume
88pub_type
杂志文章abstract::The possible involvement of protein kinase C in modulating membrane currents was investigated in isolated guinea-pig ventricular cells. In a Na(+)-and K(+)-free external solution, the delayed rectifier K+ current (IK) was increased by the activator of protein kinase C (PKC), 12-O-tetradecanoylphorbol-13-acetate (TPA)....
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/0022-2828(90)91015-y
更新日期:1990-06-01 00:00:00
abstract::Vascular tone is regulated by a variety of neurotransmitters, vasoactive hormones and autacoids, and vasoactive drugs. These actions are mediated, at least in part, by actions on the membrane ion channels, exerted either directly or indirectly. In this article, we described evidence that four different protein kinase ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章,评审
doi:10.1016/s0022-2828(08)80009-0
更新日期:1995-01-01 00:00:00
abstract::Oxygen deprivation for prolonged periods leads to cardiac cell death and ventricular dysfunction. The ability to prevent myocardial cell death would be of significant therapeutic value in maintaining cardiac function after injury. While caspases have been suggested to play a critical role in apoptosis, their involveme...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1999.1057
更新日期:2000-01-01 00:00:00
abstract::Human vascular smooth muscle cells (HVSMCs) are resistant to Fas-mediated death under normal physiological conditions. However, HVSMC death by activation of the receptor pathway was reported in the atherosclerotic lesions. In this study, we investigated whether 7-ketocholesterol, one of the major cholesterol oxides in...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2005.07.018
更新日期:2005-11-01 00:00:00
abstract::We evaluated the hypothesis that uterine cells home to the heart after injury and improve cardiac outcomes. Premenopausal women have fewer cardiovascular complications than age-matched men, but the mechanisms responsible for this protection have not been conclusively identified. Hysterectomy was performed in young fem...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2012.03.002
更新日期:2012-06-01 00:00:00
abstract::We investigated whether parathyroid hormone-related peptide (PTH-rP), recently found expressed in the heart, exerts growth and contractile effects on adult cardiomyocytes from rat hearts. Synthetic PTH-rP peptides were used covering either a protein kinase C (PKC)-activating domain [PTH-rP(107-111)], or an adenylate c...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1997.0520
更新日期:1997-11-01 00:00:00
abstract::Fibrosis, a consequence of tissue repair, can become a final common pathway to organ failure, if progressive. Prevention and regression of organ fibrosis represent targets of considerable interest. The natural fate of fibrosis differs among various tissues being either persistent, progressive or regressive. Cellular a...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1999.0944
更新日期:1999-05-01 00:00:00
abstract::The pyrimidine base, orotic acid (OA), improves the function of recently infarcted hearts subjected to global ischemia but its mechanism of action is unclear. Our aims were to examine (i) in normal rats, the effect of OA on pyrimidine levels in plasma, liver and heart; (ii) in rats with normal or infarcted hearts, the...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1997.0550
更新日期:1997-12-01 00:00:00
abstract::Cardiac tyhrotropin-releasing hormone (TRH) is overexpressed in the hypertrophied left ventricle (LV) of spontaneously hypertensive rats (SHR) and its inhibition prevents both hypertrophy and fibrosis. In a normal heart, the TRH increase induces fibrosis and hypertrophy opening the question of whether TRH could be a c...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2018.09.009
更新日期:2018-11-01 00:00:00
abstract::The endoplasmic reticulum (ER) forms discrete junctions with the plasma membrane (PM) that play a critical role in the regulation of Ca2+ signaling during cellular bioenergetics, apoptosis and autophagy. We have previously confirmed that acetylcholine can inhibit ER stress and apoptosis after inflammatory injury. Howe...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2017.04.001
更新日期:2017-06-01 00:00:00
abstract::RP58866 (1-[-2-(3,4-dihydro-2H-1-benzopyran-4-yl)ethyl]-4- (3,4-dimethoxyphenyl)-piperidine), a specific blocker of the inwardly rectifying K+ current (IK1), is an extremely effective antiarrhythmic agent in rat, rabbit and primate (marmoset) isolated hearts in the settings of acute ischaemia and reperfusion (Rees and...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1995.0046
更新日期:1995-12-01 00:00:00
abstract::The BH3-only proteins, including BNip3, are members of the Bcl-2 family of cell death-regulating factors. Whereas proteins such as Bax and Bak play a central role in most forms of apoptosis, the BH3-only proteins appear to modulate apoptosis through cell type- and signal-specific pathways. This review will focus on ou...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章,评审
doi:10.1016/j.yjmcc.2004.11.007
更新日期:2005-01-01 00:00:00
abstract::Atrial cardiac myocytes secrete the vasoactive hormone atrial natriuretic peptide (ANP) by both constitutive and regulated exocytotic fusion of ANP-containing large dense core vesicles (LDCV) with the sarcolemma. Detailed information, however, regarding the identity and function of specific membrane fusion proteins (S...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2005.12.007
更新日期:2006-03-01 00:00:00
abstract::During the past decade, the crucial role of microRNAs (miRs) controlling tissue homeostasis and disease in the cardiovascular system has become widely recognized. By controlling the expression levels of their targets, several miRs have been shown to modulate the function of endothelial cells, vascular smooth muscle ce...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章,评审
doi:10.1016/j.yjmcc.2014.10.021
更新日期:2015-12-01 00:00:00
abstract::We studied peripheral skeletal muscle metabolism in monocrotaline-treated rats. Two distinct groups emerged: a percentage of the animals developed ventricular hypertrophy, with no signs of heart failure (compensated group), whilst others, besides ventricular hypertrophy, developed the syndrome of congestive heart fail...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1996.0219
更新日期:1996-11-01 00:00:00
abstract::This paper examines the quantitative relationship between the expression of myosin heavy chain (MHC) and actin at both the levels of their mRNAs and their proteins. Explanted human left ventricle tissues were obtained from non-diseased (ND) individuals and from dilated cardiomyopathy (DCM) patients with terminally fai...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1996.0317
更新日期:1997-03-01 00:00:00
abstract::Ca(2+) overload and free-radical injury are two mutually non-exclusive phenomena suggested to cause myocardial ischemia-reperfusion (IR)-induced contractile dysfunction; however, the mechanisms underlying their effects are not clear. One possible mechanism is the proteolytic modification of proteins by Ca(2+)-dependen...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2004.04.009
更新日期:2004-07-01 00:00:00
abstract::Endothelial cells responses to a variety of agonists include release of endothelium dependent vasodilators, such as endothelium dependent relaxing factor (EDRF) and prostacyclin (PGI2). These substances act on vascular smooth muscle to cause relaxation and also have potent anti-aggregatory effects on platelets. A stud...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/0022-2828(89)90841-9
更新日期:1989-02-01 00:00:00
abstract::Cardiac myosin binding protein-C (cMyBP-C) has 11 immunoglobulin or fibronectin-like domains, C0 through C10, which bind sarcomeric proteins, including titin, myosin and actin. Using bacterial expressed mouse N-terminal fragments (C0 through C3) in an in vitro motility assay of myosin-generated actin movement and the ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2011.09.019
更新日期:2012-01-01 00:00:00
abstract:AIMS:During embryogenesis, the onset of circulatory blood flow generates a variety of hemodynamic forces which reciprocally induce changes in cardiovascular development and performance. It has been known for some time that these forces can be detected by as yet unknown mechanosensory systems which in turn promote cardi...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2020.03.013
更新日期:2020-06-01 00:00:00
abstract::The modulating effects of Ca2+ on single K+ channel currents in canine heart sarcoplasmic reticulum were studied using a planar lipid bilayer technique. The open-state probability and the unitary open-state current both decreased gradually as the Ca2+ concentration was reduced from pCa 3 to pCa 7.5. Each single-channe...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1994.1022
更新日期:1994-02-01 00:00:00
abstract::Human hearts with idiopathic dilated cardiomyopathy have diminished adenylate cyclase activity and increased amounts of the alpha-subunit of the inhibitory guanine nucleotide-binding regulatory protein (alpha Gi) as measured by pertussis toxin catalyzed ADP-ribosylation. We utilized specific antisera against synthetic...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/0022-2828(91)90168-l
更新日期:1991-04-01 00:00:00
abstract::Heat shock protein 70 (HSP70) has been shown to play a fundamental role in the induction of thermotolerance in many biological systems. Elevated synthesis of HSP70 in response to diverse stresses such as heat, anoxia, ischaemia, ethanol and heavy metals has been correlated with protection against subsequent more sever...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1994.1084
更新日期:1994-06-01 00:00:00
abstract::Diastolic dysfunction in the aging heart is a grave condition that challenges the life and lifestyle of a growing segment of our population. This report seeks to examine the role and interrelationship of inflammatory dysregulation in interstitial myocardial fibrosis and progressive diastolic dysfunction in aging mice....
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2010.10.019
更新日期:2011-01-01 00:00:00
abstract::The correlations between myocardial redox and energy states and atrial natriuretic peptide (ANP) secretion were studied in the perfused rat heart by exposing the hearts to global and low-flow ischemia for varying periods. Atrial and ventricular energy states and immunoreactive ANP in the effluent perfusate were measur...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/0022-2828(92)93155-d
更新日期:1992-02-01 00:00:00
abstract::We determined whether the dilated cardiomyopathy which develops between 30 and 140 days of age in the Syrian hamster strain MS200, before the onset of cardiac hypertrophy and failure, is associated with alterations in both the action potential (AP) and the Ca(2+)-independent transient outward current, Ito1. AP was rec...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1996.0036
更新日期:1996-02-01 00:00:00
abstract::With electrophysiological methods, mechanisms of the restorative action of coenzyme Q10 (CoQ10) in 2,4-dinitrophenol-depressed electrical and mechanical activities of isolated guinea-pig hearts were studied. Isoproterenol (3 X 10(-8) M)-induced action potential and contraction of the heart in 27 mM KCl Tyrode solution...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/0022-2828(83)90269-9
更新日期:1983-09-01 00:00:00
abstract:RATIONALE:Circulating monocytes play pivotal roles in chronic inflammatory diseases. Epoxyeicosatrienoic acids (EETs), metabolites of arachidonic acid, are known to have anti-inflammatory effects and are hydrolyzed by soluble epoxide hydrolase (sEH). OBJECTIVE:We aimed to investigate the effect of sEH inhibition in at...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2016.08.001
更新日期:2016-09-01 00:00:00
abstract::Aging enhances cardiac injury during ischemia and reperfusion compared to the adult heart, including in the Fischer 344 rat model of aging (F344). In interfibrillar cardiac mitochondria obtained from the elderly F344 rat, the rate of oxidative phosphorylation and the activity of electron transport complex III is decre...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2009.03.007
更新日期:2009-06-01 00:00:00
abstract::Cardiac troponin I (cTnI), the inhibitory-unit, and cardiac troponin T (cTnT), the tropomyosin-binding unit together with the Ca-binding unit (cTnC) of the hetero-trimeric troponin complex signal activation of the sarcomeres of the adult cardiac myocyte. The unique structure and heart myocyte restricted expression of ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章,评审
doi:10.1016/j.yjmcc.2020.05.010
更新日期:2020-06-01 00:00:00