Abstract:
:Current pharmacologic therapy for ischemic heart disease suffers multiple limitations such as compliance issues and side effects of medications. Revascularization procedures often end with need for repeat procedures. Patients remain symptomatic despite maximal medical therapy. Gene therapy offers an attractive alternative to current pharmacologic therapies and may be beneficial in refractory disease. Gene therapy with isoforms of growth factors such as VEGF, FGF and HGF induces angiogenesis, decreases apoptosis and leads to protection in the ischemic heart. Stem cell therapy augmented with gene therapy used for myogenesis has proven to be beneficial in numerous animal models of myocardial ischemia. Gene therapy coding for antioxidants, eNOS, HSP, mitogen-activated protein kinase and numerous other anti apoptotic proteins have demonstrated significant cardioprotection in animal models. Clinical trials have demonstrated safety in humans apart from symptomatic and objective improvements in cardiac function. Current research efforts are aimed at refining various gene transfection techniques and regulation of gene expression in vivo in the heart and circulation to improve clinical outcomes in patients that suffer from ischemic heart disease. In this review article we will attempt to summarize the current state of both preclinical and clinical studies of gene therapy to combat myocardial ischemic disease. This article is part of a Special Section entitled "Special Section: Cardiovascular Gene Therapy".
journal_name
J Mol Cell Cardioljournal_title
Journal of molecular and cellular cardiologyauthors
Lavu M,Gundewar S,Lefer DJdoi
10.1016/j.yjmcc.2010.06.007subject
Has Abstractpub_date
2011-05-01 00:00:00pages
742-50issue
5eissn
0022-2828issn
1095-8584pii
S0022-2828(10)00244-0journal_volume
50pub_type
杂志文章,评审abstract::Changes in the capacities of ATP-synthesizing reactions were analysed in residual non-infarcted myocardium following myocardial infarction. Rats were subjected to left coronary artery ligation (MI; n = 11) or to sham operation (sham; n = 18). Two months later, hearts were excised, rinsed and buffer-perfused isovolumic...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1996.0143
更新日期:1996-07-01 00:00:00
abstract::Endothelin-1 (ET-1) is a potent agonist of cell growth that also stimulates Na(+)/H(+) exchanger isoform 1 (NHE-1) activity. It was hypothesized that the increase in intracellular Na(+) ([Na(+)](i)) mediated by NHE-1 activity may induce the reverse mode of Na(+)/Ca(2+) exchanger (NCX(rev)) increasing intracellular Ca(...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2006.05.016
更新日期:2006-11-01 00:00:00
abstract::Recent work has highlighted the role of NR4A receptors in atherosclerosis and inflammation. In vascular smooth muscle cell (VSMC) proliferation, however, NOR-1 (neuron-derived orphan receptor-1) exerts antagonistic effects to Nur77 and Nurr1. The aim of this study was to analyse the effect of NOR-1 in VSMC inflammator...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2014.12.015
更新日期:2015-03-01 00:00:00
abstract:AIMS:Biglycan, a small leucine-rich proteoglycan, has been shown to play an important role in stabilizing fibrotic scars after experimental myocardial infarction. However, the role of biglycan in the development and regression of cardiomyocyte hypertrophy and fibrosis during cardiac pressure overload and unloading rema...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2016.10.011
更新日期:2016-12-01 00:00:00
abstract:UNLABELLED:Discrepant results for the phenotype of mitochondrial creatine kinase knockout mice (Mt-CK(-/-)) could be due to mixed genetic background and use of non-littermate controls. We therefore backcrossed with C57BL/6J for >8 generations, followed by extensive in vivo cardiac phenotyping. Echocardiography and in v...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2008.09.710
更新日期:2009-01-01 00:00:00
abstract::Fibroblast growth factor receptor (FGFR) is expressed in a variety of cells and is involved in their proliferation/migration/survival. To elucidate FGFR-mediated specific action of vascular endothelial cells (ECs) on myocardial ischemia, we generated endothelium-targeted transgenic mice overexpressing constitutively a...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2009.01.015
更新日期:2009-05-01 00:00:00
abstract::Congenital heart block (CHB) affects offspring of mothers with autoantibodies (positive IgG) to intracellular SSA/Ro and SSB/La ribonucleoproteins and is associated with high morbidity and mortality. Here, we show that maternal anti-Ro/La antibodies immunoreact with human fetal cardiomyocyte sarcolemma, recognize huma...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.2001.1379
更新日期:2001-06-01 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::There is increasing momentum toward the development of gene therapy for heart failure (HF) that is defined by impaired calcium (Ca2+) transport and reduced contractility. We have used FRET (fluorescence resonance energy transfer) between fluorescently-tagged SERCA2a (the cardiac Ca2+ pump) and PLB (phospholamban, vent...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2019.11.147
更新日期:2020-01-01 00:00:00
abstract::In mammalian myocardium, muscle contraction is regulated by the rapid release of Ca2+ ions through ryanodine-sensitive Ca2+ release channels present in the intracellular membrane compartment, sarcoplasmic reticulum (SR). In this study, the effects of regional ischemia on intrinsic SR Ca2+ release channel function were...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/0022-2828(92)93181-i
更新日期:1992-10-01 00:00:00
abstract::Inflammatory mediators have been implicated as a cause of reversible myocardial depression in septic shock. We previously reported that the release of lysozyme-c (Lmz-S) from leukocytes from the spleen or other organs contributes to myocardial dysfunction in Escherichia coli septic shock in dogs by binding to a cardia...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2005.06.009
更新日期:2005-10-01 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::Changes in the nonischemic remote myocardium of the heart contribute to left ventricular dysfunction after ischemia and reperfusion (I/R). Understanding the underlying mechanisms early after I/R is crucial to improve the adaptation of the viable myocardium to increased mechanical demands. Here, we investigated the rol...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2018.04.004
更新日期:2018-06-01 00:00:00
abstract::Myocardial infarction (MI) provokes regional inflammation which facilitates the healing, whereas excessive inflammation leads to adverse cardiac remodelling. Our aim was to determine the role of macrophage migration inhibitory factor (MIF) in inflammation and cardiac remodelling following MI. Wild type (WT) or global ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2014.01.015
更新日期:2014-04-01 00:00:00
abstract::Estrogen receptor alpha (ERalpha) is present in the heart consistent with estrogen-induced modulation of cardiac function by genomic and non-genomic mechanisms, and with estrogen-mediated cardioprotective effects. We show that, in heart from adult male rats, ERalpha is detected mainly as two distinct isoforms: (i) a a...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2006.05.022
更新日期:2006-09-01 00:00:00
abstract::Experimental evidence has emerged that myocardial ischemic preconditioning can prime the mitochondria into a "stress-resistant state", so that cell death is reduced following prolonged severe ischemia and reperfusion. Using a swine model of chronically ischemic myocardium, we tested the hypothesis that mitochondria wi...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2006.07.008
更新日期:2006-12-01 00:00:00
abstract::We tested the hypothesis that the early action potential shortening induced by hypoxia in perfused hearts is attributable to chloride currents activated or modulated by endogenous catecholamine release. Rabbit hearts perfused at 33 degrees C and paced at 2.5-2.8 Hz were used for membrane potential recordings with micr...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1996.0026
更新日期:1996-02-01 00:00:00
abstract::Mitochondria are the major source of cellular energy (ATP), as well as critical mediators of widespread functions such as cellular redox balance, apoptosis, and metabolic flux. The organelles play an especially important role in the maintenance of cardiac homeostasis; their inability to generate ATP following impairme...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2020.03.011
更新日期:2020-05-01 00:00:00
abstract::Gain- and loss-of-function strategies using transgenic over-expression and targeted ablation of candidate genes in in the mouse have provided important mechanistic insights into cardiovascular development, physiology and disease. An essential, but challenging step is the functional analysis of the resultant phenotype....
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章,评审
doi:10.1006/jmcc.2000.1294
更新日期:2001-01-01 00:00:00
abstract::Calmodulin (CaM) is a Ca-binding protein that binds to, and can directly inhibit cardiac ryanodine receptor calcium release channels (RyR2). Animal studies have shown that RyR2 hyperphosphorylation reduces CaM binding to RyR2 in failing hearts, but data are lacking on how CaM regulates human RyR2 and how this regulati...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2019.03.018
更新日期:2019-05-01 00:00:00
abstract::The opening of mitochondrial permeability transition pore (PTP) during reperfusion injury of heart has been well demonstrated and thus controlling PTP would attenuate the myocardial damage and cell death. Ursodeoxycholic acid (UDCA) is a hydrophilic bile salt and has been shown to prevent apoptosis in hepatocytes by i...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2005.07.014
更新日期:2005-11-01 00:00:00
abstract::Duchenne Muscular Dystrophy (DMD) cardiomyopathy is a progressive lethal disease caused by the lack of the dystrophin protein in the heart. The most widely used animal model of DMD is the dystrophin-deficient mdx mouse; however, these mice exhibit a mild dystrophic phenotype with heart failure only late in life. In co...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2017.06.004
更新日期:2017-07-01 00:00:00
abstract::The progression of cardiomyopathy to congestive heart failure is often associated with the expression of fetal cardiac-specific genes. In mice, the basic helix-loop-helix transcription factors, dHAND and eHAND, are expressed in a cardiac chamber-specific fashion and are essential for fetal cardiac development, but are...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.2001.1434
更新日期:2001-09-01 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::The aim of this study was to determine if embryonic stem cell derived cardiomyocyte aggregates (ESdCs) can act as pacemakers in spontaneously active cardiomyocyte preparations when their connexin isoform expression is tuned toward a more sinus nodal phenotype. Using microelectrode array recordings (MEAs), we demonstra...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2008.08.013
更新日期:2008-11-01 00:00:00
abstract::We examined changes in expression and function of the cardiac Na+, K(+)-pump in a post-infarction rat model of hypertrophy and congestive heart failure (CHF). Myocardial infarction was induced by ligation of the left coronary artery in Wistar rats and hearts were obtained from animals with CHF and from sham operated r...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1998.0696
更新日期:1998-07-01 00:00:00
abstract:BACKGROUNDS:Low serum cholesterol levels are associated with cardiac arrhythmias and poor prognosis in patients with chronic heart failure. However, the underlying mechanisms by which decreases in cholesterol content lead to cardiac dysfunction remain unclear. Multiple studies have implicated damage to cardiac transver...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2016.05.013
更新日期:2016-08-01 00:00:00
abstract::Endothelial dysfunction is the earliest pathologic alteration in diabetic vascular injury and plays a critical role in the development of atherosclerosis. Plasma levels of adiponectin (APN), a novel vasculoprotective adipocytokine, are significantly reduced in diabetic patients, but its relationship with endothelial d...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2008.10.014
更新日期:2009-03-01 00:00:00
abstract::Heart rate in mammals is inversely related to body weight. In the etruscan shrew it exceeds 960 beats/min. Since the heart depends primarily on energy from aerobic sources, it was interesting to examine some morphological parameters of the mitochondria in some mammals with a high heart frequency. Volume fraction and s...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/s0022-2828(85)80031-6
更新日期:1985-06-01 00:00:00
abstract::Reoxygenation of isolated rat cardiac myocytes following a period of hypoxia and substrate deprivation resulted in a 1.5-2-fold increase in the total Ca2+ content which could be inhibited by 1 microM antimycin A or ruthenium red (50% inhibition at 2.5 microM). This increase in Ca2+ content was not accompanied by any r...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/0022-2828(89)90795-5
更新日期:1989-10-01 00:00:00