Abstract:
:Modification of gene expression in pulmonary arterial smooth muscle cells (PASMCs) could be a valuable tool for investigating the role of specific gene products in normal and pathological PASMC growth, and a novel potential therapy for pulmonary vascular diseases. To examine the direct role of fosB protein in PASMC growth, adenovirus (Ad) vectors were used to transfer sense or antisense full-length fosB cDNAs to cultured PASMCs to modify fosB expression, and investigate the effects of this modification on PASMC growth. The full-length fosB cDNA under the control of the cytomegalovirus (CMV) early gene promoter was constructed into an E1 region-deleted, replication-deficient human type 5 Ad vector in either sense or antisense orientation. Forty-eight hours after infection with the sense construct (Ad.S. fosB) at 3 plaque-forming units per cell (pfu/cell). PASMCs expressed abundant fosB mRNA and fosB protein. FosB protein was detected by immunohistochemistry in approximately 95% of the infected cells. PASMCs infected with Ad.S.fosB at ratios of 0.1, 0.2, 0.5, 1.3, and 10 pfu/cell showed a dose-dependent increase in fosB mRNA expression, with half-maximal and maximal expression at 1 and 10 pfu/cell, respectively. The increase in fosB mRNA expression was detected as early as 8 h and persisted for 25 days after infection. Forty-eight hours after infection with the antisense construct (Ad.A.fosB) at 3 pfu/cell, very low levels of fosB mRNA were detected by Northern blotting, in which the double-stranded fosB cDNA was labeled and used as a hybridization probe. FosB protein was undetectable by Western blotting or immunocytochemical analyses in the Ad.A.fosB infected cells. Cytopathical effects were observed when PASMCs were infected with either Ad.S.fosB or Ad.A.fosB at ratios of 10 pfu/cell or higher. Infection of serum-deprived PASMCs with Ad.S.fosB or Ad.A.fosB alone at 3 pfu/cell did not affect cellular growth. These results show that adenoviral vectors containing sense or antisense fosB cDNA expression units can be used to effectively modify fosB gene expression. Although changes in fos-B gene expression did not affect cellular growth, this model system offers a very effective method for elucidating the biological roles of other gene products and studying the pathways of PASMC gene regulation and signal transduction.
journal_name
J Mol Cell Cardioljournal_title
Journal of molecular and cellular cardiologyauthors
Lu CY,Giordano FJ,Rogers KC,Rothman Adoi
10.1006/jmcc.1996.0160subject
Has Abstractpub_date
1996-08-01 00:00:00pages
1703-13issue
8eissn
0022-2828issn
1095-8584pii
S0022-2828(96)90160-1journal_volume
28pub_type
杂志文章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::Diabetes is recognized as an independent risk factor for cardiovascular morbidity and mortality. This is due, in large part, to premature atherosclerosis, enhanced thrombogenicity and activation of systemic inflammatory programs with resultant vascular dysfunction. More enigmatic mechanisms underpinning diabetes-assoc...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章,评审
doi:10.1016/j.yjmcc.2009.02.001
更新日期:2009-06-01 00:00:00
abstract::Cardiac arrhythmias are one of the main causes of death worldwide. Several studies have shown that inflammation plays a key role in different cardiac diseases and Toll-like receptors (TLRs) seem to be involved in cardiac complications. In the present study, we investigated whether the activation of TLR4 induces cardia...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2014.08.012
更新日期:2014-11-01 00:00:00
abstract::Stress-induced regulation of the 72 kD heat shock protein (HSP 72), the major stress inducible protein in mammalian cells, is mediated by the activation and binding of a heat shock transcription factor (HSF) to a specific sequence in the 5' region of the promoter termed the heat shock element (HSE). In agreement with ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1996.0043
更新日期:1996-03-01 00:00:00
abstract::Introduced several decades ago, the dogma persists that ventricular myocytes are terminally differentiated cells and cardiac repair by myocyte regeneration is completely inhibited shortly after birth. On the basis that cardiac myocytes are unable to divide in the adult heart, myocyte growth under physiologic and patho...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章,评审
doi:10.1006/jmcc.2001.1506
更新日期:2002-02-01 00:00:00
abstract::Transforming growth beta-1 (TGF-beta1) appears to play a critical role in the regulation of arterial intimal growth and the development of atherosclerosis. TGF-beta1 is expressed at increased levels in diseased arteries; however, its role in disease development remains controversial. Experiments in which TGF-beta1 is ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2005.09.015
更新日期:2006-01-01 00:00:00
abstract::Lysophosphatidylcholine (LPC) accumulation in intracellular and/or interstitial space in cardiomyocytes may underlie as a mechanism for tachycardia and various arrhythmias during cardiac ischemia, which is usually accompanied by elevation of intracellular Ca(2+) concentration ([Ca(2+)](i)). The present study was there...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2009.08.032
更新日期:2010-01-01 00:00:00
abstract::Chronic pressure overload to the heart leads to cardiac hypertrophy and failure through processes that involve reorganization of subcellular compartments and alteration of established signaling mechanisms. To identify proteins contributing to this process, we examined changes in nuclear-associated myofilament proteins...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2010.02.009
更新日期:2010-06-01 00:00:00
abstract::In this article we review the late Na current which functionally can be measured using patch-clamp electrophysiology (INa,late). This current is largely enhanced under pathological myocardial conditions such as ischemia and heart failure. In addition, INa,late can cause systolic and diastolic contractile dysfunction v...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章,评审
doi:10.1016/j.yjmcc.2013.03.001
更新日期:2013-08-01 00:00:00
abstract::Cardiac myocytes have a high affinity. Mg(2+)-dependent, electrogenic, Na-inositol co-transporter on the plasma or sarcolemma (SL) membrane (Rubin and Hale, 1993). The ion specificity and stoichiometry of this transport process is unknown. Using bovine cardiac SL vesicles, we have determined that transmembrane movemen...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/0022-2828(95)90048-9
更新日期:1995-05-01 00:00:00
abstract::The polyunsaturated fatty acids (PUFAs) of the omega 3 series are known to modulate adrenergic functions in ventricular myocytes. This study evaluated the influence of hypoxia duration and PUFA composition on the ability of cultured rat cardiomyocytes in producing alpha- and beta-adrenergic messengers (IPs and cAMP). ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1998.0871
更新日期:1999-02-01 00:00:00
abstract::Titin is a very large alternatively spliced protein that performs multiple functions in heart and skeletal muscles. A rat strain is described with an autosomal dominant mutation that alters the isoform expression of titin. While wild type animals go through a developmental program where the 3.0 MDa N2B becomes the maj...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2008.02.272
更新日期:2008-06-01 00:00:00
abstract::Since ascorbate is unnecessary for cell growth and survival, cardiac fibroblasts are routinely cultured without it. However, ascorbate is necessary for optimal collagen synthesis, so we hypothesized that its presence would influence cell phenotype. Cardiac fibroblasts cultured without ascorbate had increased intracell...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2017.09.005
更新日期:2017-12-01 00:00:00
abstract::To determine whether catecholamines produce alterations in myocardial myosin-actin cycling kinetics, we investigated the effects of isoproterenol upon mechanical characteristics of constantly activated heart muscle thought to reflect crossbridge behavior. In isolated rabbit right ventricular papillary muscles in bariu...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/s0022-2828(88)80133-0
更新日期:1988-05-01 00:00:00
abstract:BACKGROUND:Pulmonary arterial hypertension (PAH) results in right ventricular (RV) failure, electro-mechanical dysfunction and heightened risk of sudden cardiac death (SCD), although exact mechanisms and predisposing factors remain unclear. Because impaired chronotropic response to exercise is a strong predictor of ear...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2018.11.017
更新日期:2019-02-01 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::Biglycan, a small dermatan sulphate proteoglycan, has been postulated to interact with other components of the extracellular matrix (ECM), specifically collagens. We hypothesized that biglycan messenger ribonucleic acid (mRNA) is increased in the myocardial infarct zone. Biglycan mRNA expression after acute myocardial...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1998.0737
更新日期:1998-09-01 00:00:00
abstract::The very low-density lipoprotein (VLDL) receptor is a member of the low-density lipoprotein (LDL) receptor gene family with distinct tissue distribution and function. VLDL receptors are also expressed in vascular smooth muscle cells (VSMCs) and have been shown to be upregulated in atherosclerotic lesions. In the prese...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2005.02.006
更新日期:2005-04-01 00:00:00
abstract::Our own previous ultrastructural studies in human hearts with dilated cardiomyopathy and heart failure showed sarcomeric and cytoskeletal disarrangement. On the basis of these findings we tested the hypothesis that in cardiomyopathic failing hearts not only the sarcomere structure but also the organization and the amo...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1994.1148
更新日期:1994-10-01 00:00:00
abstract::The 23Na NMR shift-reagent complexes (Dy(PPP)2, Dy(TTHA), and Tm(DOTP)) bind stoichiometric amounts of Ca2+. Thus, in perfused rat heart systems, a supplementation of Ca2+ is required to maintain the requisite extracellular free calcium concentration ([Ca(o)]f) and to approximate a physiological level of contractile f...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.2001.1459
更新日期:2001-11-01 00:00:00
abstract::The aim of this study was to investigate the effects of aging on the profile of myocardial substrate utilization and cardiac function using a physiological profile of substrates. Hearts from 6-, 15- and 24-month male Wistar rats were perfused in the isovolumic Langendorff mode, with physiological concentrations of 13C...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2005.09.018
更新日期:2006-01-01 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::Energy metabolism of quiescent cardiac muscle was studied in the isolated rabbit heart preparation perfused at constant pressure by the Langendorff technique. Oxygen consumption (MVo2), coronary flow rate (CFR) and the steady state concentrations of high energy phosphate compounds were determined in hearts rendered as...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/0022-2828(89)90863-8
更新日期:1989-02-01 00:00:00
abstract::Myocardial [ATP] falls in the failing heart. One potential compensatory mechanism for maintaining a near normal free energy of ATP hydrolysis (DeltaG approximately (ATP)), despite a fall in [ATP], may be the reduction of myocardial creatine (Cr). To test this, we conducted a longitudinal study using transgenic mice ov...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2009.10.029
更新日期:2010-04-01 00:00:00
abstract::Cell-based therapy after myocardial infarction (MI) is a promising therapeutic option but the relevant cell subsets and dosage requirements are poorly defined. We hypothesized that cell therapy for myocardial infarction is improved by ex vivo expansion and high-dose transplantation of defined hematopoietic progenitor ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2008.06.010
更新日期:2008-09-01 00:00:00
abstract::Pulmonary arterial hypertension (PAH) is associated with refractory vasoconstriction and impaired NO-mediated vasodilatation of the pulmonary vasculature. Vascular tone is regulated by light chain (LC) phosphorylation of both nonmuscle (NM) and smooth muscle (SM) myosins, which are determined by the activities of MLC ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2013.10.009
更新日期:2013-12-01 00:00:00
abstract::The aim of the study was to test if pre-ischemic treatment with bradykinin can protect against infarction in an isolated rat heart model of regional ischemia and reperfusion, and if any such protection is dependent upon activation of protein kinase C (PKC) or mediated through the nitric oxide (NO) pathway. We also inv...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1996.0226
更新日期:1996-12-01 00:00:00
abstract::Caloric restriction extends longevity and reduces the onset of chronic disease in many animal models. Recently, caloric restriction was shown in humans to be associated with lower blood pressure, decreased systemic inflammation, and improved cardiac diastolic parameters. However, the causation and mechanisms of calori...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2006.07.012
更新日期:2006-10-01 00:00:00
abstract::Cardiac hypertrophy is an adaptive process against increased work loads; however, hypertrophy also presents substrates for lethal ventricular arrhythmias, resulting in sudden arrhythmic deaths that account for about one third of deaths in cardiac hypertrophy. To maintain physiological cardiac function in the face of i...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章,评审
doi:10.1016/j.yjmcc.2006.07.021
更新日期:2006-11-01 00:00:00
abstract::Viscosity is proposed to modulate diastolic function, but only limited understanding of the source(s) of viscosity exists. In vitro experiments have shown that the proline-glutamic acid-valine-lysine (PEVK) rich element of titin interacts with actin, causing a viscous force in the sarcomere. It is unknown whether this...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2011.06.006
更新日期:2011-09-01 00:00:00