Abstract:
:Diabetes mellitus is associated with an increased incidence and greater severity of primary atherosclerosis as well as restenosis after angioplasty for reasons not yet clear. We have shown previously that insulin and proinsulin-typically elevated in blood in patients with type II diabetes-increase plasma activity of plasminogen activator inhibitor type 1 (PAI-1)in vivo. Others have demonstrated that increased PAI-1 activity is associated with coronary heart disease. Accordingly, the present study was performed to identify sites of increased expression of the PAI-1 gene within the vessel wall. Equimolar concentrations of insulin, proinsulin, or vehicle alone as a control, were administered intravenously over 1 h to conscious rabbits that were kept euglycemic throughout by the use of glucose clamping. Within 3 h plasma PAI-1 activity increased from 1.15+/-1.34 to 11.33+/-4.30 AU/ml with insulin (mean+/-s.d., P=0.015) and from 2.83+/-0.74 to 15.43+/-4.70 AU/ml with proinsulin (P=0.035). This was found to be in contrast to the controls where the increase in plasma PAI-1 activity was of lesser degree (2.43+/-1.86 to 6.80+/-1.10 AU/ml, P=n.s., n=4 each). As judged from the results of in situ hybridization, the site of prominent aortic expression of the PAI-1 gene was the endothelium. Furthermore, expression increased further in this site after administration of insulin or proinsulin. As judged from results of immunohistochemistry, PAI-1 protein in the aorta was also prominent in endothelium. These results suggest that "hyper(pro)insulinemia", increases PAI-1 not only in blood but also in arterial endothelium. Thus, attenuation of vasculopathy and especially of restenosis after angioplasty in type II diabetes may be possible with somatic gene therapy targeting PAI-1 expression in endothelial cells.
journal_name
J Mol Cell Cardioljournal_title
Journal of molecular and cellular cardiologyauthors
Nordt TK,Sawa H,Fujii S,Bode C,Sobel BEdoi
10.1006/jmcc.1998.0719subject
Has Abstractpub_date
1998-08-01 00:00:00pages
1535-43issue
8eissn
0022-2828issn
1095-8584pii
S0022-2828(98)90719-2journal_volume
30pub_type
杂志文章abstract::Cardiac fibroblasts represent one of the most frequent cell type in the heart of rodents and humans and alterations of their phenotype have a great impact on cardiac function. Due to aging, ischemic injuries, valvular dysfunctions, hypertension and aortic stenosis, multiple signals trigger the accumulation of extracel...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章,评审
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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...
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更新日期:2016-09-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
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更新日期:2011-01-01 00:00:00
abstract::Readmission of Ca2+ after a short period of Ca2+-free perfusion results in a rapid and massive release of cytoplasmic proteins from the heart (calcium paradox). Maximal release rates of proteins are already reached within 2 min after Ca2+ repletion. The precise mechanism underlying the loss of cellular membrane integr...
journal_title:Journal of molecular and cellular cardiology
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doi:10.1016/s0022-2828(88)80119-6
更新日期:1988-07-01 00:00:00
abstract::Exposure of fine trabeculae isolated from the ferret right ventricle to media depleted of Ca2+, with a rapid perfusion system, causes a depolarization of the membrane and a rise in aiNa. This rise in aiNa is sigmoidally dependent upon the bathing free [Ca2+], is antagonized by reduction of the [Na]o, raised [Mg]o and ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/0022-2828(90)90953-y
更新日期:1990-05-01 00:00:00
abstract::Activation of adenosine A(3) receptor (A(3)AR) protects against ischemia/reperfusion injury in the heart. However, the downstream signaling mechanisms leading to its delayed anti-ischemic effects remain unclear. We hypothesized that A(3)AR stimulation protects the heart via activation of nuclear transcription factor k...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.2001.1510
更新日期:2002-03-01 00:00:00
abstract::During pressure overload hypertrophy, selective changes in cardiac gene expression occur that regulate growth and modify the structural and functional properties of the myocardium. To determine the role of translational mechanisms, a murine model of transverse aortic constriction was used to screen a set of specified ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
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更新日期:2008-01-01 00:00:00
abstract::Heterotrimeric G-proteins, composed of Galpha and Gbetagamma subunits, transmit numerous and diverse extracellular stimuli via a large family of heptahelical cell-surface receptors to various intracellular effector molecules. The Gbetagamma subunit plays a central role in G-protein signaling. The Gbeta subunit belongs...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章,评审
doi:10.1016/j.yjmcc.2004.04.019
更新日期:2004-08-01 00:00:00
abstract::Autophagy is a process that removes damaged proteins and organelles and is of particular importance in terminally differentiated cells such as cardiomyocytes, where it has primarily a protective role. We investigated the involvement of inositol(1,4,5)trisphosphate (Ins(1,4,5)P(3)) and its receptors in autophagic respo...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2012.10.014
更新日期:2013-01-01 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::To examine cardiac myosin gene structure and expression in a non-human primate model for human heart development and disease, we have constructed a cDNA library from baboon atrium and used baboon beta-myosin heavy chain (beta-MHC)* cDNA probes to isolate atrial MHC clones. The nucleotide sequence of one such clone, la...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/0022-2828(89)90805-5
更新日期:1989-10-01 00:00:00
abstract::Diabetic cardiomyopathy is responsible for substantial morbidity and mortality in the diabetic population. Increased oxidative stress has been associated with the pathogenesis of chronic diabetic complications including cardiomyopathy. Multiple biochemical mechanisms have been proposed to increase oxidative stress in ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2003.09.007
更新日期:2003-12-01 00:00:00
abstract::The effect of isoproterenol on mechanical function was studied in the isolated arterially perfused heart of the fetal (21st and 28th day of gestation) and newborn rabbits. The inotropic effect of isoproterenol in the fetus was less than in the newborn. In contrast, myocardial cyclic AMP levels after isoproterenol infu...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/s0022-2828(87)80557-6
更新日期:1987-02-01 00:00:00
abstract::Oxidative stress markedly alters protein function through redox modification of sulfhydryl groups present in cysteine residues. To explore the role of redox state in modulating cardiac K+ channels, this study examined the effects of sulfhydryl modifiers on the repolarizing transient outward current (Ito) in voltage-cl...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.2002.2112
更新日期:2002-12-01 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::Aftercontractions induced by beta-adrenoceptor stimulation in human and guinea-pig cardiomyocytes may be related to changes in action potential duration (APD). We investigated the effects of altering APD during the occurrence of isoproterenol-induced aftercontractions, using the KATP channel openers cromakalim and lem...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1997.0385
更新日期:1997-05-01 00:00:00
abstract::The role of protein kinase C (PKC) in the protection of ischemic preconditioning (PC) is still controversial, partly because of the multiple isozymes of PKC and the inability to directly measure PKC activity in vivo. In this study we have used novel peptide inhibitors which correspond to part of the amino acid sequenc...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1999.1026
更新日期:1999-10-01 00:00:00
abstract::Brain renin-angiotensin system (RAS) hyperactivity has been implicated in sympathetic hyperactivity and progressive left ventricular (LV) dysfunction after myocardial infarction (MI). Angiotensin III, generated by aminopeptidase A (APA), is one of the main effector peptides of the brain RAS in the control of cardiac f...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2018.12.008
更新日期:2019-02-01 00:00:00
abstract::Phosphorylation of myosin binding protein C (MyBP-C) was investigated in intraventricular septum samples taken from patients with hypertrophic cardiomyopathy undergoing surgical septal myectomy. These samples were compared with donor heart muscle, as a well-characterised control tissue, and with end-stage failing hear...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2008.05.020
更新日期:2008-08-01 00:00:00
abstract::Adequate wound healing and scar formation is an essential response to myocardial infarction (MI), and fibroblasts are primary cellular components regulating the process. How fibroblast functions are altered post-MI and to what extent these abnormalities persist in vitro is not well understood. Accordingly, we isolated...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2005.07.008
更新日期:2005-10-01 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
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2012.01.007
更新日期:2012-05-01 00:00:00
abstract::Phospholamban (PLN) is a key regulator of cardiac contraction and relaxation through its inhibition of the sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA2a). The inhibitory effect is attenuated upon protein kinase A (PKA) dependent phosphorylation of PLN. PLN exists in an equilibrium of pentamers and monomers. While...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2014.12.020
更新日期:2015-03-01 00:00:00
abstract::Thyroid hormone has unique properties affecting the heart, and the vasculature and cholesterol metabolism. There is interest in using thyromimetic agents as possible treatment options for heart failure based on data demonstrating the ability of these agents to improve systolic and diastolic left ventricular function a...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章,评审
doi:10.1016/j.yjmcc.2010.12.012
更新日期:2011-10-01 00:00:00
abstract::Genome-wide association studies (GWAS) have identified genetic variants in a number of chromosomal regions that are associated with atrial fibrillation (AF). The mechanisms underlying these associations are unknown, but are likely to involve effects of the risk haplotypes on expression of neighbouring genes. To invest...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2015.06.005
更新日期:2015-08-01 00:00:00
abstract:INTRODUCTION:Fibroblast activation protein α (FAP) is a membrane-bound serine protease expressed by activated fibroblasts during wound healing in the skin. Expression of FAP after myocardial infarction (MI) and potential effects on cardiac wound healing are largely unknown. METHODS:MI was induced in rats and FAP expre...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2015.08.016
更新日期:2015-10-01 00:00:00
abstract::Acute adriamycin cardiotoxicity was studied in the isolated, perfused rat heart by 31P and 13C NMR spectroscopy at flow rates of 15 and 5 ml/min. Treated hearts received a total dose of 13.5 mg of adriamycin. 31P NMR spectra were collected at the beginning and end of each experiment, and cardiac function was recorded ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/0022-2828(90)90082-d
更新日期:1990-10-01 00:00:00
abstract::Ventricular trabeculae from adult and newborn ferret heart were chemically skinned by Triton X-100 which disrupts all cellular membranes. In newborn preparations, maximal Ca(2+)-activated tension was two times smaller than in adult fibres while Ca2+ sensitivity was higher. Caffeine (10 mM) and cyclopiazonic acid (100 ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1996.0119
更新日期:1996-06-01 00:00:00
abstract::The sulfur-containing beta-amino acid, taurine, is the most abundant free amino acid in cardiac and skeletal muscle. Although its physiological function has not been established, it is thought to play an important role in ion movement, calcium handling, osmoregulation and cytoprotection. To begin examining the physiol...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2008.03.001
更新日期:2008-05-01 00:00:00
abstract::Various drugs are reported to prolong the QT-interval on the surface ECG, thereby increasing the risk of developing a potentially fatal arrhythmia known as Torsades de Pointes (TdP). TdP case reports for these drugs have often been associated with risk factors such as overdosing, concomitant drugs and/or existing path...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2004.09.001
更新日期:2004-11-01 00:00:00