Abstract：
:Tetrahydrobiopterin (BH(4)) is an essential cofactor for aromatic amino acid hydroxylases and for all three nitric oxide synthase (NOS) isoforms. It also has a protective role in the cell as an antioxidant and scavenger of reactive nitrogen and oxygen species. Experimental studies in humans and animals demonstrate that decreased BH(4)-bioavailability, with subsequent uncoupling of endothelial NOS (eNOS) plays an important role in the pathogenesis of endothelial dysfunction, hypertension, ischemia-reperfusion injury, and pathologic cardiac remodeling. Synthetic BH(4) is clinically approved for the treatment of phenylketonuria, and experimental studies support its capacity for ameliorating cardiovascular pathophysiologies. To date, however, the translation of these studies to human patients remains limited, and early results have been mixed. In this review, we discuss the pathophysiologic role of decreased BH(4) bioavailability, molecular mechanisms regulating its metabolism, and its potential therapeutic use as well as pitfalls as an NOS-modulating drug. This article is part of a special issue entitled ''Key Signaling Molecules in Hypertrophy and Heart Failure.''
journal_name
J Mol Cell Cardioljournal_title
Journal of molecular and cellular cardiologyauthors
Moens AL,Kietadisorn R,Lin JY,Kass Ddoi
10.1016/j.yjmcc.2011.03.009subject
Has Abstractpub_date
2011-10-01 00:00:00pages
559-63issue
4eissn
0022-2828issn
1095-8584pii
S0022-2828(11)00121-0journal_volume
51pub_type
杂志文章,评审abstract：:The ultrastructure of myocardial tissue was studied during ischemia and reperfusion and during reperfusion with a calcium-containing solution after a short period of calcium-free perfusion (calcium paradox). After ischemia an aggregation of the sarcolemmal intramembranous particles was observed. Subsequent reperfusion...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/0022-2828(88)90335-5
更新日期：1988-03-01 00:00:00
abstract：:Fluorescein isothiocyanate-conjugated lectins (FTC-lectins) have been used to study the occurrence and the distribution of their receptors in the coating of mouse myocardial cells throughout their differentiation (from 10 days post-coitum to the adult stage). FTC-Con A, -WGA and -PNA specifically inhibited by alpha-ma...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/0022-2828(83)90285-7
更新日期：1983-02-01 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：:We measured mitochondrial NADH autofluorescence or Ca(2+) using Rhod-2, simultaneously with cell shortening in isolated guinea-pig ventricular myocytes. When both frequency and amplitude of twitch shortening (work intensity) were increased by raising stimulus frequency in incremental steps from 0.1 to 3.3 Hz, the stea...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2005.12.012
更新日期：2006-03-01 00:00:00
abstract：:The Raf/MAPK/ERK kinase (Mek)/extracellular signal-regulated kinases (Erk) pathway is activated in cardiac hypertrophy after a myocardial infarction. Although heat-shock protein 90 (Hsp90) may regulate the Raf/Mek/Erk signal pathway, the role of Hsp90 in pathophysiological cardiac hypertrophy remains unclear. In this ...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2018.12.010
更新日期：2019-02-01 00:00:00
abstract：:Quin2 is a fluorescent Ca2+-sensitive indicator which in its acetoxymethyl ester form can be loaded into the cytosolic compartment of cells without any disruption of the plasma membrane. Quin2 has been used with many cell types to measure changes of [Ca2+]i in response to hormones and other stimuli. In this report we ...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/s0022-2828(86)80919-1
更新日期：1986-05-01 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：:The incidence of mortality from cardiovascular diseases in higher in diabetic patients. The cause of this accelerated cardiovascular disease is multifactorial and, although atherosclerotic cardiovascular disease in association with well-defined risk factors has an influence on morbidity and mortality in diabetics, myo...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章,评审
doi：10.1016/s0022-2828(08)80016-8
更新日期：1995-01-01 00:00:00
abstract：:Heart failure of diverse causes is associated with abnormalities of sarcoplasmic reticulum (SR) Ca(2+)transport. The purpose of this study was to determine whether the thyroid hormone analogue, 3,5-diiodothyropropionic acid (DITPA), prevents abnormal Ca(2+)transport and expression of SR proteins associated with post-i...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1006/jmcc.2000.1225
更新日期：2000-11-01 00:00:00
abstract：:Heart failure is associated with mitochondrial dysfunction so that restoring or improving mitochondrial health is of therapeutic importance. Recently, reduction in NAD+ levels and NAD+-mediated deacetylase activity has been recognized as negative regulators of mitochondrial function. Using a cardiac specific KLF4 defi...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2017.09.001
更新日期：2017-11-01 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 length-dependence of myofilament Ca(2+) sensitivity is considered to be an important component of the steep force-length relationship in cardiac muscle (Frank-Starling relation). Recent studies suggest that Ca(2+) sensitivity is a function of the number of strong-binding cross-bridge interactions formed at a given...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1006/jmcc.1999.1043
更新日期：1999-12-01 00:00:00
abstract：:In general, in most organ systems, intracellular protein homeostasis is the sum of many factors, including chromosomal state, protein synthesis, post-translational processing and transport, folding, assembly and disassembly into macromolecular complexes, protein stability and clearance. In the heart, there has been a ...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章,评审
doi：10.1016/j.yjmcc.2013.12.015
更新日期：2014-06-01 00:00:00
abstract：:In recently published studies, we show that angiotensin II (AII) generated from an engineered rat angiotensinogen cDNA, and maintained intracellularly, is growth stimulatory for a rat hepatoma cell line. In the present study, we report that co-expression of AII fused to cyan fluorescent protein (ECFP/AII) and angioten...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2003.09.021
更新日期：2004-01-01 00:00:00
abstract：:Fibrosis, which is defined as excessive accumulation of fibrous connective tissue, contributes to the pathogenesis of numerous diseases involving diverse organ systems. Cardiac fibrosis predisposes individuals to myocardial ischemia, arrhythmias and sudden death, and is commonly associated with diastolic dysfunction. ...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2013.12.013
更新日期：2014-02-01 00:00:00
abstract：:We have investigated whether translocation of constitutive low molecular weight stress proteins (alphaB-crystallin and HSP27) to the myofilament/cytoskeletal compartment occurs during ischemic preconditioning and assessed if this is causally associated with cardioprotection. Triton-insoluble preparations from fresh or...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1006/jmcc.2000.1136
更新日期：2000-06-01 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：:The aims of our study were to determine mortality, and age- and genotype-related cardiac phenotype in endothelial nitric oxide synthase (NOS) knockout (-/-) and wild-type (+/+) mice. Male and female (-/-) and male and female (+/+) conscious mice were studied at different ages by echocardiography and tail-cuff blood pr...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2004.05.005
更新日期：2004-09-01 00:00:00
abstract：:Therapeutic angiogenesis can be induced by the implantation of bone marrow cells (BMCs). However, the mechanism of BMC-mediated neovascularization remains to be clarified. We investigated the differential activities of bone marrow subpopulations in angiogenesis and cytokine production. BMCs were separated into positiv...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2007.08.001
更新日期：2007-11-01 00:00:00
abstract：:The ability of human pluripotent stem cells (hPSCs) to differentiate into any cell type of the three germ layers makes them a very promising cell source for multiple purposes, including regenerative medicine, drug discovery, and as a model to study disease mechanisms and progression. One of the first specialized cell ...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章,评审
doi：10.1016/j.yjmcc.2013.12.011
更新日期：2014-02-01 00:00:00
abstract：:Oxidative stress can be generated at several sites within the mitochondria. Among these, monoamine oxidase (MAO) has been described as a prominent source. MAOs are mitochondrial flavoenzymes responsible for the oxidative deamination of catecholamines, serotonin and biogenic amines, and during this process they generat...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章,评审
doi：10.1016/j.yjmcc.2013.12.032
更新日期：2014-08-01 00:00:00
abstract：:Multiple studies have shown that phospholamban (PLN) plays a key role in regulation of frequency-dependent increase of cardiac contraction, a hallmark of the contractile reserve in myocardium. However, the mechanisms underlying this relationship remain elusive. Phosphorylation of PLN occurs on residues: serine-16 (Ser...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2004.05.013
更新日期：2004-08-01 00:00:00
abstract：:Endothelial cells produce endothelin, a powerful vasoconstrictor. We report the release of additional vasoconstrictor material in conditional filtrate from freshly harvested cells, which we identified as leukotrienes by radioimmunoassay (RIA) and by high pressure liquid chromatography (HPLC). The material was collecte...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1006/jmcc.1993.1077
更新日期：1993-06-01 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：:The purpose of the present study was to determine whether age-related changes in the expression and function of the cardiac isoform of the sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2a) play a role in SR Ca(2+)release and cell contraction. SERCA2a protein levels and subcellular localization were compared between fetal...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1006/jmcc.2000.1116
更新日期：2000-05-01 00:00:00
abstract：:Cardioprotection and preconditioning mediated via G-protein-coupled receptors may be lost or impaired with advancing age, limiting ischemic tolerance and the ability to pharmacologically protect older hearts from ischemic injury. Our preliminary findings indicated a loss of delta-opioid receptor-mediated protection in...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2007.02.011
更新日期：2007-05-01 00:00:00
abstract：:Angiotensin (Ang) II plays an important role in post-myocardial infarction (MI) cardiac remodeling. The Ang II type 1 (AT(1)) receptor which mediates most Ang II effects is upregulated on non-myocytes in the post-MI heart. We have shown that pro-inflammatory cytokines increase AT(1) receptor density on cardiac fibrobl...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2004.12.015
更新日期：2005-03-01 00:00:00
abstract：:Milrinone, a potent positive inotropic and vasodilating agent, has shown promise in the clinical treatment of congestive heart failure, but significant controversy about its mechanism of action exists. To approach these mechanistic problems in a non-innervated, non-diffusion-limited system, the effects of milrinone on...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/s0022-2828(87)80548-5
更新日期：1987-01-01 00:00:00
abstract：:We examined the relative roles of the mitogen-activated protein kinases (MAPK) in mediating the alpha1-adrenergic receptor (alpha1-AR) stimulated hypertrophic phenotype in adult rat ventricular myocytes (ARVM). Norepinephrine (NE; 1 microM) in the presence of the beta -AR antagonist propranolol (Pro; 2 microM) caused ...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1006/jmcc.2001.1348
更新日期：2001-04-01 00:00:00
abstract：:Pacemaker (HCN) channels have a key role in the generation and modulation of spontaneous activity of sinoatrial node myocytes. Previous work has shown that compartmentation of HCN4 pacemaker channels within caveolae regulates important functions, but the molecular mechanism responsible is still unknown. HCN channels h...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2012.05.013
更新日期：2012-08-01 00:00:00
