Abstract:
:In this study, we looked into possible compensatory changes of other adenosine receptors (ARs) in A(2A) genetic knockout mice (A2AKO) as well as the functional role of nitric oxide (NO) in A(2A) AR-mediated vasodilation. Gene expression of ARs from coronary arteries of A(2A) AR wild type mice (A2AWT) and A2AKO was studied using real-time PCR. Functional studies were carried out in isolated heart and isolated coronary artery preparations. A(2B) AR was found to be 4.5 fold higher in A2AKO than in A2AWT, while A(2A) AR expression was absent in A2AKO. There was no difference in A(1) and A(3) ARs between WT and KO animals. The concentration-relaxation curve for adenosine-5'-N-ethylcarboxamide (NECA, non-selective AR agonist) in isolated coronary arterial rings in A2AKO was shifted to the left when compared to A2AWT. The concentration-response curve for A(2B) selective agonist (BAY 60-6583) was also shifted to the left in A2AKO hearts. L-NAME, a non-specific NO synthase inhibitor, did not affect baseline coronary flow (CF) until the concentration reached 10 microM in A2AWT (76.32+/-11.35% from baseline, n=5). In A2AKO, the CF decreased significantly by L-NAME only at a higher concentration (100 microM, 93.32+/-5.8% from baseline, n=5). L-NMA (1 microM, n=4), another non-specific NO synthase inhibitor, also demonstrated similar results in decreasing CF (59.66+/-3.23% from baseline in A2AWT, while 81.76+/-8.91% in A2AKO). It was further demonstrated that the increase in CF by 100 microM NECA was significantly blunted with 10 microM L-NAME (377.08+/-25.23% to 305.41+/-30.73%, n=9) in A2AWT but not in A2AKO (153.66+/-22.7% to 143.88+/-36.65%, n=5). Similar results were also found using 50 nM of CGS-21680 instead of NECA in A2AWT (346+/-22.85 to 277+/-31.39, n=6). No change in CF to CGS-21680 was noted in A(2A)AKO. Our data demonstrate, for the first time, that coronary A(2B) AR was up-regulated in mice deficient in A(2A) AR. We also provide direct evidence supporting a role for NO in A(2A) AR-mediated coronary vasodilation. The data further support the role for A(2A) AR in the regulation of basal coronary tone through the release of NO.
journal_name
J Mol Cell Cardioljournal_title
Journal of molecular and cellular cardiologyauthors
Teng B,Ledent C,Mustafa SJdoi
10.1016/j.yjmcc.2008.03.003subject
Has Abstractpub_date
2008-05-01 00:00:00pages
905-14issue
5eissn
0022-2828issn
1095-8584pii
S0022-2828(08)00348-9journal_volume
44pub_type
杂志文章abstract::Cardiac disease is frequently associated with abnormalities in electrical function that can severely impair cardiac performance with potentially fatal consequences. The available therapeutic options have some efficacy but are far from perfect. The curative potential of gene therapy makes it an attractive approach for ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章,评审
doi:10.1016/j.yjmcc.2010.07.022
更新日期:2011-05-01 00:00:00
abstract::Aquaporins (AQPs) are a family of water channel proteins that assist in maintenance of the cellular osmotic environment and whole body fluid balance. Specialized organ-specific AQPs are important in physiologic and pathologic processes but little is known about AQPs in the human heart. AQP1 has been identified in rode...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2004.01.009
更新日期:2004-05-01 00:00:00
abstract::Thoracic aortic aneurysm/dissection (TAAD) is characterized by excessive smooth muscle cell (SMC) loss, extracellular matrix (ECM) degradation and inflammation. However, the mechanism whereby signaling leads to SMC loss is unclear. We used senescence-associated (SA)-β-gal staining and analysis of expression of senesce...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2016.08.008
更新日期:2016-10-01 00:00:00
abstract::(±)-Sodium5-bromo-2-(α-hydroxypentyl) benzoate (brand name: brozopine, BZP, 1a), derived from L-3-n-butylphthalide (L-NBP), has been reported to protect the brain from stoke and has been approved by CFDA in Phase I-II clinical trials. However, it remains to be investigated whether 1a may exhibit any cardioprotective e...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2019.07.014
更新日期:2019-10-01 00:00:00
abstract::The right ventricle (RV) differs in several aspects from the left ventricle (LV) including its embryonic origin, physiological role and anatomical design. In contrast to LV hypertrophy, little is known about the molecular circuits, which are activated upon RV hypertrophy (RVH). We established a highly reproducible mod...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2010.07.014
更新日期:2010-10-01 00:00:00
abstract::Pathologic cardiac hypertrophy can lead to heart failure, but the mechanisms involved are poorly understood. SERCA2 is critical for normal cardiac calcium handling and function and SERCA2 mRNA and protein levels are reduced by cardiac hypertrophy. We hypothesized that extracellular signal-regulated kinase (ERK) 1/2 ac...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2014.06.018
更新日期:2014-10-01 00:00:00
abstract::We have tested the hypothesis that thyroid state may influence both the flow of cellular Ca2+ and the myofilament response to Ca2+ by effects on intracellular pH (pHi) and Na+ (Nai+). Single cardiac myocytes isolated from hypothyroid, euthyroid and hyperthyroid animals were loaded with fura-2/AM (Cai2+ probe), BCECF/A...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1997.0495
更新日期:1997-10-01 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::The effects of the inhibition of phospholipid degradation and superoxide radical generation on prostaglandin synthesis associated with myocardial ischemia and reperfusion were studied in the isolated, in-situ pig heart model subjected to 60 mins of regional ischemia and a further 60 mins of hypothermic potassium cardi...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/s0022-2828(86)80009-8
更新日期:1986-09-01 00:00:00
abstract::Vascular cells are very sensitive to their hemodynamic environment. Any change in blood pressure or blood flow can be sensed by endothelial and vascular smooth muscle cells and ultimately results in structural modifications within the vascular wall that accommodate the new conditions. In the case of hypertension, the ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章,评审
doi:10.1016/j.yjmcc.2009.09.018
更新日期:2010-03-01 00:00:00
abstract::Global ischemia in guinea-pig hearts for 60 to 90 min depressed microsomal and mitochondrial Ca2+ uptake activities. Reperfusion of the 60 min ischemic hearts resulted in incomplete recovery of contractile function and calcium uptake activities of both mitochondrial and microsomal fractions. On the other hand, reperfu...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/0022-2828(88)90327-6
更新日期:1988-03-01 00:00:00
abstract::To investigate the interaction of cytoskeleton with the receptor modulation of ionic currents, we studied the effect of muscarinic and beta-adrenergic stimulation in adult guinea-pig ventricular cardiac myocytes treated with paclitaxel and colchicine, two drugs that respectively stabilize or destabilize microtubules. ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/s0022-2828(02)00312-7
更新日期:2003-02-01 00:00:00
abstract::The present study was undertaken to assess whether [32P]uptake and autoradiography could be used as an indicator of regional myocardial oxygen consumption. Rat hearts were perfused in the Langendorff mode with medium containing [32P]orthophosphate (32Pi) and the incorporation of label into ATP, perchloric acid-insolub...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1993.1035
更新日期:1993-03-01 00:00:00
abstract::Studies using chemically-induced models of diabetes have shown the diabetic myocardium to exhibit abnormalities in cellular ion transport, which may affect susceptibility to reperfusion-induced arrhythmias. We studied the incidence of reperfusion-induced ventricular tachycardia (VT) and fibrillation (VF) in isolated h...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/0022-2828(92)93195-p
更新日期:1992-04-01 00:00:00
abstract::Chronic kidney disease (CKD) is a significant risk factor for cardiovascular and peripheral vascular disease. Although mesenchymal stem cell (MSC)-based therapy is a promising strategy for treatment of ischemic diseases associated with CKD, the associated pathophysiological conditions lead to low survival and prolifer...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2016.05.011
更新日期:2016-08-01 00:00:00
abstract::CD34+ progenitor cells hold promise for therapeutic neovascularization in various settings. In this study, the role of human peripheral blood CD34+ cells in neovascularization and inflammatory cell recruitment was longitudinally studied in vivo. Human CD34+ cells were incorporated in Matrigel, implanted subcutaneously...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2007.03.907
更新日期:2007-06-01 00:00:00
abstract::The kinetics of Ca influx by Na/Ca exchange into adult rat heart cells loaded with Na and depleted of ATP were investigated, to further elucidate how ATP regulates exchanger properties in the intact heart cell. We found an eight-fold reduction in Vmax for Ca uptake by ATP depletion, with no significant change in the K...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1996.0294
更新日期:1997-02-01 00:00:00
abstract::The myosin heavy chain (MHC) isoforms, alpha- and beta-MHC, are expressed in developmental- and chamber-specific patterns. Healthy human ventricle contains approximately 2-10% alpha-MHC and these levels are reduced even further in the failing ventricle. While down-regulation of alpha-MHC in failing myocardium is consi...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2009.10.013
更新日期:2010-05-01 00:00:00
abstract::One of the major issues in myocardial gene therapy is poor transfection efficiency. The herpes simplex virus protein VP22 is known to facilitate intercellular protein transport. Not only VP22 but also VP22-linked protein are exported from the cytoplasm of cells, in which it is synthesised endogenously, and transferred...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2004.01.007
更新日期:2004-04-01 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::Heat shock protein 27 (Hsp27) and alpha B-crystallin (alphaBC) are small heat shock proteins that stabilize the myofilament during stress. We utilized two-dimensional gel electrophoresis (2-DE), phospho-fluorescence staining, titanium dioxide (TiO(2)) phosphopeptide purification and mass spectrometry (MS) to fully cha...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2006.02.007
更新日期:2006-06-01 00:00:00
abstract::Heart failure patients have abnormal cardiac high energy phosphate metabolism, the explanation for which is unknown. Patients with heart failure also have elevated plasma free fatty acid (FFA) concentrations. Elevated FFA levels are associated with increased cardiac mitochondrial uncoupling proteins (UCPs), which, in ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2008.01.008
更新日期:2008-04-01 00:00:00
abstract::Mild or low doses of oxidants are known to prime cells towards resistance against further damage. In cardiomyocytes, we found that pretreatment with 100 microM H(2)O(2) prevents the cells from apoptosis induced by doxorubicin (Dox). Affymetrix microarray analyses of 28,000 genes reveal that H(2)O(2) treated cells redu...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2006.09.012
更新日期:2007-01-01 00:00:00
abstract::This study was designed to examine whether diltiazem, a calcium channel-blocker, inhibits the cardiac ultrastructural alterations induced by coronary occlusion with or without reperfusion, in dogs anesthetized with pentobarbital. The left anterior descending coronary artery (LAD) was completely occluded for 60 min wit...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/s0022-2828(86)80903-8
更新日期:1986-04-01 00:00:00
abstract::The Gq-RhoA-Rho kinase pathway, activated by neurohormonal factors such as angiotensin II (Ang II), has been proposed to be one of the important signaling pathways involved in the progression of left ventricular (LV) hypertrophy to heart failure. We tested the hypothesis that chronic inhibition of Rho kinase prevents ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/s0022-2828(02)00278-x
更新日期:2003-01-01 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::The sodium/potassium ATPase (NKA) is essential for establishing the normal intracellular [Na+] and [K+] and transmembrane gradients that are essential for many cellular functions, including cardiac electrophysiology and contractility. Different NKA isoforms exhibit differential expression levels, cellular localization...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2017.05.013
更新日期:2017-07-01 00:00:00
abstract::Pulmonary arterial hypertension (PAH) is a complex disease that causes significant morbidity and mortality and is clinically characterized by an increase in pulmonary vascular resistance. The histopathology is marked by vascular proliferation/fibrosis, remodeling, and vessel obstruction. Development of PAH involves th...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章,评审
doi:10.1016/j.yjmcc.2007.09.006
更新日期:2008-01-01 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::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