Abstract:
:Inducible nitric oxide synthase (iNOS) protein is expressed in cardiac myocytes of patients and experimental animals with congestive heart failure (CHF). Here we show that iNOS expression plays a role in pressure overload-induced myocardial chamber dilation and hypertrophy. In wild-type mice, chronic transverse aortic constriction (TAC) resulted in myocardial iNOS expression, cardiac hypertrophy, ventricular dilation and dysfunction, and fibrosis, whereas iNOS-deficient mice displayed much less hypertrophy, dilation, fibrosis, and dysfunction. Consistent with these findings, TAC resulted in marked increases of myocardial atrial natriuretic peptide 4-hydroxy-2-nonenal (a marker of lipid peroxidation) and nitrotyrosine (a marker for peroxynitrite) in wild-type mice but not in iNOS-deficient mice. In response to TAC, myocardial endothelial NO synthase and iNOS was expressed as both monomer and dimer in wild-type mice, and this was associated with increased reactive oxygen species production, suggesting that iNOS monomer was a source for the increased oxidative stress. Moreover, systolic overload-induced Akt, mammalian target of rapamycin, and ribosomal protein S6 activation was significantly attenuated in iNOS-deficient mice. Furthermore, selective iNOS inhibition with 1400W (6 mg/kg per hour) significantly attenuated TAC induced myocardial hypertrophy and pulmonary congestion. These data implicate iNOS in the maladaptative response to systolic overload and suggest that selective iNOS inhibition or attenuation of iNOS monomer content might be effective for treatment of systolic overload-induced cardiac dysfunction.
journal_name
Circ Resjournal_title
Circulation researchauthors
Zhang P,Xu X,Hu X,van Deel ED,Zhu G,Chen Ydoi
10.1161/01.RES.0000264081.78659.45subject
Has Abstractpub_date
2007-04-13 00:00:00pages
1089-98issue
7eissn
0009-7330issn
1524-4571pii
01.RES.0000264081.78659.45journal_volume
100pub_type
杂志文章abstract::The purpose of these studies was to evaluate cardiovascular structural and functional changes in a model of hypertension-induced myocardial hypertrophy in which vasodilator therapy decreased blood pressure to normal levels. Thus, we determined the separate contributions of hypertension and hypertrophy on myocardial an...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.64.6.1127
更新日期:1989-06-01 00:00:00
abstract::To investigate the relation of pressure and vascular wall thickening in hypertension, we coarcted the abdominal aorta upstream to the renal arteries in 14 rats. Sham-coarcted (n = 16) and two-kidney, one-clip (Goldblatt) hypertensive rats (n = 13) served as controls. Tail, femoral, and carotid arterial pressures rose ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.62.5.1001
更新日期:1988-05-01 00:00:00
abstract::The prevalence of obesity has increased worldwide over the past few decades. In 2013, the prevalence of obesity exceeded the 50% of the adult population in some countries from Oceania, North Africa, and Middle East. Lower but still alarmingly high prevalence was observed in North America (≈30%) and in Western Europe (...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.115.306883
更新日期:2016-05-27 00:00:00
abstract::RNA splicing represents a post-transcriptional mechanism to generate multiple functional RNAs or proteins from a single transcript. The evolution of RNA splicing is a prime example of the Darwinian function follows form concept. A mutation that leads to a new mRNA (form) that encodes for a new functional protein (func...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.115.307872
更新日期:2016-02-05 00:00:00
abstract::The remodeling of ventricular gap junctions, as defined by changes in size, distribution, or function, is a prominent feature of diseased myocardium. However, the regulation of assembly and maintenance of gap junctions remains poorly understood. To investigate N-cadherin function in the adult myocardium, we used a flo...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000181132.11393.18
更新日期:2005-09-02 00:00:00
abstract::Inherited mutations and a polymorphism in minK-related peptide 1 (MiRP1) have been linked to congenital or acquired long-QT syndrome, pointing to the importance of MiRP1 in maintaining the cardiac electrical stability. We tested whether MiRP1 could affect the function of Kv4.x (x=2 and 3), the major pore-forming (alph...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/hh1001.090839
更新日期:2001-05-25 00:00:00
abstract::Fluid shear stress caused by blood flow is a major determinant of vascular remodeling and arterial tone and can lead to development of atherosclerosis. The endothelial monolayer in vivo acts as a signal transduction interface for hemodynamic forces; these forces determine the shape, cytoskeletal organization, and func...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/01.RES.0000200162.94463.d7
更新日期:2006-02-03 00:00:00
abstract::This review reflects and expands on the contents of my presentation at the Thomas W. Smith Memorial Lecture at American Heart Association Scientific Sessions, 2011. "Decoding the cardiac message" refers to accumulating results from ongoing microRNA research that is altering longstanding concepts of the mechanisms for,...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.111.256768
更新日期:2012-03-02 00:00:00
abstract::Recent studies have suggested a proangiogenic effect of angiotensin-converting enzyme (ACE) inhibition. We hypothesized that such a proangiogenic effect of ACE inhibition may be mediated, in part, by bradykinin (BK) B(2)-receptor pathway. This study therefore examined the neovascularization induced by ACE inhibitor tr...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/hh2001.097691
更新日期:2001-10-12 00:00:00
abstract:RATIONALE:Innate and adaptive immune responses alter numerous homeostatic processes that are controlled by nuclear hormone receptors. NR4A1 is a nuclear receptor that is induced in vascular pathologies, where it mediates protection. OBJECTIVE:The underlying mechanisms that regulate the activity of NR4A1 during vascula...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.111.258814
更新日期:2012-04-13 00:00:00
abstract::We recently established a new transgenic mouse model with brain-restricted overexpression of angiotensin II (Ang II) type 1a receptors (NSE-AT(1a)) to unmask the role of the brain renin-angiotensin system in hypertension. To test the hypothesis that these mice would exhibit an early exacerbation of renovascular hypert...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000140892.86313.c2
更新日期:2004-09-03 00:00:00
abstract:RATIONALE:The sarcolemma of cardiomyocytes contains many proteins that are essential for electromechanical function in general, and excitation-contraction coupling in particular. The distribution of these proteins is nonuniform between the bulk sarcolemmal surface and membrane invaginations known as transverse tubules ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.120.317266
更新日期:2021-01-22 00:00:00
abstract:RATIONALE:Cryptogenic strokes, those of unknown cause, have been estimated as high as 30% to 40% of strokes. Inflammation has been suggested as a critical etiologic factor. However, there is lack of experimental evidence. OBJECTIVE:In this study, we investigated inflammation-associated stroke using a mouse model that ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.116.310349
更新日期:2017-12-08 00:00:00
abstract::Pulsatile pulmonary hemodynamics were analyzed in a chronic awake canine high flow model. Standard mean flow and pulsatile flow hemodynamics were measured and alterations in the proximal pulmonary vascular physical properties were quantified by the characteristic impedance (Zo). Pulmonary vascular resistance (PVR), wh...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.45.2.267
更新日期:1979-08-01 00:00:00
abstract::The positive inotropic effect of the beta-adrenoceptor agonist isoproterenol is accompanied by inhibition of phosphatase type 1 activity in myocardium. Indirect assays suggest that this effect is due to activation of protein phosphatase inhibitor-1, which inhibits phosphatase activity only when phosphorylated. To test...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.69.6.1450
更新日期:1991-12-01 00:00:00
abstract::Caspase-1 processes the interleukin (IL)-1beta and IL-18 inactive precursors to the biologically active cytokines that are known to have proatherogenic effects. The present study investigated the genetic variability of the CASP1 gene and plasma levels of caspase-1 in relation to cardiovascular risk. In Europeans, 3 ta...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000232324.87983.4b
更新日期:2006-07-07 00:00:00
abstract::Although functional coupling between protein kinase Cepsilon (PKCepsilon) and mitochondria has been implicated in the genesis of cardioprotection, the signal transduction mechanisms that enable this link and the identities of the mitochondrial proteins modulated by PKCepsilon remain unknown. Based on recent evidence t...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000069215.36389.8D
更新日期:2003-05-02 00:00:00
abstract::Heptanol blocks sodium current (INa) in nerve, but its effects on cardiac INa have not been well characterized. Block of INa by heptanol was studied in 16 internally perfused voltage-clamped cardiac Purkinje cells at reduced Na+ (45 mM outside, 0 mM inside). Heptanol block of peak sodium conductance was well described...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.68.4.977
更新日期:1991-04-01 00:00:00
abstract::Shear stress caused by the frictional forces of a fluid moving over a cell monolayer is an important regulator of gene expression. In this study, we investigated the effect of shear stress on angiotensin-converting enzyme (ACE) expression and promoter activity in vitro and on local vascular ACE activity in vivo. ACE a...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.80.3.312
更新日期:1997-03-01 00:00:00
abstract::Oxidized phospholipids, including oxidation products of palmitoyl-arachidonyl-phosphatidyl choline (PAPC), are mediators of inflammation in endothelial cells (ECs) and known to induce several chemokines, including interleukin-8 (IL-8). In this study, we show that oxidized PAPC (OxPAPC), which accumulates in atheroscle...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000146030.53089.18
更新日期:2004-10-15 00:00:00
abstract::The programmed onset of myocardial dysfunction and its progression to congestive heart failure in the cardiomyopathic Syrian hamster is hallmarked by alterations in myocellular calcium regulation. To determine whether calcium channel blockade is effective in halting the progressive depression of myocardial contractile...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.67.6.1381
更新日期:1990-12-01 00:00:00
abstract::Gene therapy, aimed at the correction of key pathologies being out of reach for conventional drugs, bears the potential to alter the treatment of cardiovascular diseases radically and thereby of heart failure. Heart failure gene therapy refers to a therapeutic system of targeted drug delivery to the heart that uses fo...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.113.300269
更新日期:2013-08-30 00:00:00
abstract::We evaluated the contribution of intramural electrical events in initiation and maintenance of ventricular tachycardia in 15 dogs 3-8 days after either permanent (n = 2) or transient (n = 13) coronary artery occlusion. Seven of the dogs (47%) demonstrated eight distinct monomorphic ventricular tachycardia patterns whi...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.56.5.736
更新日期:1985-05-01 00:00:00
abstract::We have investigated the requirement for c-myc downregulation in the growth arrest of vascular smooth muscle cells (VSMCs). Rat VSMCs were infected with a retrovirus vector directing constitutive expression of either the complete human c-Myc protein (VSM-myc cells) or the c-Myc deletion mutant D106-143, which is inact...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.74.3.525
更新日期:1994-03-01 00:00:00
abstract::The effects of acute hypoxemia and hypercapnic acidosis were examined in five unanesthetized dogs in which sodium intake was controlled at 80 mEq/24 hours for 4 days prior to study. Each animal was studied during combined acute hypoxemia and hypercapnic acidosis (Pao2 = 36 +/- 1 mm Hg, Paco2 = 52 +/- 1 mm Hg, pH = 7.1...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.53.2.202
更新日期:1983-08-01 00:00:00
abstract:RATIONALE:Peroxisome proliferator-activated receptor (PPAR)γ agonists attenuate atherosclerosis and abdominal aortic aneurysms (AAAs). PPARγ, a nuclear receptor, is expressed on many cell types including smooth muscle cells (SMCs). OBJECTIVE:To determine whether a PPARγ agonist reduces angiotensin II (Ang II)-induced ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.110.219089
更新日期:2010-10-15 00:00:00
abstract::To investigate the possible contributions of cardiac volume overload and cardiac sympathetic hyperactivity in the effects of sodium on cardiac mass, we evaluated the effects of treatment with saline (1%) and deoxycorticosterone acetate + saline (DOCA/saline) for 10 days and 3 and 6 weeks on ventricular anatomy and int...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.68.3.745
更新日期:1991-03-01 00:00:00
abstract::Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited disease characterized by life threatening arrhythmias and mutations in the gene encoding the ryanodine receptor (RyR2). Disagreement exists on whether (1) RyR2 mutations induce abnormal calcium transients in the absence of adrenergic stimulat...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000235869.50747.e1
更新日期:2006-08-04 00:00:00
abstract::The dynamic interaction of simultaneously changing heart period and single vagal stimuli on atrioventricular conduction (AV interval) was quantified by subtracting the vagally induced responses of the paced heart preparation from those of the unpaced heart preparation. This difference was significantly greater (P less...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.40.1.81
更新日期:1977-01-01 00:00:00
abstract:RATIONALE:During the transition from compensated hypertrophy to heart failure, the signaling between L-type Ca(2+) channels in the cell membrane/T-tubules and ryanodine receptors in the sarcoplasmic reticulum becomes defective, partially because of the decreased expression of a T-tubule-sarcoplasmic reticulum anchoring...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.112.300806
更新日期:2013-02-15 00:00:00