Abstract:
:The second messenger cyclic guanosine 3'5' monophosphate (cGMP) and its downstream effector protein kinase G (PKG) have been discovered more than 40 years ago. In vessels, PKG1 induces smooth muscle relaxation in response to nitric oxide signalling and thus lowers systemic and pulmonary blood pressure. In platelets, PKG1 stimulation by cGMP inhibits activation and aggregation, and in experimental models of heart failure (HF), PKG1 activation by inhibiting cGMP degradation is protective. The net effect of the above-mentioned signalling is cardiovascular protection. Yet, while modulation of cGMP-PKG has entered clinical practice for treating pulmonary hypertension or erectile dysfunction, translation of promising studies in experimental HF to clinical success has failed thus far. With the advent of new technologies, novel mechanisms of PKG regulation, including mechanosensing, redox regulation, protein quality control, and cGMP degradation, have been discovered. These novel, non-canonical roles of PKG1 may help understand why clinical translation has disappointed thus far. Addressing them appears to be a requisite for future, successful translation of experimental studies to the clinical arena.
journal_name
Cardiovasc Resjournal_title
Cardiovascular researchauthors
Rainer PP,Kass DAdoi
10.1093/cvr/cvw107subject
Has Abstractpub_date
2016-07-15 00:00:00pages
154-62issue
2eissn
0008-6363issn
1755-3245pii
cvw107journal_volume
111pub_type
杂志文章,评审abstract::Hydrogen sulfide (H2S), as a gaseous signalling molecule, has been found to play important roles in postconditioning (PostC)-induced cardioprotection. Similar to nitric oxide (NO)-mediated protein S-nitrosylation (SNO), recent studies suggest that H2S could regulate protein function through another redox-based post-tr...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvw037
更新日期:2016-05-01 00:00:00
abstract:AIMS:in this study, we attempted to detect a recent myocardial ischaemic event using ultrasound molecular imaging (UMI) with microbubbles (MB) targeted to intercellular adhesion molecule-1 (ICAM-1) in the late phase of reperfusion. METHODS AND RESULTS:we created a myocardial ischaemia-reperfusion model in 60 C57/BL ma...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvq269
更新日期:2011-01-01 00:00:00
abstract:STUDY OBJECTIVE:The aim was to determine if the adaptational process of the cardiac calcium channel to pressure overload observed in rat heart also occurs in species characterised by a higher sensitivity to external calcium than in the rat. This adaptation occurs via a maintained density of dihydropyridine receptors an...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/25.10.875
更新日期:1991-10-01 00:00:00
abstract:OBJECTIVE:In heart failure (HF), the generation of reactive oxygen species (ROS) is enhanced. It was shown that failing cardiac myocytes are more susceptible to ROS-induced damage, possibly due to increased expression of the sarcolemmal Na-Ca exchanger (NCX). METHODS:We investigated the consequences of increased expre...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2003.08.006
更新日期:2003-11-01 00:00:00
abstract:OBJECTIVE:Previous investigations have shown the effectiveness of sustained intra- or extravascular administration of vascular endothelial growth factor (VEGF) in chronic myocardial ischemia in improvement of left ventricular function. The present investigations were undertaken in order to evaluate efficacy of a single...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(98)00136-9
更新日期:1998-11-01 00:00:00
abstract::The intrinsic ability of resistance arteries to respond to transmural pressure is the single most important determinant of their function. Despite an ever-growing catalogue of signalling pathways that underlie the myogenic response, it remains an enigmatic mechanism. The myogenic response's mechanistic diversity has l...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvs345
更新日期:2013-03-01 00:00:00
abstract:AIMS:Expression of extracellular matrix protein CCN1 is induced in end-stage ischaemic cardiomyopathy in humans, and after cardiac ischaemia and reperfusion in experimental animal models. Despite its well-documented angiogenic activities, CCN1 increases the cytotoxicities of the tumour necrosis factor family cytokines,...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvt001
更新日期:2013-04-01 00:00:00
abstract:AIM:Atrial fibrosis, one of the most striking features in the pathology of atrial fibrillation (AF), is promoted by local and systemic inflammation. Electrophilic fatty acid nitroalkenes, endogenously generated by both metabolic and inflammatory reactions, are anti-inflammatory mediators that in synthetic form may be u...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvv254
更新日期:2016-01-01 00:00:00
abstract:AIMS:Our objective was to explore the functional interdependence of protein kinase A (PKA) phosphorylation with binding of modulatory FK506 binding proteins (FKBP12/12.6) to the ryanodine receptor (RyR). RyR type 1 or type 2 was prepared from rabbit skeletal muscle or pig cardiac muscle, respectively. In heart failure,...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvp273
更新日期:2010-01-01 00:00:00
abstract::The static elastic properties of the aorta ad systolic blood pressure in the caudal artery have been measured in 55 spontaneously hypertensive rats of the AS strain. Animals were divided into five groups and treated from the age of 4 to 12 weeks as follows: (1) 0.25 mm silver clip positioned around the right renal art...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/15.7.373
更新日期:1981-07-01 00:00:00
abstract:AIMS:Bone marrow (BM) progenitor cells may contribute to vascular remodelling. The present study aimed to investigate the contribution of BM-derived CXCR4(+) (a CXC chemokine receptor) and PDGFRbeta(+) (platelet-derived growth factor receptor beta) progenitor cells in hypoxia-induced muscularization of alveolar arterio...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvq147
更新日期:2010-09-01 00:00:00
abstract:AIMS:Heart failure is associated with deficient endothelial nitric oxide (NO) production as well as increased oxidative stress and accelerated NO degradation. The aim of this study was to evaluate platelet NO biosynthesis and superoxide anion (O(2)(-)) production in patients with heart failure. METHODS AND RESULTS:In ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvr115
更新日期:2011-09-01 00:00:00
abstract:OBJECTIVE:Recent studies indicate that endothelial type nitric oxide synthase (NOS3) modulates cardiac systolic and diastolic function and the inotropic responsiveness to beta-adrenergic agonists, and may affect myocardial oxygen consumption. Although NOS3 is a constitutive protein, its levels of expression can be modi...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(98)00059-5
更新日期:1998-06-01 00:00:00
abstract:AIMS:Fibromuscular dysplasia (FMD) and spontaneous coronary artery dissection (SCAD) are related, non-atherosclerotic arterial diseases mainly affecting middle-aged women. Little is known about their physiopathological mechanisms. We aimed to identify rare genetic causes to elucidate molecular mechanisms implicated in ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvaa161
更新日期:2020-06-12 00:00:00
abstract:AIMS:Neovascularization is an important element of long-term functional recovery during chronic ischaemia. We postulated that haeme oxygenase (HO) is required for progenitor cell recruitment, neovascularization, and blood flow recovery after critical hindlimb ischaemia (HLI). METHODS AND RESULTS:The femoral artery was...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvm107
更新日期:2008-05-01 00:00:00
abstract:OBJECTIVE:The aim was to investigate the effect on the coronary network of the interaction between high arterial blood oxygen tension (PaO2) and stimulation by the alpha adrenergic agonist phenylephrine or by serotonin in an isolated, blood perfused rabbit heart preparation. METHODS:Fresh pig erythrocytes in Krebs-Hen...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/28.9.1326
更新日期:1994-09-01 00:00:00
abstract::Studies were carried out in four different canine preparations to determine the effect of collateral flow on early changes induced by acute segmental ischaemia. The results of these experiments indicated that collateral flow provided a limited and variable amount of protection. When collateral flow was eliminated, myo...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/12.5.309
更新日期:1978-05-01 00:00:00
abstract:OBJECTIVE:To determine the role of calcineurin and Src tyrosine kinase in the regulation of inducible nitric oxide synthase (iNOS) expression and protection in cardiomyocytes. METHODS:iNOS expression was studied in isolated neonatal rat ventricular myocyte cultures in response to bacterial lipopolysaccharide (LPS) or ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2006.05.026
更新日期:2006-09-01 00:00:00
abstract:AIMS:Therapeutic use of sulfhydrylated inhibitor S-zofenopril has raised different hypotheses regarding the role played by its thiol group in the beneficial clinical effects exerted compared with other angiotensin-converting enzyme (ACE) inhibitors. Here, we investigated hydrogen sulfide (H2S) pathway as accountable fo...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvu026
更新日期:2014-04-01 00:00:00
abstract::Computation of indices of regional myocardial contractility such as the shortening, or the work done by or on a segment of myocardium in a single cardial cycle is tedious to perform manually, and complex interfacing and software is needed for digital computation. We describe the principles of an on-line, analogue devi...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/17.12.767
更新日期:1983-12-01 00:00:00
abstract:AIMS:Polyunsaturated fatty n-3 acids (PUFAs) have been reported to exhibit antiarrhythmic properties. However, the mechanisms of action remain unclear. We studied the electrophysiological effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on IKs, and on the expression and location of Kv7.1 and KCNE1....
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvu250
更新日期:2015-02-01 00:00:00
abstract:AIMS :Activation of the angiotensin (Ang)-(1-7)/Mas receptor (R) axis protects from sympathetic overactivity. Endocytic trafficking is an essential process that regulates receptor (R) function and its ultimate cellular responses. We investigated whether the blunted responses to Ang-(1-7) in hypertensive rats are associ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvz332
更新日期:2020-10-01 00:00:00
abstract::A recently developed highly sensitive radioimmunoassay method for detecting plasma kinin was used to re-evaluate the results of previous studies, in which plasma kinin had been measured with a bioassay method. To clarify the mechanism of plasma kinin release in global myocardial ischaemia the left main coronary artery...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/21.6.428
更新日期:1987-06-01 00:00:00
abstract::Although substantial information has accumulated over the past decade, many gaps remain in our understanding of the regulation of contractility and modulation of inotropic responsiveness in the developing heart. There are several important problems facing investigators in the field of developmental cardiology. Respons...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/26.1.3
更新日期:1992-01-01 00:00:00
abstract::In this study we report about the modulation of connexin45 (Cx45) gap junction channel properties by phosphorylation of the connexin molecules through different protein kinases. Phosphorylation of Cx45 was studied in HeLa cells transfected with mouse Cx45 (mCx45). Using Western blotting (WB) and immunocytochemistry, t...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(00)00047-x
更新日期:2000-06-01 00:00:00
abstract:AIMS:Alteration of connexin43 (Cx43)-mediated intercellular communication is known to promote susceptibility to ventricular tachyarrhythmias. However, the precise mechanism of the altered Cx43 responsible for arrhythmogenesis remains unclear. We sought to understand changes in impulse propagation of ventricular myocyte...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvn084
更新日期:2008-07-01 00:00:00
abstract:OBJECTIVE:To characterise the effect of coronary intra-arterial thrombosis upon the downstream vascular bed. BACKGROUND:The vascular response downstream from a coronary intra-arterial thrombus has not previously been characterised. We postulated that downstream vasoconstriction might result from the presence of endoth...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:
更新日期:1995-11-01 00:00:00
abstract:OBJECTIVE:Previous studies showed that treatment of hearts with nisoldipine improves recovery of cardiac function following ischaemia, improves reperfusion, and reduces the constrictor sensitivity to endothelin. The aim of the present study was to assess the reduction in vasodilator responses that occurs following isch...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/27.6.990
更新日期:1993-06-01 00:00:00
abstract::Cardiac accumulation patterns of pyrophosphate labelled with techetium-99m (TcPyP) in rats one hour to 7 days after coronary artery ligation were studied by light microscopy, myocardial scintigraphy, imaging the isolated heart and by direct measurement of tissue activity. Results suggest that myocardial cells taking u...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/14.6.352
更新日期:1980-06-01 00:00:00
abstract::The purpose of this review is to give an integrative view of the effect of stretch on the myocardium from ventricular function changes to cellular and molecular mechanisms. The general approach will be to discuss the cellular and molecular events which can explain the findings obtained in the whole ventricle. Followin...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:
更新日期:1996-07-01 00:00:00