Abstract：
AIMS:Smad7 plays a negative regulatory role in many inflammatory diseases, but its effect on hypertensive disease remains unknown. The present study tested the hypothesis that overexpression of Smad7 may have therapeutic potential for angiotensin II (Ang II)-mediated hypertensive cardiac remodelling. METHODS AND RESULTS:Hypertensive heart disease was induced in mice by subcutaneous infusion of Ang II for 28 days and treated with Smad7 by a non-invasive ultrasound-microbubble-mediated inducible Smad7 gene transfer. We found that cardiac Smad7 was largely reduced in the hypertensive heart and overexpression of cardiac Smad7 protected against the fall in the left ventricular (LV) ejection fraction (EF), an increase in LV mass, and cardiac inflammation and fibrosis such as up-regulation of pro-inflammatory cytokines (IL-1β, TNF-α) and fibrotic markers (collagen I, α-SMA), and infiltration of CD3(+) T cells and F4/80(+) macrophages. Further studies revealed that inactivation of the Sp1-TGF-β/Smad3-NF-κB (NF-κB, nuclear factor κB) pathways and prevention of cardiac miR-29 loss were mechanisms by which overexpression of Smad7 inhibited Ang II-mediated cardiac remodelling. Importantly, we also found that treatment with Smad7 when hypertensive cardiopathy established at day 14 halted the progression of cardiac injury by blunting the fall of EF and an increase in LV mass, and blocking TGF-β/Smad3-mediated cardiac fibrosis and NF-κB-driven inflammation. CONCLUSION:Smad7 plays a protective role in Ang II-induced cardiac remodelling via mechanisms involving the Sp1-TGF-β/Smad-NF-κB-miR-29 regulatory network. Thus, Smad7 may be a novel therapeutic agent for hypertensive cardiovascular diseases.
journal_name
Cardiovasc Resjournal_title
Cardiovascular researchauthors
Wei LH,Huang XR,Zhang Y,Li YQ,Chen HY,Yan BP,Yu CM,Lan HYdoi
10.1093/cvr/cvt151subject
Has Abstractpub_date
2013-09-01 00:00:00pages
665-73issue
4eissn
0008-6363issn
1755-3245pii
cvt151journal_volume
99pub_type
杂志文章abstract：:The effect of chronic propranolol administration (2 mg.kg-1.d-1 for 14d) and withdrawal on microvascular perfusion was studied in rabbit myocardium. Fluorescein isothiocyanate-dextran was injected into four groups of anaesthetised open chest rabbits. Fluorescent microscopy was used to identify the perfused vessels and...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/22.11.793
更新日期：1988-11-01 00:00:00
abstract：:Coronary artery disease (CAD) remains one of the most important causes of morbidity and mortality worldwide, and the availability of percutaneous or surgical revascularization procedures significantly improves survival. However, both strategies are daunted by complications which limit long-term effectiveness. In-stent...
journal_title：Cardiovascular research
pub_type： 杂志文章,评审
doi：10.1093/cvr/cvz214
更新日期：2020-03-01 00:00:00
abstract：AIM:To assess whether endothelin-1 (ET-1) induces the in vivo expression of inflammatory-related proteins, namely cyclooxygenase-2 (COX-2) and tissue factor, in the myocardium and circulating leukocytes of guinea-pigs. The involvement of platelets was also analyzed. METHODS:ET-1 (0.013 microg/min) was infused to male ...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1016/s0008-6363(02)00657-0
更新日期：2003-01-01 00:00:00
abstract：AIMS:A cytosolic calcium (Ca(2+)(i)) increase is an important activation signal for the endothelium. We investigated whether interendothelial spreading of the Ca(2+) signal via gap junctions (GJs) plays a role for the overall Ca(2+)(i) increase in response to vasoactive agonists. METHODS AND RESULTS:In human umbilical...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/cvr345
更新日期：2012-03-01 00:00:00
abstract：OBJECTIVE:To study the effect of cardiac contraction on left coronary artery pressure-flow relations at different vascular volumes and to compare these relations in the beating heart with those in the heart arrested in systole and diastole. METHODS:Maximally vasodilated, Tyrode perfused, rabbit hearts (n = 6) with an ...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1016/s0008-6363(98)00119-9
更新日期：1998-10-01 00:00:00
abstract：STUDY OBJECTIVE:The objectives were (a) to describe the effects of vasoactive drugs in normal rats upon cardiovascular function assessed by computing aortic haemodynamic power and input impedance, each separated into their component parts, and (b) to study the relationship between left ventricular pulsatile power outpu...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/25.11.923
更新日期：1991-11-01 00:00:00
abstract：:Atherosclerosis is considered a to be multifactorial disease driven by inflammatory reactions. The process of inflammation also contributes to the pathogenesis of acute atherothrombotic events. C-reactive protein (CRP) is an acute phase protein and its concentration in serum reflects the inflammatory condition of the ...
journal_title：Cardiovascular research
pub_type： 杂志文章,评审
doi：10.1016/j.cardiores.2006.03.004
更新日期：2006-07-01 00:00:00
abstract：AIMS:Arrhythmias and sudden cardiac death (SCD) occur commonly in patients with heart failure. We found T-box 5 (TBX5) dysregulated in ventricular myocardium from heart failure patients and thus we hypothesized that TBX5 reduction contributes to arrhythmia development in these patients. To understand the underlying mec...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/cvaa239
更新日期：2020-08-10 00:00:00
abstract：OBJECTIVE:Cardiac parasympathetic nerve activity is reduced in most cardiovascular disease states, and this may contribute to enhanced cardiac sympathetic responsiveness. Disruption of inhibitory G-proteins (Gi) ablates the cholinergic pathway and increases cardiac endothelial nitric oxide (NO) synthase (eNOS) expressi...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1016/j.cardiores.2005.04.034
更新日期：2005-09-01 00:00:00
abstract：:Zero drift may be a cause of imprecision when micromanometer tipped catheters are used for intravascular pressure measurement over long periods of time. Drift of only a few mm Hg may represent a significant error when accurate recording of low vascular pressures is required. To overcome this problem a micromanometer t...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/23.2.152
更新日期：1989-02-01 00:00:00
abstract：OBJECTIVES:To characterize the 'anti-ischemic' effects of adenosine metabolism inhibition in ischemic-reperfused myocardium. METHODS:Perfused C57/B16 mouse hearts were subjected to 20 min ischemia 40 min reperfusion in the absence or presence of adenosine deaminase inhibition (50 microM erythro-2-(2-hydroxy-3-nonyl)ad...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1016/s0008-6363(01)00360-1
更新日期：2001-10-01 00:00:00
abstract：OBJECTIVE:To examine whether altered PCO2 or HCO3- at normal pH potentiate agonist-induced vasoconstriction of small pulmonary arteries, and if so to determine the mechanism. METHODS:Small intrapulmonary arteries (IPA) from rats were mounted on a myograph and PGF2alpha (3 microM)-induced tension recorded before and 40...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1016/j.cardiores.2004.10.038
更新日期：2005-02-01 00:00:00
abstract：AIMS:Diabetes impinges upon mechanisms of cardiovascular repair. However, the biochemical adaptation of cardiac stem cells to sustained hyperglycaemia remains largely unknown. Here, we investigate the molecular targets of high glucose-induced damage in cardiac progenitor cells (CPCs) from murine and human hearts and at...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/cvs291
更新日期：2013-01-01 00:00:00
abstract：AIMS:Acute migraine attack in familial hemiplegic migraine type 2 (FHM2) patients is characterized by sequential hypo- and hyperperfusion. FHM2 is associated with mutations in the Na, K-ATPase α2 isoform. Heterozygous mice bearing one of these mutations (α2+/G301R mice) were shown to have elevated cerebrovascular tone ...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/cvz306
更新日期：2020-10-01 00:00:00
abstract：AIMS:Sulfur dioxide (SO₂) is an air pollutant that impedes neonatal development and induces adverse cardiorespiratory health effects, including tachycardia. Here, an animal model was developed that enabled characterization of (i) in vivo alterations in heart rate and (ii) altered activity in brainstem neurons that cont...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/cvt057
更新日期：2013-07-01 00:00:00
abstract：OBJECTIVES:The aim was to determine the effect and mechanisms by which myocyte stretch interacts with the prolongation of action potential duration (APD) by the class III antiarrhythmic agent E-4031. METHODS:Action potentials and whole-cell currents were measured in isolated guinea pig ventricular myocytes with a patc...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：
更新日期：1996-02-01 00:00:00
abstract：OBJECTIVE:We tested the hypothesis that simultaneous inhibition of the endothelial integrin alpha(v)beta(3) and the platelet glycoprotein IIb/IIIa receptor will substantially reduce infarct size in a model of acute coronary thrombosis and primary angioplasty. METHODS:Dogs were subjected to thrombus formation in the le...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1016/j.cardiores.2005.01.016
更新日期：2005-06-01 00:00:00
abstract：AIMS:Our previous studies demonstrated that inflammation contributes to atherosclerosis through disruption of the low density lipoprotein receptor (LDLr) pathway. However, this effect is overridden by rapamycin, which is an inhibitor of mammalian target of rapamycin (mTOR). This study investigated the role of the mTOR ...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/cvt203
更新日期：2013-12-01 00:00:00
abstract：OBJECTIVE:The primary aim of this study was to investigate whether activation of Na influx via voltage-gated Na channels can elevate sub-sarcolemmal ('fuzzy-space') [Na] and transiently activate Na/K pump current (I(p)). METHODS AND RESULTS:Initially, Na/K pump activity was characterised in whole-cell voltage-clamped ...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1016/s0008-6363(02)00645-4
更新日期：2003-03-15 00:00:00
abstract：AIMS:Sphingosine-1-phosphate (S1P), a key regulator of vascular homeostasis and angiogenesis, promotes endothelial cell migration via stimulation of phosphoinositide 3-kinase (PI3K). The aim of this study was to identify the role of PI3Kbeta and gamma isoforms and their downstream effector pathways in mediating endothe...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/cvn159
更新日期：2008-10-01 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：:Cardiomyocytes are long-lived post-mitotic cells with limited regenerative capacity. Proper cardiomyocyte function depends critically on the maintenance of a healthy homeostasis of protein expression, folding, assembly, trafficking, function, and degradation, together commonly referred to as proteostasis. Impairment o...
journal_title：Cardiovascular research
pub_type： 杂志文章,评审
doi：10.1093/cvr/cvv265
更新日期：2016-04-01 00:00:00
abstract：AIMS:Previous studies on the role of stem cell factor (SCF) in endothelial progenitor cell (EPC)-mediated neovascularization have focused on the EPC mobilization and homing process. However, the direct effects of SCF on neovascularization activity of EPCs have not been characterized. We sought to determine whether SCF ...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/cvr161
更新日期：2011-10-01 00:00:00
abstract：OBJECTIVE:Atrial remodeling contributes to the maintenance of atrial fibrillation (AF) in several cardiac disorders. There is evidence that angiotensin-converting enzyme (ACE) inhibitors reduce the prevalence of AF in patients with congestive heart failure (CHF). There have been no studies performed to assess the effec...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1016/s0008-6363(02)00243-2
更新日期：2002-05-01 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：OBJECTIVE:The mechanism of spontaneous myogenic tone was investigated in isolated arteriolar segments. METHODS:Arterioles were isolated from rat cremaster muscle. Segments were endothelium-denuded and mounted in a pressure myograph at 75 mmHg. Under this condition, segments spontaneously constricted from a passive dia...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1016/s0008-6363(98)00161-8
更新日期：1999-01-01 00:00:00
abstract：OBJECTIVE:The aims of the study were to determine the effect of chronic pressure overload of the left ventricle on the density and distribution of neuropeptide-Y-like immunoreactive (NPY-LI) nerve fibres in heart and to compare any changes to those observed in adrenergic nerve fibres, identified by dopamine beta-hydrox...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/27.3.494
更新日期：1993-03-01 00:00:00
abstract：:Exaggerated cardiovascular responsiveness is common in young men and may cause non-specific symptoms and poor performance. Conventional autonomic function tests are not clinically useful. We have therefore designed a thermal entrainment method to evaluate sympathetic and parasympathetic cardiovascular function in subj...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/23.3.262
更新日期：1989-03-01 00:00:00
abstract：OBJECTIVE:We have attempted to demonstrate the induction of inducible nitric oxide synthase in human vascular tissue and define the capacity of different cytokines to induce this enzyme. METHODS:Segments of human arteries were stimulated with lipopolysaccharide (10 micrograms/ml), interleukin-1 beta (5 U/ml), tumor ne...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1016/s0008-6363(98)00054-6
更新日期：1998-06-01 00:00:00
abstract：OBJECTIVE:Polymorphic ventricular tachycardias (PVT) occur spontaneously in canine hearts under the combination of D-sotalol (S), bradycardia and phenylephrine (PE). We investigated the hypotheses that: (1) the activation patterns of the initial PVT beats would be consistent with an origin in the ventricular conduction...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1016/s0008-6363(98)00036-4
更新日期：1998-06-01 00:00:00
