Abstract:
RATIONALE:A better understanding of the mechanism underlying skeletal muscle repair is required to develop therapies that promote tissue regeneration in adults. Hedgehog signaling has been shown previously to be involved in myogenesis and angiogenesis: 2 crucial processes for muscle development and regeneration. OBJECTIVE:The objective of this study was to identify the role of the hedgehog transcription factor Gli3 in the cross-talk between angiogenesis and myogenesis in adults. METHODS AND RESULTS:Using conditional knockout mice, we found that Gli3 deficiency in endothelial cells did not affect ischemic muscle repair, whereas in myocytes, Gli3 deficiency resulted in severely delayed ischemia-induced myogenesis. Moreover, angiogenesis was also significantly impaired in HSA-Cre(ERT2); Gli3(Flox/Flox) mice, demonstrating that impaired myogenesis indirectly affects ischemia-induced angiogenesis. The role of Gli3 in myocytes was then further investigated. We found that Gli3 promotes myoblast differentiation through myogenic factor 5 regulation. In addition, we found that Gli3 regulates several proangiogenic factors, including thymidine phosphorylase and angiopoietin-1 both in vitro and in vivo, which indirectly promote endothelial cell proliferation and arteriole formation. In addition, we found that Gli3 is upregulated in proliferating myoblasts by the cell cycle-associated transcription factor E2F1. CONCLUSIONS:This study shows for the first time that Gli3-regulated postnatal myogenesis is necessary for muscle repair-associated angiogenesis. Most importantly, it implies that myogenesis drives angiogenesis in the setting of skeletal muscle repair and identifies Gli3 as a potential target for regenerative medicine.
journal_name
Circ Resjournal_title
Circulation researchauthors
Renault MA,Vandierdonck S,Chapouly C,Yu Y,Qin G,Metras A,Couffinhal T,Losordo DW,Yao Q,Reynaud A,Jaspard-Vinassa B,Belloc I,Desgranges C,Gadeau APdoi
10.1161/CIRCRESAHA.113.301546subject
Has Abstractpub_date
2013-10-25 00:00:00pages
1148-58issue
10eissn
0009-7330issn
1524-4571pii
CIRCRESAHA.113.301546journal_volume
113pub_type
杂志文章abstract::It has been postulated that cardiopulmonary baroreceptor unloading in humans results in nonuniform activation of the sympathetic nervous system. We reasoned that simultaneous measurements of arterial and venous norepinephrine (NE) spillover and clearance (using NE kinetics), muscle sympathetic neural activity (using m...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.66.6.1720
更新日期:1990-06-01 00:00:00
abstract::Anisotropic impulse conduction was studied in neonatal rat heart cell monolayers produced by culturing cells on a growth-directing substrate of collagen. Monolayers consisting of parallel-oriented cells without visible intercellular clefts were selected for experiments; cell lengths and widths were 65.8 +/- 12.5 and 1...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.75.3.591
更新日期:1994-09-01 00:00:00
abstract::The blood pressure of rabbits with chronic one-kidney hypertension can be lowered to normal by immunization with hog kidney cortex preparations that do not contain renin, thus providing evidence for a new factor essential for the maintenance of an elevated blood pressure. A search for the new factor has led to the dis...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.40.2.143
更新日期:1977-02-01 00:00:00
abstract::Although clinical trials of cell-based approaches to cardiovascular disease have yielded some promising results, no cell-based therapy has achieved regulatory approval for a cardiovascular indication. To broadly assess the challenges to regulatory approval and identify strategies to facilitate this goal, the Cardiac S...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.118.313261
更新日期:2018-08-03 00:00:00
abstract::Elastance-resistance [E(t)-R] representations of the left ventricle (LV) were evaluated for their ability to reproduce instantaneous pressure [P(t)] and outflow [Q(t)]. Experiments were performed in open-chest rats. P(t) and Q(t) were measured during steady-state ejecting beats and during a beat in which the aorta was...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.66.1.218
更新日期:1990-01-01 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::The molecular identity of receptor-operated, nonselective cation channels (ROCs) of vascular smooth muscle (VSM) cells is not known for certain. Mammalian homologues of the Drosophila canonical transient receptor potential channels (TRPCs) are possible candidates. This study tested the hypothesis that heteromultimeric...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000226495.34949.28
更新日期:2006-06-23 00:00:00
abstract::Brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) are novel natriuretic peptides, originally isolated from porcine brain. Similar to atrial natriuretic peptide (ANP), BNP is also synthesized in and secreted from cardiocytes, but CNP is not expressed at significant levels in normal adult myocardium. ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.71.1.9
更新日期:1992-07-01 00:00:00
abstract::Although the ultrasonic pulsatility index (PI) is used as a test of arterial inflow, the relationship between proximal arterial stenosis and PI has not been fully evaluated. In a series of experiments on dogs, over 200 measurements of pressure, flow (using an indwelling electromagnetic flowmeter), and PI were made dis...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.46.4.470
更新日期:1980-04-01 00:00:00
abstract:RATIONALE:Individuals with naturally occurring loss-of-function proprotein convertase subtilisin/kexin type 9 (PCSK9) mutations experience reduced low-density lipoprotein cholesterol levels and protection against cardiovascular disease. OBJECTIVE:The goal of this study was to assess whether genome editing using a clus...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.115.304351
更新日期:2014-08-15 00:00:00
abstract::Hemodynamics play an important role in cardiovascular development, and changes in blood flow can cause congenital heart malformations. The endothelium and endocardium are subjected to mechanical forces, of which fluid shear stress is correlated to blood flow velocity. The shear stress responsive genes lung Krüppel-lik...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000171901.40952.0d
更新日期:2005-06-24 00:00:00
abstract::Heme oxygenase (HO) is a cytoprotective enzyme that degrades heme (a potent oxidant) to generate carbon monoxide (a vasodilatory gas that has anti-inflammatory properties), bilirubin (an antioxidant derived from biliverdin), and iron (sequestered by ferritin). Because of properties of HO and its products, we hypothesi...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/hh1001.091521
更新日期:2001-05-25 00:00:00
abstract:RATIONALE:Congenital heart disease (CHD) is among the most common birth defects. Most cases are of unknown pathogenesis. OBJECTIVE:To determine the contribution of de novo copy number variants (CNVs) in the pathogenesis of sporadic CHD. METHODS AND RESULTS:We studied 538 CHD trios using genome-wide dense single nucle...
journal_title:Circulation research
pub_type: 临床试验,杂志文章
doi:10.1161/CIRCRESAHA.115.304458
更新日期:2014-10-24 00:00:00
abstract::In isolated right atria of the rabbit heart, we studied the activation pattern within the sinus node, using the microelectrode technique. After the electrophysiological experiments, the preparations were subjected to a correlative morphological investigation, using light or electron microscopy. Different criteria for ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.46.1.11
更新日期:1980-01-01 00:00:00
abstract::Controversy exists regarding the mechanism by which catecholamines stimulate renin secretion in vivo. A sensitive rat kidney slice system was utilized to study the direct effects of adrenergic agonists and antagonists on renin release in vitro. Catecholamines were protected from degradation by the addition of ascorbic...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.37.3.318
更新日期:1975-09-01 00:00:00
abstract::Cellular mechanisms underlying beta-adrenergic stimulation of the arrhythmogenic transient inward current (TI) were investigated by using a two-microelectrode voltage-clamp technique in rabbit cardiac Purkinje fibers. TI induced by elevating [Ca2+]o to 30 mmol/L and substituting [Na+]o with N-methyl-D-glucamine (NMG) ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.76.4.664
更新日期:1995-04-01 00:00:00
abstract::We have previously demonstrated that urokinase-type plasminogen activator (uPA) is highly expressed in the aneurysmal segment of the abdominal aorta (AAA) in apolipoprotein E-deficient (apoE-/-) mice treated with angiotensin II (Ang II). In the present study, we tested the hypothesis that uPA is essential for AAA form...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000061571.49375.E1
更新日期:2003-03-21 00:00:00
abstract:RATIONALE:Hypoxia followed by reoxygenation promotes inflammation by activating nuclear factor κB transcription factors in endothelial cells (ECs). This process involves modification of the signaling intermediary tumor necrosis factor receptor-associated factor 6 with polyubiquitin chains. Thus, cellular mechanisms tha...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.111.300119
更新日期:2013-06-07 00:00:00
abstract::The transverse tubular system (t-system) of cardiac muscle is a structure that allows rapid propagation of excitation into the cell interior. Using 2-photon molecular excitation microscopy and digital image-processing methods, we have obtained a comprehensive overview of the t-system of rat ventricular myocytes in liv...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.84.3.266
更新日期:1999-02-19 00:00:00
abstract::Heart disease is often the end result of inherited genetic defects, which may potentially be treatable using a gene-transfer approach. Recombinant adeno-associated virus (rAAV)-mediated gene delivery has emerged as a realistic method for the treatment of such disorders. Here, we demonstrate and compare the natural aff...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000237661.18885.f6
更新日期:2006-08-18 00:00:00
abstract::Increasing attention is currently devoted to the multiple roles that pericytes (also defined as mural, Rouget, or perivascular cells) may play during angiogenesis, vascular homeostasis, and pathology. Many recent excellent reviews thoroughly address these topics (see below); hence, we will not discuss them in detail h...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.113.300203
更新日期:2013-07-19 00:00:00
abstract:RATIONALE:Chronic elevation of 3'-5'-cyclic adenosine monophosphate (cAMP) levels has been associated with cardiac remodeling and cardiac hypertrophy. However, enhancement of particular aspects of cAMP/protein kinase A signaling seems to be beneficial for the failing heart. cAMP is a pleiotropic second messenger with t...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.114.305892
更新日期:2015-09-25 00:00:00
abstract::Hibernating myocardium, characterized by reductions in flow and function at rest, has limited contractile reserve in response to increases in external workload. We hypothesized that this attenuation of function reflects an adaptive downregulation that prevents the development of metabolic evidence of ischemia during s...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.0000049104.57549.03
更新日期:2003-01-10 00:00:00
abstract::Transforming growth factor (TGF)-beta plays a major role in the development of vascular diseases. Despite the pleiotropic effects of TGF-ss on vascular smooth muscle cells (VSMCs), only a few genes have been characterized as direct targets of TGF-beta in VSMCs. Cardiac ankyrin repeat protein (CARP) has been thought to...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.88.1.30
更新日期:2001-01-19 00:00:00
abstract:RATIONALE:Proteasomal degradation is altered in many disease phenotypes including cardiac hypertrophy, a prevalent condition leading to heart failure. Our recent investigations identified heterogeneous subpopulations of proteasome complexes in the heart and implicated multiple mechanisms for their regulation. OBJECTIV...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.110.222364
更新日期:2010-10-29 00:00:00
abstract::Power ratios were derived from the principle of ultrasonic Doppler velocimetry to determine a ratio of the volume of vortices to the total vessel volume under the ultrasonic beam. This ratio also equals the ratio of the cross-sectional area of vortices to the vessel lumen. In vitro pulsatile flow experiments were perf...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.67.1.166
更新日期:1990-07-01 00:00:00
abstract::Studies were performed to determine whether an alteration in coronary vascular resistance and a reduction in the reflow phenomenon occurred in the blood-perfused, heparinized canine heart after various periods of myocaridal ischemia. Regional myocardial blood flow was measured with radioactive microspheres. Proximal l...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.36.6.771
更新日期:1975-06-01 00:00:00
abstract::Alternans in heart is important as pulsus alternans in cardiac failure and electrophysiological alternans in myocardial ischemia. The explanation of this phenomenon is still unclear. We attempted to investigate the cellular mechanisms of alternans by measuring intracellular free calcium concentration [( Ca2+]i) with t...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.66.3.585
更新日期:1990-03-01 00:00:00
abstract::A method was developed for recording isometric tension from isolated small arteries (mean internal diameter, 169 microns) and veins (mean internal diameter, 273 microns) of the term fetal lung and was then applied to the study of the mechanisms controlling perinatal pulmonary hemodynamics. The specific purpose was to ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.71.2.320
更新日期:1992-08-01 00:00:00
abstract::In vitro and in vivo evidence indicates that hemodynamic wall shear stress evokes a diversity of biological responses in vascular endothelial cells, ranging from cell shape changes to alterations in low density lipoprotein receptor expression. The signal transduction mechanisms by which the level of fluid mechanical s...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.72.4.827
更新日期:1993-04-01 00:00:00