Abstract:
RATIONALE:The vascular adventitia is a complex layer of the vessel wall consisting of vasa vasorum microvessels, nerves, fibroblasts, immune cells, and resident progenitor cells. Adventitial progenitors express the stem cell markers, Sca1 and CD34 (adventitial sca1-positive progenitor cells [AdvSca1]), have the potential to differentiate in vitro into multiple lineages, and potentially contribute to intimal lesions in vivo. OBJECTIVE:Although emerging data support the existence of AdvSca1 cells, the goal of this study was to determine their origin, degree of multipotency and heterogeneity, and contribution to vessel remodeling. METHODS AND RESULTS:Using 2 in vivo fate-mapping approaches combined with a smooth muscle cell (SMC) epigenetic lineage mark, we report that a subpopulation of AdvSca1 cells is generated in situ from differentiated SMCs. Our data establish that the vascular adventitia contains phenotypically distinct subpopulations of progenitor cells expressing SMC, myeloid, and hematopoietic progenitor-like properties and that differentiated SMCs are a source to varying degrees of each subpopulation. SMC-derived AdvSca1 cells exhibit a multipotent phenotype capable of differentiating in vivo into mature SMCs, resident macrophages, and endothelial-like cells. After vascular injury, SMC-derived AdvSca1 cells expand in number and are major contributors to adventitial remodeling. Induction of the transcription factor Klf4 in differentiated SMCs is essential for SMC reprogramming in vivo, whereas in vitro approaches demonstrate that Klf4 is essential for the maintenance of the AdvSca1 progenitor phenotype. CONCLUSIONS:We propose that generation of resident vascular progenitor cells from differentiated SMCs is a normal physiological process that contributes to the vascular stem cell pool and plays important roles in arterial homeostasis and disease.
journal_name
Circ Resjournal_title
Circulation researchauthors
Majesky MW,Horita H,Ostriker A,Lu S,Regan JN,Bagchi A,Dong XR,Poczobutt J,Nemenoff RA,Weiser-Evans MCdoi
10.1161/CIRCRESAHA.116.309322subject
Has Abstractpub_date
2017-01-20 00:00:00pages
296-311issue
2eissn
0009-7330issn
1524-4571pii
CIRCRESAHA.116.309322journal_volume
120pub_type
杂志文章abstract::Activity was recorded from physiologically identified baroreceptor or chemoreceptor fibers in carotid sinus nerves of urethane-anesthetized spontaneously breathing rabbits. A carotid sinus area was vascularly isolated so that carotid sinus pressure and perfusion medium (Locke's solution or rabbit blood) could be contr...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.69.6.1608
更新日期:1991-12-01 00:00:00
abstract::14-3-3 family members are dimeric phosphoserine-binding proteins that regulate signal transduction, apoptotic, and checkpoint control pathways. Targeted expression of dominant-negative 14-3-3eta (DN-14-3-3) to murine postnatal cardiac tissue potentiates Ask1, c-jun N-terminal kinase (JNK), and p38 mitogen-activated pr...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000104084.88317.91
更新日期:2003-11-28 00:00:00
abstract::Controversy exists whether positive end-expiratory pressure (PEEP) ventilation lowers cardiac output by reducing left ventricular preload, or by a combination of mechanisms. Sixteen open-chest dogs were instrumented for measurement of left and right ventricular pressure, aortic flow, and left ventricular dimensions. W...
journal_title:Circulation research
pub_type: 杂志文章,收录出版
doi:10.1161/01.res.49.4.1017
更新日期:1981-10-01 00:00:00
abstract::We studied baroreceptor function in dogs before and after surgical repair of coarctation of the aorta by direct recording of multifiber carotid sinus (CS) nerve activity (NA) during alteration of pulsatile arterial pressure with systemic phenylephrine and nitroprusside, and during static pressure changes using a CS po...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.48.3.365
更新日期:1981-03-01 00:00:00
abstract::In clinical trials, aldosterone antagonists decrease cardiovascular mortality and ischemia by unknown mechanisms. The steroid hormone aldosterone acts by binding to the mineralocorticoid receptor (MR), a ligand-activated transcription factor. In humans, aldosterone causes MR-dependent endothelial cell (EC) dysfunction...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.108.174235
更新日期:2008-06-06 00:00:00
abstract::Elevated plasma levels of plasminogen activator inhibitor type I (PAI-1), a significant risk factor of ischemic heart disease, are associated with insulin resistance in which insulin and transforming growth factor (TGF)-beta play a pivotal role in regulating PAI-1 production. Forkhead transcription factor FOXC2 is an ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000207407.51752.3c
更新日期:2006-03-17 00:00:00
abstract::The influence of endothelin 1 on intracellular Ca2+ transients and isometric contractions was investigated in ferret papillary muscles loaded with the Ca(2+)-regulated bioluminescent indicator aequorin. In concentrations of 3 x 10(-9) to 1 x 10(-7) M, endothelin produced dose-dependent increases in the amplitudes of b...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.69.3.582
更新日期:1991-09-01 00:00:00
abstract::The aging population is increasing in developed countries. Because the incidence of cardiac disease increases dramatically with age, it is important to understand the molecular mechanisms through which the heart becomes either more or less susceptible to stress. Cardiac aging is characterized by the presence of hypert...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.116.307474
更新日期:2016-05-13 00:00:00
abstract::The realization of regenerative cardiac medicine depends on the availability of cardiomyocytes in sufficient numbers for transplantation of cardiac tissue and the accompanying blood vessels. Embryonic stem (ES) cells, bone marrow (BM) stem cells, and tissue-derived stem cells are all potential cell sources. Although E...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/01.RES.0000218272.18669.6e
更新日期:2006-04-28 00:00:00
abstract::Cyclosporine A (CsA)-induced hypertension appears to be caused in part by neurogenic vasoconstriction, but the mechanism by which CsA activates the sympathetic nervous system is unknown. In T lymphocytes, the cellular target of CsA and the macrolide immunosuppressant FK506 (as complexes with their endogenous cytoplasm...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.73.3.596
更新日期:1993-09-01 00:00:00
abstract:RATIONALE:Vascular endothelial growth factor (VEGF) affects angiogenesis, atherosclerosis, and cancer. Although the heritability of circulating VEGF levels is high, little is known about its genetic underpinnings. OBJECTIVE:Our aim was to identify genetic variants associated with circulating VEGF levels, using an unbi...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.111.243790
更新日期:2011-08-19 00:00:00
abstract::Brugada syndrome has been linked to mutations in SCN5A. Agents that dissociate slowly from the sodium channel such as flecainide and ajmaline unmask the Brugada syndrome electrocardiogram and precipitate ventricular tachycardia/fibrillation. Lidocaine, an agent with rapid dissociation kinetics, has previously been sho...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.108.172619
更新日期:2008-08-15 00:00:00
abstract::Mast cells in rat hearts were studied quantitatively during normal postnatal growth and in two types of cardiac hypertrophy. Normally, cardiac mast cell density in 11-12-day-old animals is very low, but increases markedly in the following 2-3 weeks to its highest values, with a subsequent decline toward adult values. ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.66.2.511
更新日期:1990-02-01 00:00:00
abstract:RATIONALE:Circumstantial evidence links the development of heart failure to posttranslational modifications of mitochondrial proteins, including lysine acetylation (Kac). Nonetheless, direct evidence that Kac compromises mitochondrial performance remains sparse. OBJECTIVE:This study sought to explore the premise that ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.120.317293
更新日期:2020-09-25 00:00:00
abstract::A central role for leukocytes in neointimal hyperplasia after arterial injury is suspected. However, the relative importance of neutrophils and monocytes in balloon or stent-induced injury are not well understood, and mechanistic targeting of leukocyte recruitment or function is crude. We determined the temporal and s...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/hh0402.105956
更新日期:2002-03-08 00:00:00
abstract::The positive inotropic response to angiotensin I and II in cardiac tissue of most mammalian species, as well as the exact site in the heart for conversion of local and systemic angiotensin I into angiotensin II, remains to be elucidated. In isolated cat papillary muscles, angiotensin I and angiotensin II (0.1 nM to 1 ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.66.6.1591
更新日期:1990-06-01 00:00:00
abstract::Vascular dysfunction in diabetes is attributed to lack of bioavailable nitric oxide (NO) and is postulated as a primary cause of small vessel complications as a result of poor glycemic control. Although it has been proposed that NO is bound by red blood cells (RBCs) and can induce relaxation of blood vessels distal to...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000122044.21787.01
更新日期:2004-04-16 00:00:00
abstract:RATIONALE:Remote ischemic preconditioning (rIPC) with short episodes of ischemia/reperfusion (I/R) of an organ remote from the heart is a powerful approach to protect against myocardial I/R injury. The signal transduction pathways for the cross talk between the remote site and the heart remain unclear in detail. OBJEC...
journal_title:Circulation research
pub_type: 临床试验,杂志文章
doi:10.1161/CIRCRESAHA.114.303822
更新日期:2014-05-09 00:00:00
abstract::Choline acetyltransferase is the enzyme that catalyzes the biosynthesis of acetylcholine, the neurotransmitter of the pre- and postganglionic parasympathetic system. To assess the extent of parasympathetic innervation, enzyme activity was measured in specialized and contractile regions throughout the guinea pig heart....
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.42.5.657
更新日期:1978-05-01 00:00:00
abstract::In our morphometric study of the effects of exercise on the heart, male Wistar-Kyoto rats at 5 weeks of age were subjected daily to a moderate treadmill running program that lasted for 7 weeks. The heart responded to physical conditioning by different magnitudes of tissue growth of the right (22%) and left (7%) ventri...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.52.1.57
更新日期:1983-01-01 00:00:00
abstract::Morphometric data from stable (nonedematous) isolated dog lungs, perfused with nearly cell-free perfusates, were compared to similar stereological evaluations of isolated dog lungs after induction of severe acute hydrostatic edema. In the edematous lungs, capillary surface and volume densities were substantially incre...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.43.1.72
更新日期:1978-07-01 00:00:00
abstract::3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) can exert beneficial effects independently of serum cholesterol reduction by increasing the bioavailability of nitric oxide. However, it is unclear whether statins can exert such effects directly on cardiac myocytes and whether mitochondria...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000097262.21507.DF
更新日期:2003-10-17 00:00:00
abstract::Therapeutic angiogenesis using vascular endothelial growth factor (VEGF) is considered a promising new therapy for patients with arterial obstructive disease. Clinical improvements observed consist of improved muscle function and regression of rest pain or angina. However, direct evidence for improved vascularization,...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000133247.69803.c3
更新日期:2004-07-09 00:00:00
abstract::Diabetes mellitus has profound adverse effects on vascular and, in particular, endothelial function. Although pressure-induced constriction ("myogenic tone") is a major contributor to the regulation of blood flow, little is known about the effects of diabetes on this response. Diabetes has been shown to diminish the d...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.81.6.996
更新日期:1997-12-01 00:00:00
abstract::Nitric oxide (NO) exerts important vasodilatory, antiplatelet, antioxidant, antiadhesive, and antiproliferative effects. Although endothelium derived NO has been shown to be of prime importance in cardio- and vasculoprotection, until recently little was known about the role of platelet-derived NO. New evidence suggest...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.107.158410
更新日期:2007-09-28 00:00:00
abstract::This study addresses the structural requirements for the intracellular processing and receptor binding properties of endothelin-1 (ET-1). Point mutants of preproendothelin-1 cDNA, with replacement of the codons for Lys9 of ET-1 by ones for Ala and Glu and of Ile20 and Trp21 by ones encoding Ala, were expressed in COS-...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.77.6.1087
更新日期:1995-12-01 00:00:00
abstract::Despite improvements in the therapy of underlying heart disease, sudden cardiac death is a major cause of death worldwide. Disturbed Na and Ca handling is known to be a major predisposing factor for life-threatening tachyarrhythmias. In cardiomyocytes, many ion channels and transporters, including voltage-gated Na and...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.116.304678
更新日期:2015-06-05 00:00:00
abstract::Endothelins exert potent excitatory cardiac effects by acting on specific receptors on myocytes. In this study, we have examined the signal transduction mechanism for the chronotropic effect of endothelins in guinea pig atria. A competition binding of [125I]endothelin 1 ([125I]ET-1) using the recently developed ETA re...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.76.2.284
更新日期:1995-02-01 00:00:00
abstract::The rate of renin secretion from renal juxtaglomerular (JG) cells is the major determinant of the activity of the renin-angiotensin system. However, the mechanisms involved in the excretion and turnover of secretory granules in the JG cells remain obscure. Therefore, in the present study, the whole-cell patch-clamp te...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.84.8.929
更新日期:1999-04-30 00:00:00
abstract::The kinetics of contractions and Ca(2+) transients are slowed in myocytes from failing hearts. The mechanisms accounting for these abnormalities remain unclear. Myocardial infarction (MI) was produced by ligation of the circumflex artery in rabbits. We used confocal microscopy to record spatially resolved Ca(2+) trans...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.87.11.1040
更新日期:2000-11-24 00:00:00