Abstract:
:A large body of data gathered over the past couple of years has identified the peroxisome proliferator-activated receptors (PPAR) alpha, gamma, and beta/delta as transcription factors exerting modulatory actions in vascular cells. PPARs, which belong to the nuclear receptor family of ligand-activated transcription factors, were originally described as gene regulators of various metabolic pathways. Although the PPARalpha, gamma, and beta/delta subtypes are approximately 60% to 80% homologous in their ligand- and DNA-binding domains, significant differences in ligand and target gene specificities are observed. PPARalpha is activated by polyunsaturated fatty acids and oxidized derivatives and by lipid-modifying drugs of the fibrate family, including fenofibrate or gemfibrozil. PPARalpha controls expression of genes implicated in lipid metabolism. PPARgamma, in contrast, is a key regulator of glucose homeostasis and adipogenesis. Ligands of PPARgamma include naturally occurring FA derivatives, such as hydroxyoctadecadienoic acids (HODEs), prostaglandin derivatives such as 15-deoxyDelta12,14-prostaglandin J2, and glitazones, insulin-sensitizing drugs presently used to treat patients with type 2 diabetes. Ligands for PPARbeta/delta are polyunsaturated fatty acids, prostaglandins, and synthetic compounds, some of which are presently in clinical development. PPARbeta/delta stimulates fatty acid oxidation predominantly acting in muscle. All PPARs are expressed in vascular cells, where they exhibit antiinflammatory and antiatherogenic properties. In addition, studies in various animal models as well as clinical data suggest that PPARalpha and PPARgamma activators can modulate atherogenesis in vivo. At present, no data are available relating to possible effects of PPARbeta/delta agonists on atherogenesis. Given the widespread use of PPARalpha and PPARgamma agonists in patients at high risk for cardiovascular disease, the understanding of their function in the vasculature is not only of basic interest but also has important clinical implications. This review will focus on the role of PPARs in the vasculature and summarize the present understanding of their effects on atherogenesis and its cardiovascular complications.
journal_name
Circ Resjournal_title
Circulation researchauthors
Marx N,Duez H,Fruchart JC,Staels Bdoi
10.1161/01.RES.0000127122.22685.0Asubject
Has Abstractpub_date
2004-05-14 00:00:00pages
1168-78issue
9eissn
0009-7330issn
1524-4571pii
94/9/1168journal_volume
94pub_type
杂志文章,评审abstract::Oxidized low-density lipoproteins increase arginase activity and reciprocally decrease endothelial NO in human aortic endothelial cells. Here, we demonstrate that vascular endothelial arginase activity is increased in atherogenic-prone apolipoprotein E-null (ApoE(-/-)) and wild-type mice fed a high cholesterol diet. I...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.107.169573
更新日期:2008-04-25 00:00:00
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. OBJEC...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.113.301546
更新日期:2013-10-25 00:00:00
abstract:RATIONALE:PCSKs (Proprotein convertase subtilisins/kexins) are a protease family with unknown functions in vasculature. Previously, we demonstrated PCSK6 upregulation in human atherosclerotic plaques associated with smooth muscle cells (SMCs), inflammation, extracellular matrix remodeling, and mitogens. OBJECTIVE:Here...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.119.316063
更新日期:2020-02-28 00:00:00
abstract::Inhibition of vascular smooth muscle (VSM) delayed rectifier K+ channels (K(DR)) by 4-aminopyridine (4-AP; 200 micromol/L) or correolide (1 micromol/L), a selective inhibitor of Kv1 channels, enhanced myogenic contraction of rat mesenteric arteries (RMAs) in response to increases in intraluminal pressure. The molecula...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000154070.06421.25
更新日期:2005-02-04 00:00:00
abstract::First-generation, E1-deleted adenoviral vectors (E1-AV) can transduce the vascular endothelium with high efficiency, but their use is limited by the resulting acute endothelial injury and the long-term development of intimal hyperplasia. To reduce the impact of viral proteins on the gene-modified cells, a second-gener...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/hh0901.090926
更新日期:2001-05-11 00:00:00
abstract:RATIONALE:Diabetes mellitus is frequently complicated by cardiovascular disease, such as vascular calcification and endothelial dysfunction, which have been associated with bone morphogenetic proteins (BMPs). OBJECTIVE:To determine whether hyperglycemia in vitro and diabetes in vivo promote vascular BMP activity and c...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.110.236596
更新日期:2011-02-18 00:00:00
abstract::Fibroblast growth factor-1 (FGF-1), a prototype member of the heparin-binding growth factor family, is a potent mitogen for vascular endothelial cells and a variety of other cell types. FGF-1 can induce the expression of the platelet-derived growth factor-A chain (PDGF-A) gene in endothelial cells; however, the underl...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.81.2.282
更新日期:1997-08-01 00:00:00
abstract::Cardiac allograft vasculopathy (CAV) continues to be a major cause of late graft failure after cardiac transplantation. We have demonstrated that Rho-kinase, an effector of the small GTPase Rho, plays an important role in the pathogenesis of arteriosclerosis. In this study, we examined whether the Rho-kinase-mediated ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000107196.21335.2B
更新日期:2004-01-09 00:00:00
abstract::It is known that branching strands of cardiac tissue can form a substrate for very slow conduction. The branches slow conduction by acting as current loads drawing depolarizing current from the main strand ("pull" effect). It has been suggested that, upon depolarization of the branches, they become current sources rei...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/hh2101.098442
更新日期:2001-10-26 00:00:00
abstract::The effects of Bay K 8644 on the high-threshold calcium channel was investigated by means of the whole-cell patch-clamp technique in single guinea pig ventricular myocytes. The goal of the experiments was to characterize the inhibitory effects of Bay K 8644 on the calcium channel, and identify the factors that influen...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.62.1.97
更新日期:1988-01-01 00:00:00
abstract::Genetically hypertensive (GH) rats of the New Zealand strain and normotensive (N) rats were sympathectomized from birth with 6-hydroxydopamine (100 mg/kg,s.c, on alternate days, seven treatments). In adult treated rats from each strain (GHTr and NTr), blood pressure was lower than normal. Functional tests and electron...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.43.2.293
更新日期:1978-08-01 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::Whole-cell Ca2+ channel currents were recorded from isolated single canine Purkinje and ventricular cells to determine whether there were multiple types of Ca2+ channels in these two cell types, as in many other excitable tissues. The experimental conditions were such that currents other than Ca2+ channel currents wer...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.65.6.1735
更新日期:1989-12-01 00:00:00
abstract::Previous studies have shown that integrin activation and fluid shear stress can modulate the activity of sterol regulatory element binding proteins (SREBPs) in vascular endothelial cells. We investigated the role of small GTPase Rho-mediated signal transduction pathway in this mode of SREBP activation. Fluid shear str...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000078780.65824.8B
更新日期:2003-06-27 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::Postnatal development of the mammalian heart is associated with changes in the population of isoforms of the thin filament proteins. We correlated the change in thin filament proteins, which occur in rabbit hearts between 5 days and 22 days of age, with changes in Ca2+ dependence of myofibrillar ATPase activity, force...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.66.5.1204
更新日期:1990-05-01 00:00:00
abstract::The mechanism of propranolol-inhibited sarcolemmal membrane lipid peroxidation was investigated by electron spin resonance spin-trapping technique using 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) and 2-methyl-2-nitrosopropane (MNP). Highly purified canine myocytic sarcolemma were peroxidized by a superoxide-driven (from ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.65.4.1151
更新日期:1989-10-01 00:00:00
abstract::Red blood cells and lysate products (erythrolysate) are observed consistently in lymph draining acute and chronic inflammatory reactions and from tissues subjected to trauma or surgical procedures. Using hemoglobin as a marker for erythrolysate, we have measured hemoglobin in lymph up to the 10(-6) M range in a number...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.67.5.1097
更新日期:1990-11-01 00:00:00
abstract::Proteases of the plasminogen activator (PA) and matrix metalloproteinase (MMP) system play an important role in smooth muscle cell (SMC) migration and neointima formation after vascular injury. Inhibition of either PAs or MMPs has previously been shown to result in decreased neointima formation in vivo. To inhibit bot...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.0000041418.51906.57
更新日期:2002-11-15 00:00:00
abstract:RATIONALE:Yes-associated protein (YAP), the nuclear effector of Hippo signaling, regulates cellular growth and survival in multiple organs, including the heart, by interacting with TEA (transcriptional enhancer activator)-domain sequence-specific DNA-binding proteins. Recent studies showed that YAP stimulates cardiomyo...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.115.304457
更新日期:2015-01-02 00:00:00
abstract::L-type Ca(2+) channel (LTCC) blockers, represented by amlodipine and verapamil, are widely used antihypertensive drugs that also have antiinflammatory activities. Plasminogen (Plg) is an important mediator of macrophage recruitment, and this role depends on its interaction with Plg receptors (Plg-Rs). Plg-Rs include h...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.109.200311
更新日期:2009-07-17 00:00:00
abstract::Local alterations in the hemodynamic environment regulate endothelial cell function, but the signal-transduction mechanisms involved in this process remain unclear. Because mitogen-activated protein (MAP) kinases have been shown to be activated by physical forces, we measured the phosphorylation and enzyme activity of...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.77.5.869
更新日期:1995-11-01 00:00:00
abstract:RATIONALE:The mutation A341V in the S6 transmembrane segment of KCNQ1, the α-subunit of the slowly activating delayed-rectifier K(+) (I(Ks)) channel, predisposes to a severe long-QT1 syndrome with sympathetic-triggered ventricular tachyarrhythmias and sudden cardiac death. OBJECTIVE:Several genetic risk modifiers have...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.111.249482
更新日期:2012-01-20 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::During ischemia and reperfusion, with an increase in intracellular Na+ and a depolarized membrane potential, Ca2+ may enter the myocyte in exchange for intracellular Na+ via reverse-mode Na+-Ca2+ exchange (NCX). To test the role of Ca2+ entry via NCX during ischemia and reperfusion, we studied mice with cardiac-specif...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000187456.06162.cb
更新日期:2005-10-28 00:00:00
abstract:RATIONALE:Depletion of medial smooth muscle cell (SMC) is a major pathological characteristic of abdominal aortic aneurysm (AAA), although the mechanism by which these cells are eliminated remains incompletely understood. We reasoned that necroptosis, a recently described form of necrosis mediated by receptor-interacti...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.116.304899
更新日期:2015-02-13 00:00:00
abstract::Previous studies have demonstrated a role for voltage-gated K+ (Kv) channel alpha subunits of the Kv4 subfamily in the generation of rapidly inactivating/recovering cardiac transient outward K+ current, I(to,f), channels. Biochemical studies suggest that mouse ventricular I(to,f) channels reflect the heteromeric assem...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000196559.63223.aa
更新日期:2005-12-09 00:00:00
abstract::Although isoform-selective translocation of protein kinase C (PKC) epsilon appears to play an important role in the late phase of ischemic preconditioning (PC), the mechanism(s) responsible for such translocation remains unclear. Furthermore, the signaling pathway that leads to the development of late PC after exogeno...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.84.5.587
更新日期:1999-03-19 00:00:00
abstract::We studied postclamp renal artery pressure and renin release in eight conscious dogs with one-kidney Goldblatt hypertension. On normal sodium intake, intrarenal blockade of angiotensin II with Sar1-Ala8-angiotension II (P-113, saralasin acetate) markedly decreased postclamp renal artery pressure and increased renin re...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.40.3.238
更新日期:1977-03-01 00:00:00