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1 tion of EC targets of BMP signaling, such as apelin.
2 echanical stretch and the endogenous peptide apelin.
3 ciated damage, which could not be rescued by apelin.
4 f target genes including APLN, which encodes apelin.
5 equence similarity to the established ligand apelin.
6 abrachial infusions of apelin-36 and (Pyr(1))apelin-13 (0.1 to 30 nmol/min) and subsequently in the p
7 assessed under IV osmotic pump infusions of apelin-13 (0.25 mug/kg/min) or dobutamine (7.5 mug/kg/mi
8 addition, direct microinjection of exogenous apelin-13 (200 pmol in 50 nL) into the RVLM caused a 20
10 infusions of the apelinergic agonists ELA or Apelin-13 (39 and 15 microg/kg/hr, respectively) versus
11 he improved method, we detected pyroglutamyl apelin-13 [(pyr)apelin-13] as the major apelin isoform p
16 del and in both in vivo and ex vivo studies, apelin-13 compared with dobutamine provoked distinctive
17 dilation (p < 0.0001), apelin-36 and (Pyr(1))apelin-13 had no effect on dorsal hand vein diameter (p
18 suggest that the pressor action of [Pyr(1) ]apelin-13 in the RVLM of normotensive rats is not mediat
20 ions of APJ agonism during prolonged (Pyr(1))apelin-13 infusion and renin-angiotensin system activati
22 his inflammatory cardiovascular dysfunction, apelin-13 infusion delivers distinct and optimized hemod
23 f the apelinergic system by exogenous ELA or Apelin-13 infusion improves cardiovascular function and
25 or prolonged systemic (30 nmol/min) (Pyr(1))apelin-13 infusions in the presence or absence of renin-
28 ed luminal secretion of the pyroglutaminated apelin-13 isoform ([Pyr-1]-apelin-13) in the small intes
32 Bilateral RVLM microinjection of [Pyr(1) ]apelin-13 significantly increased ABP (9 +/- 1 mmHg) com
34 Acute cardiac effects of ELA-32 and [Pyr(1)]apelin-13 were assessed by MRI and cardiac catheterizati
38 se beneficial renal effects were superior to Apelin-13, likely because full-length ELA enabled a dist
40 Our study identified new potent analogues of apelin-13, which represent valuable probes to better und
41 y can robustly measure endogenous Ang II and apelin-13-converting activities involved in the renin-an
43 erine residues had no demonstrable impact on apelin-13-induced G protein activation and its intracell
44 e vasopressin V1a receptor but that [Pyr(1) ]apelin-13-induced sympathoexcitation is independent of a
45 etion and angiotensin II coinfusion, (Pyr(1))apelin-13-induced vasodilatation was preserved (P<0.02 f
46 nisms involved in the regulation of [Pyr(1) ]apelin-13-mediated cardiovascular control within the ros
54 od, we detected pyroglutamyl apelin-13 [(pyr)apelin-13] as the major apelin isoform present in plasma
55 previously showed that the C-terminal Phe of apelin 17 (K17F) is crucial for triggering apelin recept
57 ysmography during intrabrachial infusions of apelin-36 and (Pyr(1))apelin-13 (0.1 to 30 nmol/min) and
58 roprusside caused venodilation (p < 0.0001), apelin-36 and (Pyr(1))apelin-13 had no effect on dorsal
59 (30kDa-PEG)] is 10,000-fold less potent than apelin-36 at activating the APJ receptor but retains its
60 e demonstrate that the metabolic activity of apelin-36 can be separated from canonical APJ activation
63 ndings to develop a longer-acting variant of apelin-36 that could modulate glucose homeostasis withou
66 In contrast to its full metabolic activity, apelin-36(L28A) lost the ability to suppress blood press
68 intravenous infusions (0.1 to 3 nmol/min) of apelin-36, (Pyr(1))apelin-13, and sodium nitroprusside (
73 nducible factor stimulates the expression of apelin, a potent vasodilator, in response to reduced blo
75 ystem, adding a conceptual framework for the apelin-ACE2-angiotensin 1-7 axis as a therapeutic target
79 transport of glucose, and 4) intraperitoneal apelin administration in neonates increased glucose upta
81 tives were to establish the effects of acute apelin administration on peripheral, cardiac, and system
84 reased expression of the EC tip cell markers apelin and Dll4 and is associated with a reduction in mi
85 (2015) demonstrate that the secreted protein Apelin and hematopoietic-endothelial cell interactions c
91 the brown adipogenic and browning effects of apelin and suggests a potential therapeutic route to com
92 Taken together, these findings suggest that apelin and/or APJ agonists could potentially be useful a
93 tide), hormonal (e.g., gastrin, ghrelin, and apelin), and paracrine (e.g., histamine) pathways as wel
96 ibits a cardiovascular profile comparable to apelin, and is downregulated in human disease and rodent
97 rgeting of apelin cognate receptor abrogates apelin- and endothelial-mediated expansion of glioblasto
98 FA protein and mRNA for delta-like ligand 4, apelin, angiopoietin-2, and monocyte chemoattractant pro
99 ate the genetic and epigenetic regulation of apelin, apelin receptor (APLNR), and endothelial nitric
102 noncanonical signaling pathway downstream of apelin-APJ involving Galpha13, which induces histone dea
105 Our results demonstrate a novel role for apelin-APJ signaling as a potent regulator of endothelia
108 ommonly shared transcriptional targets among apelin-APJ, Galpha13, and MEF2 in endothelial cells, whi
109 croRNA (miRNA)-dependent association between apelin (APLN) and fibroblast growth factor 2 (FGF2) sign
111 (GPCR) signalling, including that involving apelin (APLN) and its receptor APLNR, is known to be imp
114 nding of the fluoresceinated peptide ligand, APELIN (APLN), or an anti-APLNR mAb, were found in both
115 study and sequencing identified variants of apelin, APLNR, and NOS3 that were validated in a larger
116 schemia, indicative of an important role for apelin/Aplnr in cell recruitment during the nascent biol
118 the identification of the vasoactive peptide apelin as a central regulator for endothelial-mediated m
122 gh having no apparent effect on venous tone, apelin causes nitric oxide-dependent arterial vasodilati
124 Genetic and pharmacological targeting of apelin cognate receptor abrogates apelin- and endothelia
126 measured by immunoassays; however, reported apelin concentrations measured in healthy volunteers sho
128 Taken together, our findings suggest that apelin could be effective in treating PAH by rescuing BM
133 In cell culture experiments, we showed that apelin-deficient PAECs were prone to apoptosis and promo
134 s to be realized due to rapid proteolysis of apelin-derived peptides by proteases, including neprilys
137 and in vivo, protamine abolishes well-known apelin effects, such as angiogenesis, glucose tolerance,
139 energy balance signals such as adiponectin, apelin, endocannabinoids, leptin, insulin and peptide YY
140 n, whereas cardiac precursors overexpressing Apelin exhibited abnormal morphology and rostral migrati
143 Ang-1 also upregulated Jagged-1, Notch3 and apelin expression followed by increases in arteriole for
145 The present study is the first to show that apelin expression is enhanced in the RVLM of SHR versus
147 dy the functional consequence of upregulated apelin expression, apelin was overexpressed by bilateral
148 gged1, Dll4, Hey1, Hey2, Hes1) and decreased apelin expression, suggesting a possible cross-talk betw
149 e RVLM resulted in a significant increase in apelin expression, which was associated with a chronic e
155 ntagonistic relationship between the RAS and apelin has been proposed, such functional interplay rema
157 These findings suggest that in these models apelin has minimal effect on sprouting retinal angiogene
158 logs of the Agtrl1b receptor and its ligand, Apelin, implicated in physiology and angiogenesis, contr
159 iphasic response in autophagy was induced by apelin in AD-MSCs during hypoxia and hypoxia/reoxygenati
160 time, reveals the antioxidant properties of apelin in adipocytes, and suggests its potential as a no
161 activity of this system in rats, the role of apelin in fetal and neonatal glucose homeostasis, and it
164 vivo, the placenta released high amounts of apelin in late gestation, 3) intravenous apelin injectio
166 udy was undertaken to evaluate the effect of apelin in the rostral ventrolateral medulla (RVLM) on bl
172 In rat primary aortic smooth muscle cells, apelin inhibited Ang II-mediated transcriptional regulat
173 ese and insulin-resistant mice treated by an apelin injection (0.1 mumol/kg/day i.p.) during 4 weeks
174 of apelin in late gestation, 3) intravenous apelin injection in mothers increased the transplacental
176 ots demonstrated that microinjection of AAV2-apelin into the RVLM resulted in a significant increase
182 vide both in vitro and in vivo evidence that apelin is able to increase the brown-like characteristic
191 amyl apelin-13 [(pyr)apelin-13] as the major apelin isoform present in plasma from several healthy vo
195 ; however, the central mechanisms underlying apelin-mediated changes in sympathetic nerve activity an
196 sion of an NO synthase inhibitor blocked the apelin-mediated decrease in atherosclerosis and aneurysm
197 In endothelial cells, miR-130/301 modulated apelin-miR-424/503-FGF2 signaling, while in smooth muscl
199 he impaired contractility and hypertrophy of apelin mutant mice, which was accompanied by restored AC
205 dilatation to acetylcholine (P=0.01) but not apelin (P=0.3) or sodium nitroprusside (P=0.9) was atten
208 ELA (ELA), a second endogenous ligand of the Apelin peptide jejunum receptor highly expressed in the
209 ince Apelin-13 signals through its receptor (Apelin peptide jejunum) to exert singular inotropic/vaso
211 the inherent rapid degradation of endogenous apelin peptides and produce metabolically stable small m
212 tivity relationships for chemically modified apelin peptides and recent disclosures of small molecule
217 orts suggest apelin receptor activation with apelin peptides results in cardioprotection as noted thr
218 his study, an optimized method for enriching apelin peptides with cation-exchange beads followed with
219 sis underlying the functional selectivity of apelin peptides, our study indicates that the beta-arres
220 n receptor (Aplnr) and its endogenous ligand apelin play an important role in cardiovascular developm
224 s further supported by the observations that apelin promotes the expression of anti-oxidant enzymes v
227 scovered as a novel endogenous ligand of the apelin receptor (APJ), a G protein-coupled receptor.
228 ce that apelin, through its interaction with apelin receptor (APJ), suppresses production and release
229 hich highlights the importance of inhibiting apelin receptor (APJ); therefore, we developed a cell-ba
232 genetic and epigenetic regulation of apelin, apelin receptor (APLNR), and endothelial nitric oxide sy
234 ed markedly reduced transcripts encoding the apelin receptor (Micu2(-/-) vs. wild type, P = 7.8 x 10(
236 ovides additional proof of principle that an apelin receptor agonist may be of therapeutic use in PAH
238 velopment of metabolically stable ligands of apelin receptor and their effects in various models over
239 , which was blocked by pretreatment with the apelin receptor antagonist, F13A (0 +/- 1 mmHg; P < 0.01
240 the ligand to maintain its affinity for the apelin receptor as well as its capacity to promote apeli
242 f apelin 17 (K17F) is crucial for triggering apelin receptor internalization and decreasing blood pre
243 show that both beta-arrestin recruitment and apelin receptor internalization contribute to the K17F-s
244 agonists with regard to cAMP production and apelin receptor internalization, whereas 21 is a biased
247 r show that during this angioblast migration Apelin receptor signaling is mainly triggered by the rec
248 indicate that Toddler is an activator of APJ/Apelin receptor signaling, promotes gastrulation movemen
251 onally, selective competitive antagonists of apelin receptor were shown to be safe and effective in r
253 tide that acts through the G-protein-coupled apelin receptor, despite lack of sequence similarity to
254 at ELA is an endogenous agonist of the human apelin receptor, exhibits a cardiovascular profile compa
255 of-function mutations in APLNR, encoding the apelin receptor, in patient tumours that were refractory
257 armacology and the physiological role of the apelin receptor, the development of small, bioavailable
259 blasts rely on their intrinsic expression of Apelin receptors (Aplr, APJ) for their migration to the
261 ves internalization of G protein-coupled APJ/Apelin receptors, and activation of APJ/Apelin signaling
264 ersed PAH in mice with reduced production of apelin resulting from deletion of PPARgamma in ECs.
265 tent with these functions, administration of apelin reversed PAH in mice with reduced production of a
266 Among the several studied polymorphisms, apelin rs3761581, rs2235312, and rs3115757; APLNR rs1154
267 cells; we studied whether glucose modulates apelin secretion by enterocytes and the effects of apeli
268 We characterized glucose-related luminal apelin secretion in vivo and ex vivo by mass spectroscop
271 Taken together, these findings indicate that apelin signaling can block Ang II actions in vascular di
273 lmonary arterial hypertension (PAH) in which apelin signaling is downregulated, and to demonstrate at
282 demonstrate that ACE2 couples the RAS to the apelin system, adding a conceptual framework for the ape
285 the present study, we provide evidence that apelin, through its interaction with apelin receptor (AP
287 ll the effects studied were abrogated in HFD apelin-treated mice with muscle-specific inactive AMPK.
290 etween FAO and the tricarboxylic acid cycle, apelin treatment could contribute to insulin sensitivity
292 odepressor function of apelin; we found that apelin treatment increased NO bioavailability in ApoE-KO
297 onsequence of upregulated apelin expression, apelin was overexpressed by bilateral microinjection of
299 implicated in the vasodepressor function of apelin; we found that apelin treatment increased NO bioa
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