Pulmonary apelin levels and effects in rats with hypoxic pulmonary hypertension

Andersen, Charlotte Uggerhøj; Markvardsen, Lars Kjøbsted; Hilberg, Ole; Simonsen, Ulf

doi:10.1016/j.rmed.2009.05.011

Cited by 45 publications

(49 citation statements)

References 30 publications

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“…The AP13 effect was maintained on pulmonary vessels from OSR, but not from PHR. These results are in agreement with those obtained by Andersen and colleagues [23] and could be the result of reduced AP13 effects on vessels with endothelial malfunction.…”

Section: Discussionsupporting

confidence: 93%

“…For this study, 10 nM AP13 was added to the organ bath, on basal tone, with 15 minutes before Phe. At this concentration, AP13 did not significantly modify the vasoconstrictor agents on rat pulmonary arteries [23,36] but, as we demonstrated, could increase the LEP-induced vasodilatation on NR by an average of more than 40%. The dramatic decrease of AP13 effects in the presence of 0.1 mM L-NAME (Figure 1) suggests a large dependence on NO synthesis.…”

Section: Discussionmentioning

confidence: 59%

“…Therefore, our data agreed with published results. In addition, the LEP vasodilatatory effects are significantly lower in OSR ( Figure 3) and almost ceased in PHR (Figure 4), a possible result of vascular distress produced by bronchial allergic disease [36] or by hypertension [23].…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies showed that AP13 could induce both endothelium-dependent and NO-mediated transient relaxations of pulmonary artery rings, and that it attenuated the response to vasoconstrictors [22,23].…”

Section: Vascular Tonementioning

confidence: 99%

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Synergistic effects of apelin and leptin on isolated rat pulmonary arteries

et al. 2011

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AbstractApelin (AP) and leptin (LEP) are adipokines with vasomotor actions. Taking into account the published data on the role of obesity in the development of pulmonary hypertension, we studied the implications of apelin on leptin relaxing effects on isolated rat pulmonary arteries. LEP had vasodilatatory effects on phenylephrine-precontracted rat pulmonary arteries from normal and ovalbumin-sensitized rats, but not on rats with monocrotaline-induced pulmonary hypertension. AP13 pretreatment increased LEP effects by one-half. Our studies revealed the existence of synergistic favorable effects of these adipokines on pulmonary vessels.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 59%

Section: Discussionmentioning

confidence: 99%

Section: Vascular Tonementioning

confidence: 99%

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Synergistic effects of apelin and leptin on isolated rat pulmonary arteries

et al. 2011

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“…Taken together, our findings support a concept where the endothelial PHD2/HIF-2 axis blunts APLN-mediated vasodilatory effects by inhibiting Aplnr expression and by limiting HIF-1-dependent induction of Apln. Consistent with this model are previous studies in which APLN-mediated effects on vascular tone were lost under hypoxic conditions (54). Furthermore, two genetic APLNR variants (rs11544374 and rs2282623) were associated with a predisposition to high-altitude pulmonary edema, reinforcing the concept that APLNR signaling plays a critical role in hypoxia-induced vascular responses in the lungs (55).…”

Section: Hif2supporting

confidence: 84%

The Endothelial Prolyl-4-Hydroxylase Domain 2/Hypoxia-Inducible Factor 2 Axis Regulates Pulmonary Artery Pressure in Mice

Kapitsinou

Rajendran

Astleford

et al. 2016

Molecular and Cellular Biology

115

138

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f Hypoxia-inducible factors 1 and 2 (HIF-1 and -2) control oxygen supply to tissues by regulating erythropoiesis, angiogenesis and vascular homeostasis. HIFs are regulated in response to oxygen availability by prolyl-4-hydroxylase domain (PHD) proteins, with PHD2 being the main oxygen sensor that controls HIF activity under normoxia. In this study, we used a genetic approach to investigate the endothelial PHD2/HIF axis in the regulation of vascular function. We found that inactivation of Phd2 in endothelial cells specifically resulted in severe pulmonary hypertension (ϳ118% increase in right ventricular systolic pressure) but not polycythemia and was associated with abnormal muscularization of peripheral pulmonary arteries and right ventricular hypertrophy. Concurrent inactivation of either Hif1a or Hif2a in endothelial cell-specific Phd2 mutants demonstrated that the development of pulmonary hypertension was dependent on HIF-2␣ but not HIF-1␣. Furthermore, endothelial HIF-2␣ was required for the development of increased pulmonary artery pressures in a model of pulmonary hypertension induced by chronic hypoxia. We propose that these HIF-2-dependent effects are partially due to increased expression of vasoconstrictor molecule endothelin 1 and a concomitant decrease in vasodilatory apelin receptor signaling. Taken together, our data identify endothelial HIF-2 as a key transcription factor in the pathogenesis of pulmonary hypertension.

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Orthogonal Peptide‐Templated Labeling Elucidates Lateral ET_AR/ET_BR Proximity and Reveals Altered Downstream Signaling

et al. 2021

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Fine-tuning of G protein-coupled receptor (GPCR) signaling is important to maintain cellular homeostasis. Recent studies demonstrated that lateral GPCR interactions in the cell membrane can impact signaling profiles. Here, we report on a onestep labeling method of multiple membrane-embedded GPCRs. Based on short peptide tags, complementary probes transfer the cargo (e. g. a fluorescent dye) by an acyl transfer reaction with high spatial and temporal resolution within 5 min. We applied this approach to four receptors of the cardiovascular system: the endothelin receptor A and B (ET A R and ET B R), angiotensin II receptor type 1, and apelin. Wild type-like G protein activation after N-terminal modification was demonstrated for all receptor species. Using FRET-competent dyes, a constitutive proximity between hetero-receptors was limited to ET A R/ET B R. Further, we demonstrate, that ET A R expression regulates the signaling of co-expressed ET B R. Our orthogonal peptide-templated labeling of different GPCRs provides novel insight into the regulation of GPCR signaling.

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Pulmonary apelin levels and effects in rats with hypoxic pulmonary hypertension

Cited by 45 publications

References 30 publications

Synergistic effects of apelin and leptin on isolated rat pulmonary arteries

Synergistic effects of apelin and leptin on isolated rat pulmonary arteries

The Endothelial Prolyl-4-Hydroxylase Domain 2/Hypoxia-Inducible Factor 2 Axis Regulates Pulmonary Artery Pressure in Mice

Orthogonal Peptide‐Templated Labeling Elucidates Lateral ET_AR/ET_BR Proximity and Reveals Altered Downstream Signaling

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Pulmonary apelin levels and effects in rats with hypoxic pulmonary hypertension

Cited by 45 publications

References 30 publications

Synergistic effects of apelin and leptin on isolated rat pulmonary arteries

Synergistic effects of apelin and leptin on isolated rat pulmonary arteries

The Endothelial Prolyl-4-Hydroxylase Domain 2/Hypoxia-Inducible Factor 2 Axis Regulates Pulmonary Artery Pressure in Mice

Orthogonal Peptide‐Templated Labeling Elucidates Lateral ETAR/ETBR Proximity and Reveals Altered Downstream Signaling

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Orthogonal Peptide‐Templated Labeling Elucidates Lateral ET_AR/ET_BR Proximity and Reveals Altered Downstream Signaling