Apelin decreases myocardial injury and improves right ventricular function in monocrotaline-induced pulmonary hypertension

Falcão-Pires, Inês; Gonçalves, Nádia; Henriques‐Coelho, Tiago; Moreira-Gonçalves, Daniel; Roncon‐Albuquerque, Roberto; Leite‐Moreira, Adelino F.

doi:10.1152/ajpheart.00089.2009

Cited by 131 publications

(108 citation statements)

References 43 publications

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“…With the criteria used, we may have excluded a large number of gene targets of the PPARγ/β-catenin complex. Although we identified a number of genes related to EC homeostasis, we focused on APLN among the 18 targets, both because it was among the most highly regulated and because its reduction, like that of BMPR2, was linked to clinical PAH (28).…”

Section: Discussionmentioning

confidence: 99%

“…Of the genes identified, APLN has been linked to both experimental models and clinical examples of PAH. Circulating ape- lin levels are decreased in IPAH patients (27), and apelin administration improves RV function in the monocrotaline rat model of PAH (28). In addition, loss of apelin worsens hypoxia-induced pulmonary hypertension in association with decreased number and enhanced muscularization of peripheral arteries (29).…”

Section: Figurementioning

confidence: 99%

“…Moreover, it represents the replacement of a key downstream gene that is lost when there is dysfunctional BMPR2 signaling. This, coupled with its properties as a vasodilator and as a potent activator of LV and RV contractility (28,51), makes apelin a very attractive therapeutic target for treating PAH.…”

Section: Figurementioning

confidence: 99%

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Disruption of PPARγ/β-catenin–mediated regulation of apelin impairs BMP-induced mouse and human pulmonary arterial EC survival

Alastalo¹,

Li²,

Perez³

et al. 2011

J. Clin. Invest.

225

298

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Reduced bone morphogenetic protein receptor 2 (BMPR2) expression in patients with pulmonary arterial hypertension (PAH) can impair pulmonary arterial EC (PAEC) function. This can adversely affect EC survival and promote SMC proliferation. We hypothesized that interventions to normalize expression of genes that are targets of BMPR2 signaling could restore PAEC function and prevent or reverse PAH. Here we have characterized, in human PAECs, a BMPR2-mediated transcriptional complex between PPARγ and β-catenin and shown that disruption of this complex impaired BMP-mediated PAEC survival. Using whole genome-wide ChIP-Chip promoter analysis and gene expression microarrays, we delineated PPARγ/β-catenin-dependent transcription of target genes including APLN, which encodes apelin. We documented reduced PAEC expression of apelin in PAH patients versus controls. In cell culture experiments, we showed that apelin-deficient PAECs were prone to apoptosis and promoted pulmonary arterial SMC (PASMC) proliferation. Conversely, we established that apelin, like BMPR2 ligands, suppressed proliferation and induced apoptosis of PASMCs. Consistent with these functions, administration of apelin reversed PAH in mice with reduced production of apelin resulting from deletion of PPARγ in ECs. Taken together, our findings suggest that apelin could be effective in treating PAH by rescuing BMPR2 and PAEC dysfunction.

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Section: Discussionmentioning

confidence: 99%

Section: Figurementioning

confidence: 99%

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Disruption of PPARγ/β-catenin–mediated regulation of apelin impairs BMP-induced mouse and human pulmonary arterial EC survival

Alastalo¹,

Li²,

Perez³

et al. 2011

J. Clin. Invest.

225

298

View full text Add to dashboard Cite

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“…In the control groups, the same volume of serum physiologic was injected. The rats of C+A and HT+A groups were treated with pyroglutamylated apelin-13 (Pyr-AP13; 200 μg.kg -1 .day -1 ip) during 17 days (26). Apelin administration initiated in HT+A group after than hypertension developed.…”

Section: Hypertension Modelingmentioning

confidence: 99%

Supplementation of apelin increase plasma levels of nesfatin-1 in normal and DOCA-salt hypertensive rats

Akçılar¹,

Ayada²,

Turgut³

et al. 2015

BLL

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Aims:We aimed to observe the effects of apelin supplementation on the plasma levels of nesfatin-1 in DOCA-salt hypertensive and normal rats. Methods: For this purpose, 28 young Wistar albino male rats were divided into four groups; Control (C), Control + Apelin (C+A), Hypertension (HT) and Hypertension + Apelin (HT+A). Hypertension was induced by injection of DOCA-salt (25 mg/kg, s.c.) twice weekly, 4 weeks, whereas intraperitoneal apelin was administered (200 μg.kg -1 ) for 17 days. Plasma nesfatin-1 and apelin levels were measured with ELISA. Systolic blood pressure was monitored using a tail cuff system. The relationships between plasma nesfatin levels and blood pressure were assessed. Results: Plasma nesfatin-1 levels was found lower in control animals compared to C+A, HT and HT+A groups (p = 0.002, p = 0.026 and p = 0.011, respectively). Systolic blood pressures were similar in the C and C+A groups, but systolic blood pressures of the HT and HT+A groups was found signifi cantly higher than the C and C+A groups. Conclusions: In conclusion, apelin administration induced an increment of nesfatin-1 in normal rats and plasma levels of nesfatin-1 increase in DOCA-salt hypertension rats. But apelin addition in hypertension did not cause an extra increase in nesfatin-1 levels. This is the fi rst report to investigate the effect of apelin administration on plasma nesfatin levels of normal and hypertensive rats (Fig. 2, Ref. 44). Text in PDF www.elis.sk.

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“…Therefore, we used Pyr-AP13 for this chronic study. 19 Age-matched male DR rats served as a control group (DR-C).…”

Section: Animal Models and Experimental Designsmentioning

confidence: 99%

Cardioprotective Effect of Apelin-13 on Cardiac Performance and Remodeling in End-Stage Heart Failure

Koguchi

Kobayashi

Takeshima

et al. 2012

Circ J

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Apelin decreases myocardial injury and improves right ventricular function in monocrotaline-induced pulmonary hypertension

Cited by 131 publications

References 43 publications

Disruption of PPARγ/β-catenin–mediated regulation of apelin impairs BMP-induced mouse and human pulmonary arterial EC survival

Disruption of PPARγ/β-catenin–mediated regulation of apelin impairs BMP-induced mouse and human pulmonary arterial EC survival

Supplementation of apelin increase plasma levels of nesfatin-1 in normal and DOCA-salt hypertensive rats

Cardioprotective Effect of Apelin-13 on Cardiac Performance and Remodeling in End-Stage Heart Failure

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