In vivo genetic profiling and cellular localization of apelin reveals a hypoxia-sensitive, endothelial-centered pathway activated in ischemic heart failure

Sheikh, Ahmad Y.; Chun, Hyung J.; Glassford, Alexander J.; Kundu, Ramendera K.; Kutschka, Ingo; Ardigò, Diego; Hendry, Stephen L.; Wagner, Roger A.; Chen, Mary M; Ali, Ziad A.; Yue, Patrick; Huynh, Diem Thi Ngoc; Connolly, Andrew J.; Pelletier, Marc; Tsao, Philip S.; Robbins, Robert C.; Quertermous, Thomas

doi:10.1152/ajpheart.00935.2007

Cited by 134 publications

(136 citation statements)

References 38 publications

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“…Hypoxia-induced myocardial/endothelial apelin expression has been demonstrated via hypoxia-inducible factor (HIF) pathways (Glassford et al 2007, Ronkainen et al 2007, and the HIF-1 pathway is activated in patients with OSA (Atkeson & Jelic 2008). The pulmonary apelin-producing endothelium is particularly sensitive to hypoxia (Sheikh et al 2008). Thus, upregulation of apelin in OSA may be a protective mechanism against OSA-associated hypertension and recurrent hypoxia/hypoxaemia, and endothelial dysfunction may represent the dominant mechanism for circulating plasma apelin levels in this patient group.…”

Section: Discussionmentioning

confidence: 98%

Plasma apelin levels in obstructive sleep apnea and the effect of continuous positive airway pressure therapy

Henley¹,

Buchanan²,

Gibson³

et al. 2009

Journal of Endocrinology

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Apelin is a peptide hormone with cardiovascular and glucose homeostasis properties, and obstructive sleep apnea (OSA) is complicated by cardiovascular and metabolic comorbidities. Plasma apelin has not been previously assessed in OSA. We investigated the response of plasma apelin to a 2-h 75 g oral glucose tolerance test (OGTT) and the effect of 3 months compliant continuous positive airway pressure (CPAP) therapy in 15 obese males with newly diagnosed OSA. Plasma apelin and serum cortisol were recorded 10 minutely, while serum insulin and glucose were measured 30 minutely. Ten subjects had plasma apelin measured at intervals across a 24-h period to investigate for circadian variation in apelin levels, and this was repeated following 3 months compliant CPAP therapy. Fasting (0 . 342G0 . 038 vs 0 . 288 G0 . 024 ng/ml, PZ0 . 04), 30 min (0 . 399G0 . 035 vs 0 . 312 G0 . 036 ng/ml, PZ0 . 007) and 120 min (0 . 402G0 . 030 vs 0 . 259G0 . 024 ng/ml, P!0 . 001) apelin levels were reduced following CPAP. The area under curve for apelin OGTT response was lower post-CPAP (44 . 1G3 . 3 vs 35 . 8 G2 . 3 ng/ml per min, P!0 . 001). Mean OGTT apelin levels showed a significant treatment effect (PZ0 . 006) and a time effect (P!0 . 001), and the effect of time was different preversus post-CPAP (PZ0 . 005). No significant variability in apelin levels existed across the 24-h period at diagnosis. Lower levels were evident overnight following treatment (PZ0 . 004). Improvements in insulin and glucose parameters and reduced cortisol levels were found post-CPAP. In summary, untreated OSA was associated with elevated plasma apelin levels, altered apelin secretory dynamics in response to oral glucose and lack of an apparent circadian variability, which was restored following CPAP.

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Section: Discussionmentioning

confidence: 98%

Plasma apelin levels in obstructive sleep apnea and the effect of continuous positive airway pressure therapy

Henley¹,

Buchanan²,

Gibson³

et al. 2009

Journal of Endocrinology

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“…Unfortunately, for most of the HKG used in published results, no exhaustive studies of their variations in dedicated conditions have been performed yet. For example, a lot of reports deal with transcripts variation under hypoxia (Helczynska et al, 2008;Seifeddine et al, 2008;Sheikh et al, 2008;Chaudary and Hill, 2009;Zhang et al, 2009). Authors formulate relevant conclusions regarding gene expression on the basis of the use in most cases of a unique or more rarely a specific set of HKG.…”

Section: Discussionmentioning

confidence: 99%

“…Many publications dealing with cancer have reported gene expression studies in hypoxic conditions (Helczynska et al, 2008;Seifeddine et al, 2008;Sheikh et al, 2008;Chaudary and Hill, 2009;Zhang et al, 2009), but until now related HKG variations have not yet been much characterised (Zhong and Simons, 1999). However, analysing if HKG expression is stable under different oxygen concentrations remains an important issue especially in cancer field as it is well known that proliferating tumours often grow in hypoxic conditions (Semenza, 2003).…”

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confidence: 99%

‘Desperate house genes’: the dramatic example of hypoxia

Caradec

Sirab

Keumeugni³

et al. 2010

Br J Cancer

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BACKGROUND: Microenvironmental conditions in normal or tumour tissues and cell lines may interfere on further biological analysis. To evaluate transcript variations carefully, it is common to use stable housekeeping genes (HKG) to normalise quantitative microarrays or real-time polymerase chain reaction results. However, recent studies argue that HKG fluctuate according to tissues and treatments. So, as an example of HKG variation under an array of conditions that are common in the cancer field, we evaluate whether hypoxia could have an impact on HKG expression. METHODS: Expression of 10 commonly used HKG was measured on four cell lines treated with four oxygen concentrations (from 1 to 20%). RESULTS: Large variations of HKG transcripts were observed in hypoxic conditions and differ along with the cell line and the oxygen concentration. To elect the most stable HKG, we compared the three statistical means based either on PCR cycle threshold coefficient of variation calculation or two specifically dedicated software. Nevertheless, the best HKG dramatically differs according to the statistical method used. Moreover, using, as a reference, absolute quantification of a target gene (here the proteinase activating receptor gene 1 (PAR1) gene), we show that the conclusions raised about PAR1 variation in hypoxia can totally diverge according to the selected HKG used for normalisation. CONCLUSION: The choice of a valid HKG will determine the relevance of the results that will be further interpreted, and so it should be seriously considered. The results of our study confirm unambiguously that HKG variations must be precisely and systematically determined before any experiment for each situation, to obtain reliable normalised results in the experimental setting that has been designed. Indeed, such assay design, functional for all in vitro systems, should be carefully evaluated before any extension to other experimental models including in vivo ones.

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“…However, studying the racemic status 23 was the determinant for decreased plasma apelin content among heart involvement. In contrast, the recent studies reported by Sheikh and associates 24 demonstrated that apelin and APJ were up-regulated in the heart and skeletal muscle after myocardial injury, suggesting that apelin expression remains in the endothelium.…”

Section: Discussionmentioning

confidence: 61%

“…Studies suggest that apelin-expressing endothelial cells respond in conditions associated with heart failure, possibly including local tissue hypoxia, thereby modulating apelin-APJ expression to regulate cardiovascular homeostasis, the apelin-APJ pathway may thus provide a mechanism for systemic endothelial monitoring of tissue perfusion and adaptive regulation of cardiovascular function. 24 Because apelin improves glucose uptake and mediates the inflammatory response, apelin may be a promising therapeutic agent for type 2 diabetes. However, further studies that investigate the protein and mRNA levels of the anti-insulin resistant effect of apelin, and in vivo studies of apelin in insulinresistant animals are necessary to elucidate its pharmaceutical potential.…”

Section: Discussionmentioning

confidence: 99%

Untitled

2015

Exp Clin Transplant

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Objectives: Apelin, a cytokine mainly secreted by adipocytes and several tissues, includes the gastrointestinal tract, adipose, brain, kidney, liver, lung, and various sites within the cardiovascular system. Apelin is closely related to glucose metabolism, and has been proposed to be a promising therapeutic agent in treating insulin resistance. Apelin and orphaned G-protein-coupled apelin exhibit roles in regulating fluid homeostasis. Circulating serum apelin suppresses insulin secretion by binding to the G-protein-coupled apelin receptor on B cells of islets of Langerhans. Several studies also have documented the altered level of serum apelin in type 2 diabetic patients, but the results remain controversial. This study sought to analyze apelin levels in new-onset diabetes after transplant. Materials and Methods: Forty-seven diabetic renal transplant recipients were compared with 40 nondiabetic renal transplant recipients. Data were collected for positive family history of diabetes, body weight, body mass index, blood pressure, and blood chemistry including apelin level. Logistic multiple analysis were made for statistically significant data on univariate analysis. Results: Apelin levels were significantly higher among obese, hypercholesterolemia new-onset diabetes after transplant patients, 428.7 ± 193.29, 256.8 ± 128 (P > .001). There was appositive correlation between serum apelin and proteinuria. Conclusions: Serum apelin has a high level in newonset diabetes after transplant, than nondiabetic patients, and they positively correlate with proteuria in new-onset diabetes after transplant patients.

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In vivo genetic profiling and cellular localization of apelin reveals a hypoxia-sensitive, endothelial-centered pathway activated in ischemic heart failure

Cited by 134 publications

References 38 publications

Plasma apelin levels in obstructive sleep apnea and the effect of continuous positive airway pressure therapy

Plasma apelin levels in obstructive sleep apnea and the effect of continuous positive airway pressure therapy

‘Desperate house genes’: the dramatic example of hypoxia

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