Targeting the apelin system for the treatment of cardiovascular diseases

Chapman, Fiona A; Maguire, Janet J; Newby, David E; Davenport, Anthony P; Dhaun, Neeraj

doi:10.1093/cvr/cvad171

Cited by 8 publications

(2 citation statements)

References 179 publications

(250 reference statements)

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“…The apelin system (apelin and its receptor) is currently being investigated as a possible treatment target for CKD and its associated cardiovascular diseases ( ClinicalTrials.gov : NCT03956576) as it counteracts the renin-angiotensin-aldosterone system (RAAS), reduces blood pressure, and has an anti-inflammatory and antifibrotic effect [ 10 , 42 ]. Whether an apelin agonist could offer additional benefits to current renoprotective treatments such as RAAS- and SGLT2-inhibitiors would be of great interest.…”

Section: Discussionmentioning

confidence: 99%

Apelin and Copeptin Levels in Patients With Chronic SIAD Treated With Empagliflozin

Monnerat,

Drivakos,

Chapman

et al. 2024

Journal of the Endocrine Society

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Background Empagliflozin increases sodium levels in patients with a chronic syndrome of inappropriate antidiuresis (SIAD) and dapagliflozin increases apelin levels in patients with diabetes mellitus. Exogenous apelin increases sodium levels in rats with SIAD. We aimed to investigate whether an increase in plasma apelin concentration may contribute to the efficacy of empagliflozin in SIAD. Methods Post-hoc secondary analysis of a double-blind, crossover, placebo-controlled trial performed from 12/2017 to 08/2021 at the University Hospital Basel, Switzerland, investigating the effect of 4 weeks treatment with empagliflozin 25 mg/day as compared to placebo in 14 outpatients with chronic SIAD (NCT03202667). The objective was to investigate the effect of empagliflozin on plasma apelin and copeptin concentrations and their ratio. Results Fourteen patients, 50% female, with a median [IQR] age of 72 years [65–77] were analyzed. Median apelin concentration was 956 pmol/l [853, 1038] at baseline. Median [IQR] apelin relative changes were +11% [0.7, 21] and +8% [-5, 25] (P = 0.672) at the end of the placebo and empagliflozin phases, respectively. Median copeptin concentration was 2.6 [2.2, 4.5] pmol/l at baseline and had a relative change of +5 [-2. 11]% and +25% [10, 28] (P = 0.047) over the placebo and empagliflozin phases, respectively. Conclusions Empagliflozin did not lead to significant changes in apelin or the apelin/copeptin ratio in patients with chronic SIAD, but led to an increase in copeptin. This suggests that the efficacy of empagliflozin in SIAD is independent of apelin and is not blunted by the adaptative increase in copeptin.

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Section: Discussionmentioning

confidence: 99%

Apelin and Copeptin Levels in Patients With Chronic SIAD Treated With Empagliflozin

Monnerat,

Drivakos,

Chapman

et al. 2024

Journal of the Endocrine Society

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“…Central sources of apelin, such as from magnocellular neurons, also contribute to circulating Apelins. Apelins act in an autocrine/paracrine manner ( 10 ). In the context of regulating glucose levels, the role of Apelin-13, which is a critical regulator of lipid metabolism, has assumed significance.…”

Section: Introductionmentioning

confidence: 99%

Apelin‑13 reduces high glucose‑induced mitochondrial dysfunction in cochlear hair cells by inhibiting endoplasmic reticulum stress

Huo,

Gu,

2024

Exp Ther Med

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The complex manifestation of diabetic hearing loss and the relative inaccessibility of the inner ear contribute to the lack of research. The present study aimed to reveal the role of Apelin-13, a critical regulator of lipid metabolism, in diabetes-induced hearing loss. Cochlear hair cells treated with high glucose (HG) were adopted as an in vitro research model, and the impacts of Apelin-13 on cellular oxidative stress, apoptosis, mitochondrial dysfunction and endoplasmic reticulum (ER) stress were determined. In addition, cells were treated with the ER stress agonist tunicamycin to further explore its potential role in the regulatory effects of Apelin-13. Apelin-13 inhibited oxidative stress and apoptosis in the HG-induced cells. Additionally, Apelin-13 elevated mitochondrial membrane potential and ATP production, whereas it reduced mitochondrial reactive oxygen species levels. The levels of ER stress-related proteins exhibited a downward trend in response to Apelin-13. By contrast, tunicamycin reversed the effects of Apelin-13 on the aforementioned aspects, suggesting the role of ER stress in the regulatory effects of Apelin-13. In conclusion, the present study elucidated the protective role of Apelin-13 in ameliorating HG-induced mitochondrial functional impairment in cochlear hair cells by inhibiting ER stress.

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The maternal lifestyle in pregnancy: Implications for foetal skeletal muscle development

Sun,

Chen,

Liao

et al. 2024

J cachexia sarcopenia muscle

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The world is facing a global nutrition crisis, as evidenced by the rising incidence of metabolic disorders such as obesity, insulin resistance and chronic inflammation. Skeletal muscle is the largest tissue in humans and plays an important role in movement and host metabolism. Muscle fibre formation occurs mainly during the embryonic stage. Therefore, maternal lifestyle, especially nutrition and exercise during pregnancy, has a critical influence on foetal skeletal muscle development and the subsequent metabolic health of the offspring. In this review, the influence of maternal obesity, malnutrition and micronutrient intake on foetal skeletal muscle development is systematically summarized. We also aim to describe how maternal exercise shapes foetal muscle development and metabolic health in the offspring. The role of maternal gut microbiota and its metabolites on foetal muscle development is further discussed, although this field is still in its ‘infancy’. This review will provide new insights to reduce the global crisis of metabolic disorders and highlight current gaps to promote further research.

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Targeting the apelin system for the treatment of cardiovascular diseases

Cited by 8 publications

References 179 publications

Apelin and Copeptin Levels in Patients With Chronic SIAD Treated With Empagliflozin

Apelin and Copeptin Levels in Patients With Chronic SIAD Treated With Empagliflozin

Apelin‑13 reduces high glucose‑induced mitochondrial dysfunction in cochlear hair cells by inhibiting endoplasmic reticulum stress

The maternal lifestyle in pregnancy: Implications for foetal skeletal muscle development

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