Cardioprotection gain with apelin‐13: A matter of signalling

Lionetti, Vincenzo

doi:10.1111/apha.13005

Cited by 3 publications

(3 citation statements)

References 9 publications

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“…Apelin is a potent regulator of cardiac function and is involved in multiple cardioprotective pathways following toxic insult. − Two key apelin-mediated pathways demonstrated concentration-dependent changes in cardiac gene expression after PH 3 exposure. These concentration-dependent changes suggest that these molecular pathways may play a role in the onset of PH 3 -induced cardiovascular toxicity and potentially in the propagation of PH 3 -induced cardiovascular collapse.…”

Section: Resultsmentioning

confidence: 99%

Transcriptomic Characterization of Inhalation Phosphine Toxicity in Adult Male Sprague–Dawley Rats

Hartog¹,

Lewandowski²,

Hofmann³

et al. 2021

Chem. Res. Toxicol.

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Phosphine (PH 3 ) is a highly toxic, corrosive, flammable, heavier-than-air gas that is a commonly used fumigant. When used as a fumigant, PH 3 can be released from compressed gas tanks or produced from commercially available metal phosphide tablets. Although the mechanism of toxicity is unclear, PH 3 is thought to be a metabolic poison. PH 3 exposure induces multiorgan toxicity, and no effective antidotes or therapeutics have been identified. Current medical treatment consists largely of supportive care and maintenance of cardiovascular function. To better characterize the mechanism(s) driving PH 3 -induced toxicity, we have performed transcriptomic analysis on conscious adult male Sprague−Dawley rats following whole-body inhalation exposure to phosphine gas at various concentration−time products. PH 3 exposure induced concentration-and time-dependent changes in gene expression across multiple tissues. These gene expression changes were mapped to pathophysiological responses using molecular pathway analysis. Toxicity pathways indicative of cardiac dysfunction, cardiac arteriopathy, and cardiac enlargement were identified. These cardiotoxic responses were linked to apelin-mediated cardiomyocyte and cardiac fibroblast signaling pathways. Evaluation of gene expression changes in blood revealed alterations in pathways associated with the uptake, transport, and utilization of iron. Altered erythropoietin signaling was also observed in the blood. Upstream regulator analysis identified several therapeutics predicted to counteract PH 3 -induced gene expression changes. These include antihypertensive drugs (losartan, candesartan, and prazosin) and therapeutics to reduce pathological cardiac remodeling (curcumin and TIMP3). This transcriptomics study has characterized molecular pathways involved in PH 3 -induced cardiotoxicity. These data will aid in elucidating a precise mechanism of toxicity for PH 3 and guide the development of effective medical countermeasures for PH 3 -induced toxicity.

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Section: Resultsmentioning

confidence: 99%

Transcriptomic Characterization of Inhalation Phosphine Toxicity in Adult Male Sprague–Dawley Rats

Hartog¹,

Lewandowski²,

Hofmann³

et al. 2021

Chem. Res. Toxicol.

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“…Indeed, Akt after being phosphorylated by PI3K is able to target mTOR that, in turn, negatively regulates autophagy by inhibiting downstream autophagy-promoting proteins through phosphorylation [ 34 ]. In addition, the Akt/mTOR signalling pathway plays an essential role in protecting the heart [ 35 ]. We thus focused on this pathway, and the obtained results showed that Apelin-13 significantly increased both p-Akt/Akt and p-mTOR/mTOR already after 30 min of treatment.…”

Section: Discussionmentioning

confidence: 99%

Apelin-13 Increases Functional Connexin-43 through Autophagy Inhibition via AKT/mTOR Pathway in the Non-Myocytic Cell Population of the Heart

Vitale

Rosso

Iacono

et al. 2022

IJMS

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Studies have shown a link between the downregulation of connexin 43 (Cx43), the predominant isoform in cardiac gap junctions, and high susceptibility to cardiac arrhythmias and cardiomyocyte death. Non-myocytic cells (NMCs), the most abundant component of the heart, exert multiple cardiac functions and represent an important therapeutic target for diseased cardiac tissue. A few studies have investigated the effect of Apelin-13, an endogenous peptide with a key role in various cardiovascular functions, on Cx43 expression in cardiomyocytes. However, it remained unknown whether Apelin-13 influences Cx43 expression in NMCs. Here, we found that in NMCs, Cx43 protein expression increased after Apelin-13 treatment (100 nM for 48 h). Furthermore, dye transfer assays proved that Apelin-13-treated NMCs had a greater ability to communicate with surrounding cardiomyocytes, and this effect was abrogated by carbenoxolone, a gap junction inhibitor. Interestingly, we showed that Apelin-13 increased Cx43 through autophagy inhibition, as proved by the upregulation of p62 and LC3I, acting as 3-MA, a well-known autophagy inhibitor. In addition, Apelin-13-induced AKT and mTOR phosphorylation was abolished by LY294002 and rapamycin inhibitors resulting in Cx43 increased suppression. These results open the possibility of targeting gap junctions in NMCs with Apelin-13 as an exciting therapeutic approach with great potential.

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“…This article has been published in 2018 in the prestigious journal Acta Physiologica (Oxford) and it has been introduced by an enthusiastic editorial. [21][22][23][24] Research had a most important role in his life and this passion never faded even after retirement. In fact, he continued to show up at the Department of Neuroscience as Professor Emeritus until his conditions allowed so.…”

Section: Journal Of Biological Research 2021; Volume 94:9855mentioning

confidence: 99%

In memory of Professor Gianni Losano. One year after his death

et al. 2021

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Prof. Losano was born on July the 25th 1934, and he graduated in Medicine and Surgery on November 18th 1959. He started his university career in the early 60ties as “Assistente Volontario alla Cattedra di Fisiologia”. He was several times a Visiting Professor at the A.M. Dogliotti College of Medicine of the University of Liberia in Monrovia (Liberia), where he also served as Dean of the Medicine Faculty. In 1973 he was named full professor and he continued to work at Torino University until 2019 as Professor Emeritus.

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Cardioprotection gain with apelin‐13: A matter of signalling

Cited by 3 publications

References 9 publications

Transcriptomic Characterization of Inhalation Phosphine Toxicity in Adult Male Sprague–Dawley Rats

Transcriptomic Characterization of Inhalation Phosphine Toxicity in Adult Male Sprague–Dawley Rats

Apelin-13 Increases Functional Connexin-43 through Autophagy Inhibition via AKT/mTOR Pathway in the Non-Myocytic Cell Population of the Heart

In memory of Professor Gianni Losano. One year after his death

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