Monomeric adiponectin modulates nitric oxide release and calcium movements in porcine aortic endothelial cells in normal/high glucose conditions

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• 作者：Elena Grossini^a ; ^{Elena.grossini@med.uniupo.it" class="auth_mail" title="E-mail the corresponding author} ; Serena Farruggio^a ; Fatima Qoqaiche^a ; Giulia Raina^a ; Lara Camillo^a ; Lorenzo Sigaudo^a ; David Mary^a ; Nicola Surico^b ; Daniela Surico^b
• 关键词：ACh ; acetylcholine ; AdipoR ; adiponectin receptor ; AMPK ; 5&prime ; adenosine monophosphate-activated protein kinase ; CAMKII ; Ca2  ; + calmodulin kinase II ; DMEM ; Dulbecco's modified Eagle's medium ; EGTA ; ethylene glycol tetraacetic acid ; eNOS ; endothelial nitric oxide synthase ; ERK1/2 ; extracellular-signal-regulated kinases ; FURA-2/AM ; Fura-2/acetoxymethyl ester ; L-NAME ; Nω-nitro-l-arginine methyl ester ; MAPK ; mitogen-activated protein kinase ; NCX ; Na+/ Ca2  ; + exchanger ; NO ; nitric oxide ; NO
• 刊名：Life Sciences
• 出版年：2016
• 出版时间：15 September 2016
• 年：2016
• 卷：161
• 期：Complete
• 页码：1-9
• 全文大小：951 K

文摘

Perivascular adipose tissue can be involved in the process of cardiovascular pathology through the release of adipokines, namely adiponectins. Monomeric adiponectin has been shown to increase coronary blood flow in anesthetized pigs through increased nitric oxide (NO) release and the involvement of adiponectin receptor 1 (AdipoR1). The present study was therefore planned to examine the effects of monomeric adiponectin on NO release and Ca^2 + transients in porcine aortic endothelial cells (PAEs) in normal/high glucose conditions and the related mechanisms.

Main methods

PAEs were treated with monomeric adiponectin alone or in the presence of intracellular kinases blocker, AdipoR1 and Ca^2 +-ATPase pump inhibitors. The role of Na⁺/Ca^2 + exchanger was examined in experiments performed in zero Na⁺ medium. NO release and intracellular Ca^2 + were measured through specific probes.

Key findings

In PAE cultured in normal glucose conditions, monomeric adiponectin elevated NO production and [Ca^2 +]c. Similar effects were observed in high glucose conditions, although the response was lower and not transient. The Ca^2 + mobilized by monomeric adiponectin originated from an intracellular pool thapsigargin- and ATP-sensitive and from the extracellular space. Moreover, the effects of monomeric adiponectin were prevented by kinase blockers and AdipoR1 inhibitor. Finally, in normal glucose condition, a role for Na⁺/Ca^2 + exchanger and Ca^2 +-ATPase pump in restoring Ca^2 + was found.

Significance

Our results add new information about the control of endothelial function elicited by monomeric adiponectin, which would be achieved by modulation of NO release and Ca^2 + transients. A signalling related to Akt, ERK1/2 and p38MAPK downstream AdipoR1 would be involved.