Grossini Elena, Farruggio Serena, Qoqaiche Fatima, Raina Giulia, Camillo Lara, Sigaudo Lorenzo, Mary David, Surico Nicola, Surico Daniela
Lab. Physiology/Experimental Surgery, Dept. of Translational Medicine, University Eastern Piedmont "A. Avogadro", Azienda Ospedaliera Universitaria Maggiore della Carità, Corso Mazzini 36, Novara, Via Solaroli 17, Italy.
Lab. Physiology/Experimental Surgery, Dept. of Translational Medicine, University Eastern Piedmont "A. Avogadro", Azienda Ospedaliera Universitaria Maggiore della Carità, Corso Mazzini 36, Novara, Via Solaroli 17, Italy.
Life Sci. 2016 Sep 15;161:1-9. doi: 10.1016/j.lfs.2016.07.010. Epub 2016 Jul 26.
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.
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.
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.
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.
血管周围脂肪组织可通过释放脂肪因子（即脂联素）参与心血管病理过程。已表明单体脂联素可通过增加一氧化氮（NO）释放和脂联素受体1（AdipoR1）的参与来增加麻醉猪的冠状动脉血流量。因此，本研究旨在检测单体脂联素在正常/高糖条件下对猪主动脉内皮细胞（PAEs）中NO释放和Ca(2+)瞬变的影响及其相关机制。
PAEs单独用单体脂联素处理，或在存在细胞内激酶阻滞剂、AdipoR1和Ca(2+)-ATP酶泵抑制剂的情况下处理。在零钠培养基中进行的实验中检测钠/钙交换器的作用。通过特异性探针测量NO释放和细胞内Ca(2+)。
在正常葡萄糖条件下培养的PAE中，单体脂联素提高了NO生成和[Ca(2+)]c。在高糖条件下也观察到类似的效果，尽管反应较低且不是瞬时的。单体脂联素动员的Ca(2+)来源于毒胡萝卜素和ATP敏感的细胞内池以及细胞外空间。此外，激酶阻滞剂和AdipoR1抑制剂可阻止单体脂联素的作用。最后，在正常葡萄糖条件下，发现钠/钙交换器和Ca(2+)-ATP酶泵在恢复Ca(2+)方面的作用。
我们的结果为单体脂联素引发的内皮功能控制增加了新信息，这将通过调节NO释放和Ca(2+)瞬变来实现。将涉及与AdipoR1下游的Akt、ERK1/2和p38MAPK相关的信号传导。
