Effect of Endothelin on Sodium/Hydrogen Exchanger Activity of Human Monocytes and Atherosclerosis-Related Functions

• Published in: Annals of the New York Academy of Sciences 2007-01, Vol.1095 (1), p.274-291
• Main Authors: KOLIAKOS, GEORGE, BEFANI, CHRISTINA, PALETAS, KONSTANTINOS, KALOYIANNI, MARTHA
• Format: Article
• Language: English
• Subjects: Adult; Atherosclerosis - metabolism; Cation Transport Proteins - metabolism; Endothelin-1 - physiology; Humans; Hydrogen-Ion Concentration; Intracellular Fluid - metabolism; intracellular pH; MAPK; mitogen-activated protein kinase; Monocytes - metabolism; Na+ influx; pHi; phosphatidylinositol 3-kinase; PI3K; PKC; protein kinase C; signaling; Sodium-Hydrogen Exchanger 1; Sodium-Hydrogen Exchangers - metabolism
• ISSN: 0077-8923; 1749-6632
• DOI: 10.1196/annals.1397.031

:  The objective of this article is to investigate the influence of endothelin‐1 (ET‐1) on human monocyte Na+/H+ exchanger (NHE) activity and on the atherosclerosis‐related monocyte functions. ET‐1 caused an increase in pHi and in 22Na influx of monocytes. A reversal of ET‐1 effect on pHi was observed in the presence of the NHE1 inhibitor, cariporide. In addition, the activation of NHE1 by ET‐1 was mediated via protein kinase C (PKC), mitogen‐activated protein kinase (MAPK), phosphatidylinositol 3‐kinase (PI3K), and NADPH oxidase. Also, a link between ET‐1 and nitric oxide (NO) was observed. Furthermore, after ET‐1 treatment, an increase of the adhesive capacity, the migration ability on laminin and CD36 expression of monocytes, was observed; using cariporide this increase was abolished. Our results showed that ET‐1 induces a signaling pathway with the involvement of PKC, MAPK, PI3K, and NADPH oxidase where NHE1 plays a key role. ET‐1 also plays a significant role in atherosclerosis‐related functions of human monocytes, via NHE1 activation.