Apelin suppresses apoptosis of human vascular smooth muscle cells via APJ/PI3-K/Akt signaling pathways

Abstract

Apoptosis of vascular smooth muscle cells (VSMCs) plays an important role in regulating vascular remodeling during cardiovascular diseases. Apelin is the endogenous ligand for the G-protein-coupled receptor APJ and plays an important role in the cardiovascular system. However, the mechanisms of apelin on apoptosis of VSMCs have not been elucidated. Using a culture of human VSMCs as a model for the study of apoptosis, the relationship between apelin and apoptosis of human VSMCs and the signal pathway involved were investigated. Using western blotting, we confirmed that VSMCs could express APJ. To evaluate the possible role of apelin in VSMC apoptosis, we assessed its effect on apoptosis of human VSMCs. The results showed that apelin inhibited human VSMCs apoptosis induced by serum deprivation. Suppression of APJ with small-interfering RNA (siRNA) abolished the anti-apoptotic activity of apelin. Apelin increased Bcl-2 protein expression, but decreased Bax protein expression. An increase in activation of extracellular signal-regulated protein kinase (ERK) and Akt (a downstream effector of phosphatidylinositol 3-kinase) was shown after apelin stimulation. Suppression of APJ with siRNA abolished the apelin-induced activation of ERK and Akt. LY294002 (a PI3-K inhibitor) blocked apelin-induced activation of Akt and abolished the apelin-induced antiapoptotic activity. Our study suggests that apelin suppresses serum deprivation-induced apoptosis of human VSMCs, and that the anti-apoptotic action is mediated through the APJ/PI3-K/Akt signaling pathways.

The apelin receptor APJ: journey from an orphan to a multifaceted regulator of homeostasis

“…Additionally, apelin activates Akt in rat hippocampal neuronal cultures, suggesting a neuroprotective role (O'Donnell et al 2007), while in mouse cortical neurones, the neuroprotective action of apelin is blocked by the PI3K inhibitor wortmannin, implicating the PI3K/Akt pathway in this process (Zeng et al 2010). APJ signalling via PI3K/Akt is also involved in proliferation and anti-apoptotic actions in rat and human VSMCs respectively (Cui et al 2010, Liu et al 2010. Studies carried out in vivo have shown the involvement of apelin in cardioprotection via Aktmediated signalling ); however, the protective effect of apelin in ischaemia/reperfusion may be independent of Akt signalling (Kleinz & Baxter 2008).…”

Effect of apelin on mitosis, apoptosis and DNA repair enzyme OGG 1/2 expression in intestinal cell lines IEC-6 and Caco-2

“…It was also reported that apelin suppresses apoptosis of human and mouse osteoblasts, and the anti-apoptotic action is mediated via the APJ/PI-3 kinase/Akt signalling pathway [15,25]. Apelin also inhibited human vascular smooth muscle cells (VSMCs) apoptosis induced by serum deprivation and increased Bcl-2 protein expression, but decreased Bax protein expression [26]. Apelin also activated in VSMCs the extracellular signal-regulated protein kinase (ERK) and Akt (a downstream effector of phosphatidylinositol 3-kinase) [26].…”

Effects of Apelin-13 on Human Prostate Cancer Lines [Insan Prostat Kanseri Hucre Serilerinde Apelin-13'un Etkileri]

“…insan dil kanseri hücreleri üzerinde yapmış oldukları bir başka çalışmada, apelinin hücre canlılığını arttırdığını rapor etmişlerdir [57]. Çeşitli hücre tipleri üzerinde yapılan araştırmalarda apelin sinyallerinin hücrelerde anti-apoptotik etkiye neden olduğu bildirilmiştir [58][59][60]. …”