Angiotensin II upregulates the expression of placental growth factor in human vascular endothelial cells and smooth muscle cells

Abstract

BackgroundAtherosclerosis is now recognized as a chronic inflammatory disease. Angiotensin II (Ang II) is a critical factor in inflammatory responses, which promotes the pathogenesis of atherosclerosis. Placental growth factor (PlGF) is a member of the vascular endothelial growth factor (VEGF) family cytokines and is associated with inflammatory progress of atherosclerosis. However, the potential link between PlGF and Ang II has not been investigated. In the current study, whether Ang II could regulate PlGF expression, and the effect of PlGF on cell proliferation, was investigated in human vascular endothelial cells (VECs) and smooth muscle cells (VSMCs).ResultsIn growth-arrested human VECs and VSMCs, Ang II induced PlGF mRNA expression after 4 hour treatment, and peaked at 24 hours. 10-6 mol/L Ang II increased PlGF protein production after 8 hour treatment, and peaked at 24 hours. Stimulation with Ang II also induced mRNA expression of VEGF receptor-1 and -2(VEGFR-1 and -2) in these cells. The Ang II type I receptor (AT1R) antagonist blocked Ang II-induced PlGF gene expression and protein production. Several intracellular signals elicited by Ang II were involved in PlGF synthesis, including activation of protein kinase C, extracellular signal-regulated kinase 1/2 (ERK1/2) and PI3-kinase. A neutralizing antibody against PlGF partially inhibited the Ang II-induced proliferation of VECs and VSMCs. However, this antibody showed little effect on the basal proliferation in these cells, whereas blocking antibody of VEGF could suppress both basal and Ang II-induced proliferation in VECs and VSMCs.ConclusionOur results showed for the first time that Ang II could induce the gene expression and protein production of PlGF in VECs and VSMCs, which might play an important role in the pathogenesis of vascular inflammation and atherosclerosis.

Placental Growth Factor as a Predictor of Cardiovascular Events in Patients with CKD from the NARA-CKD Study

“…6,7 Third, because the expression of PlGF in vascular cells is enhanced by angiotensin II and aldosterone, PlGF is thought to be a downstream target of the renin-angiotensin system (RAS) and mineralocorticoid receptor. [31][32][33] In CKD, there is isolated or synergistic RAS and mineralocorticoid receptor hyperactivity, which is possibly mediated by upregulation of PlGF. 34,35 Further clinical research is needed to investigate the association between PlGF levels and RAS.…”

First trimester serum markers to predict preeclampsia

“…At the same time PlGF has been described to be expressed in adult endothelial cells as well as smooth muscle cells [17]. Hence, serum levels of PlGF in pregnant women are a combination of secretion/release from different trophoblast populations in combination with secretion/release from different maternal vascular cells.…”

Urotensin II Stimulates Vascular Endothelial Growth Factor Secretion From Adventitial Fibroblasts in Synergy With Angiotensin II

“…7-9 Recent studies have shown that UII and Ang II may induce vascular remodeling in the adventitia by inducing the differentiation, migration and proliferation and collagen synthesis in adventitial fibroblasts. 3, 10 The above effects are mainly achieved through the binding of UII and Ang II with their respective receptors to activate downstream pathways such as mitogen-activated protein kinase (MAPK), protein kinase C (PKC) and calcium channels. 3 However, the exact mechanisms by which UII and Ang II mediate vascular remodeling in the adventitia are still largely unclear.…”

“…10 Jin et al found that Flt-1 was expressed in adventitial fibroblasts; however, little is known about whether adventitial fibroblasts serve as a novel source of VEGF. 17 The effects of Ang II and UII on VEGF expression have been mostly studied in vascular endothelial cells and smooth muscle cells.…”

“…Ang II has been reported to induce VEGF expression in human endothelial cells and smooth muscle cells. 10 Furthermore, researchers have shown that VEGF is involved in Ang II-induced cell proliferation and collagen synthesis. 9, 18 However, Albertin et al found that UII did not affect VEGF expression in human endothelial cells.…”