Regulation of bFGF-induced effects on rat aortic smooth muscle cells by β3-adrenergic receptors

Yingzi Chang; Lei Alena Dagat; Aisha Yusuf; Yusuf Zahriya; Kotryna Staputyte; Emma Worley; Alex Holt; Natalie Canuteson; Vereena Messieha; Kasey Halila

doi:10.1016/j.crphar.2022.100094

Regulation of bFGF-induced effects on rat aortic smooth muscle cells by β₃-adrenergic receptors

Curr Res Pharmacol Drug Discov. 2022 Mar 7:3:100094. doi: 10.1016/j.crphar.2022.100094. eCollection 2022.

Authors

Affiliations

¹ Department of Pharmacology, A.T. Still University, Kirksville College of Osteopathic Medicine, Kirksville, MO, 63501, USA.
² Truman State University, Kirksville, MO, 63501, USA.

Abstract

Background: Basic fibroblast growth factor (bFGF)-mediated vascular smooth muscle cell (VSMC) proliferation and migration play an important role in vascular injury-induced neointima formation and subsequent vascular restenosis, a major event that hinders the long-term success of angioplasty. The function of β₃-adrenergic receptors (β₃-ARs) in vascular injury-induced neointima formation has not yet been defined.

Objectives: Our current study explored the possible role of β₃-ARs in vascular injury-induced neointima formation by testing its effects on bFGF-induced VSMC migration and proliferation.

Methods: β₃-AR expression in rat carotid arteries was examined at 14 days following a balloon catheter-induced injury. The effects of β₃-AR activation on bFGF-induced rat aortic smooth muscle cell proliferation, migration, and signaling transduction (including extracellular-signal-regulated kinase/mitogen activated protein kinase, ERK/MAPK and Protein kinase B, AKT) were tested.

Results: We found that vascular injury induced upregulation of β₃-ARs in neointima. Pretreatment of VSMCs with a selective β₃-AR agonist, CL316,243 significantly potentiated bFGF-induced cell migration and proliferation, and ERK and AKT phosphorylation. Our results also revealed that suppressing phosphorylation of ERK and AKT blocked bFGF-induced cell migration and that inhibiting AKT phosphorylation reduced bFGF-mediated cell proliferation.

Conclusion: Our results suggest that activation of β₃-ARs potentiates bFGF-mediated effects on VSMCs by enhancing bFGF-mediated ERK and AKT phosphorylation and that β₃-ARs may play a role in vascular injury-induced neointima formation.

Keywords: CL316,243; ERK/AKT phosphorylation; ERK/MAPK, extracellular-signal-regulated kinase/mitogen activated protein kinase; Neointima; PI3K/AKT, phosphatidylinositol 3-kinase and Akt (protein kinase B); VSMC migration; VSMC proliferation; VSMC, vascular smooth muscle cell; bFGF, basic fibroblast growth factor; β3-AR, β3-adrenergic receptor.