The development of numerous types of cardiovascular disease is associated with alteration of the vascular smooth muscle cell (SMC) phenotype. We have previously shown that abdominal aortic aneurysm progression in a mouse model of the disease is associated with reduced differentiation of SMCs within the lesion and that cyclooxygenase-2 (COX-2) is critical to initiation and progression of the aneurysms. The current studies used human aortic SMC (hASMC) cultures to better characterize mechanisms responsible for COX-2-dependent modulation of the SMC phenotype. Depending on the culture conditions, hASMCs expressed multiple characteristics of a differentiated and contractile phenotype, or a dedifferentiated and secretory phenotype. The pharmacological inhibition of COX-2 promoted the differentiated phenotype, whereas treatment with the COX-2-derived metabolite prostaglandin E2 (PGE2) increased characteristics of the dedifferentiated phenotype. Furthermore, pharmacological inhibition or siRNA-mediated knockdown of microsomal prostaglandin E synthase-1 (mPGES-1), the enzyme that functions downstream of COX-2 during the synthesis of PGE2, significantly increased expression of characteristics of the differentiated SMC phenotype. Therefore, our findings suggest that COX-2 and mPGES-1-dependent synthesis of PGE2 contributes to a dedifferentiated hASMC phenotype and that mPGES-1 may provide a novel pharmacological target for treatment of cardiovascular diseases where altered SMC differentiation has a causative role.
|Number of pages
|Journal of Cardiovascular Pharmacology
|Published - Aug 1 2016
Bibliographical noteFunding Information:
Supported by the National Heart, Lung, and Blood Institute, NIH [HL083122 to C.D.L.].
Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.
- microsomal prostaglandin E synthase-1
- smooth muscle cell differentiation
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine