Microsomal Prostaglandin E Synthase-1 Expression by Aortic Smooth Muscle Cells Attenuates the Differentiated Phenotype

Oreoluwa O. Adedoyin, Charles D. Loftin

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)127-142
Number of pages16
JournalJournal of Cardiovascular Pharmacology
Volume68
Issue number2
DOIs
StatePublished - Aug 1 2016

Bibliographical note

Funding Information:
Supported by the National Heart, Lung, and Blood Institute, NIH [HL083122 to C.D.L.].

Publisher Copyright:
Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.

Keywords

  • cyclooxygenase-2
  • microsomal prostaglandin E synthase-1
  • smooth muscle cell differentiation

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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