Excessive EP4 Signaling in Smooth Muscle Cells Induces Abdominal Aortic Aneurysm by Amplifying Inflammation.

ABSTRACT:

Objective

Excessive prostaglandin E₂ production is a hallmark of abdominal aortic aneurysm (AAA). Enhanced expression of prostaglandin E₂ receptor EP4 (prostaglandin E receptor 4) in vascular smooth muscle cells (VSMCs) has been demonstrated in human AAAs. Although moderate expression of EP4 contributes to vascular homeostasis, the roles of excessive EP4 in vascular pathology remain uncertain. We aimed to investigate whether EP4 overexpression in VSMCs exacerbates AAAs. Approach and Results: We constructed mice with EP4 overexpressed selectively in VSMCs under an SM22α promoter (EP4-Tg). Most EP4-Tg mice died within 2 weeks of Ang II (angiotensin II) infusion due to AAA, while nontransgenic mice given Ang II displayed no overt phenotype. EP4-Tg developed much

SUBMITTER: Hiromi T 

PROVIDER: S-EPMC7253191 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature