Title

Overexpression of prostaglandin E2 EP4 receptor improves cardiac function after myocardial infarction.

Document Type

Article

Publication Date

5-1-2018

Publication Title

J mol cell cardiol

Abstract

BACKGROUND:

Prostaglandin E2 (PGE2) signals through 4 separate G-protein coupled receptor sub-types to elicit a variety of physiologic and pathophysiological effects. We recently reported that PGE2 via its EP3 receptor could reduce cardiac contractility of isolated myocytes and the working heart preparation. We thus hypothesized that there is an imbalance in the EP3/EP4 ratio towards EP3 in the failing heart and that overexpression of EP4 in a mouse model of heart failure would improve cardiac function.

METHODS AND RESULTS:

Our hypothesis was tested in a mouse model of myocardial infarction (MI) with the use of AAV9-EP4 driven by the myosin heavy chain promoter to overexpress EP4 in the cardiac myocytes. Echocardiography was performed to assess cardiac function. We found that overexpression of EP4 improved shortening fraction (p = 0.0025), ejection fraction (p = 0.0003), and reduced left ventricular dimension at systole (p = 0.0013). Overexpression of EP4 also significantly reduced indices of cardiac hypertrophy and interstitial collagen fraction. Animals treated with AAV9-EP4 also had a significant decrease in TNFα mRNA expression and in the number of macrophages and T cells migrated post MI coupled with a reduction in the expression of iNOS.

CONCLUSION:

Overexpression of EP4 improves cardiac function post MI. This may be mediated through reductions in adverse cardiac remodeling or via inhibition of cytokine/chemokine production.

Medical Subject Headings

Animals; Calcium-Binding Proteins; Cardiomegaly; Cell Movement; Cell Polarity; Collagen; Cytokines; Dependovirus; Heart; Heart Ventricles; Macrophages; Male; Matrix Metalloproteinase 2; Mice, Inbred C57BL; Myocardial Infarction; Myocytes, Cardiac; Phosphorylation; RNA, Messenger; Receptors, Prostaglandin E, EP4 Subtype; T-Lymphocytes; Tumor Necrosis Factor-alpha

PubMed ID

29522761

Volume

118

First Page

1

Last Page

12

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