Role of prostaglandin D2 receptors in the pathogenesis of abdominal aortic aneurysm formation

Neal L. Weintraub
,
Andra L. Blomkalns
,
Mourad Ogbi
,
Tetsuo Horimatsu
,
Tyler W. Benson
,
Yuqing Huo

Scholary Output:

Contribution to journal

Article

Peer-review

Abstract

Prostaglandin D2 (PGD2) released from immune cells or other cell types activates its receptors, D prostanoid receptor (DP)1 and 2 (DP1 and DP2), to promote inflammatory responses in allergic and lung diseases. Prostaglandin-mediated inflammation may also contribute to vascular diseases such as abdominal aortic aneurysm (AAA). However, the role of DP receptors in the pathogenesis of AAA has not been systematically investigated. In the present study, DP1-deficient mice and pharmacological inhibitors of either DP1 or DP2 were tested in two distinct mouse models of AAA formation: angiotensin II (AngII) infusion and calcium chloride (CaCl2) application. DP1-deficient mice [both heterozygous (DP1+/-) and homozygous (DP1-/-)] were protected against CaCl2-induced AAA formation, in conjunction with decreased matrix metallopeptidase (MMP) activity and adventitial inflammatory cell infiltration. In the AngII infusion model, DP1+/- mice, but not DP1-/- mice, exhibited reduced AAA formation. Interestingly, compensatory up-regulation of the DP2 receptor was detected in DP1-/- mice in response to AngII infusion, suggesting a potential role for DP2 receptors in AAA. Treatment with selective antagonists of DP1 (laropiprant) or DP2 (fevipiprant) protected against AAA formation, in conjunction with reduced elastin degradation and aortic inflammatory responses. In conclusion, PGD2 signaling contributes to AAA formation in mice, suggesting that antagonists of DP receptors, which have been extensively tested in allergic and lung diseases, may be promising candidates to ameliorate AAA.

Publication Information

Output type

Scholary Output:

Contribution to journal

Article

Peer-review

Original language

English (US)

Pages from-to (Number of pages)

Pages 309-321 (13 pages)

Journal (Volume, Issue Number)

Clinical science (London, England : 1979) (Volume 136, Issue 5)

Publication milestones

Published - 03/18/2022

Publication status

Published - 03/18/2022

ISSN

0143-5221

Publication IDs

PubMed: 35132998
Scopus: 85125553861
PubMed: 35132998
ORCID: /0000-0002-0305-4122/work/124760266
ORCID: /0000-0003-0253-1174/work/172679175

Access to documents

10.1042/CS20220031

Link

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