2. Academic Validation
  3. Role of prostaglandin D2 receptors in the pathogenesis of abdominal aortic aneurysm formation

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

  • Clin Sci (Lond). 2022 Mar 18;136(5):309-321. doi: 10.1042/CS20220031.
Neal L Weintraub  # 1 2,  Andra L Blomkalns  # 3,  Mourad Ogbi 1 2,  Tetsuo Horimatsu 1 2,  Tyler W Benson 1 2,  Yuqing Huo 2 4,  David J Fulton 2 5,  Gautam Agarwal 6,  Richard Lee 6,  Michael A Winkler 7,  Lufei Young 8,  Ken Fujise 9,  Avirup Guha 10,  Tohru Fukai 1 2,  Masuko Ushio-Fukai 1 2,  Xiaochun Long 1 2,  Brian H Annex 1 2,  Ha Won Kim 1 2
Affiliations

Affiliations

  • 1 Department of Medicine, College of Nursing at Augusta University, Augusta, GA, U.S.A.
  • 2 Vascular Biology Center, Medical College of Georgia, College of Nursing at Augusta University, Augusta, GA, U.S.A.
  • 3 Department of Emergency Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, U.S.A.
  • 4 Cellular Biology and Anatomy, College of Nursing at Augusta University, Augusta, GA, U.S.A.
  • 5 Pharmacology and Toxicology, College of Nursing at Augusta University, Augusta, GA, U.S.A.
  • 6 Surgery, College of Nursing at Augusta University, Augusta, GA, U.S.A.
  • 7 Radiology, College of Nursing at Augusta University, Augusta, GA, U.S.A.
  • 8 Physiological and Technological Nursing, College of Nursing at Augusta University, Augusta, GA, U.S.A.
  • 9 Division of Cardiology, Haborview Medical Center, University of Washington, Seattle, WA, U.S.A.
  • 10 Harrington Heart and Vascular Institute, Case Western Reserve University School of Medicine, Cleveland, OH, U.S.A.
  • # Contributed equally.
PMID: 35132998 DOI: 10.1042/CS20220031
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.

Keywords

abdominal aortic aneurysm; angiotensin converting enzyme 2; calcium chloride; fevipiprant; laropiprant; prostaglandin D2.

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