Inhibition of EP4 Signaling Attenuates Aortic Aneurysm Formation

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Inhibition of EP4 Signaling Attenuates Aortic Aneurysm Formation

BACKGROUND Aortic aneurysm is a common but life-threatening disease among the elderly, for which no effective medical therapy is currently available. Activation of prostaglandin E(2) (PGE(2)) is known to increase the expression of matrix metalloproteinase (MMP) and the release of inflammatory cytokines, and may thus exacerbate abdominal aortic aneurysm (AAA) formation. We hypothesized that sele...

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Heat shock protein 90 inhibition by 17-DMAG attenuates abdominal aortic aneurysm formation in mice.

Abdominal aortic aneurysm (AAA) is a common degenerative vascular disease whose pathogenesis is associated with activation of multiple signaling pathways including Jun NH2-terminal kinases (JNK) and NF-κB. It is now well recognized that these pathways are chaperoned by the heat shock protein 90 (Hsp90), suggesting that inhibition of Hsp90 may be a novel strategy for inhibiting AAAs. The aim of ...

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Mast cell tryptase deficiency attenuates mouse abdominal aortic aneurysm formation.

RATIONALE Mast cells (MCs) contribute to the formation of abdominal aortic aneurysms (AAAs) by producing biologically active mediators. Tryptase is the most abundant MC granule protein and participates in MC activation, protease maturation, leukocyte recruitment, and angiogenesis-all processes critical to AAA pathogenesis. OBJECTIVE To test the hypothesis that tryptase participates directly i...

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Aortic Aneurysm Formation

The development of a saccular (nondissecting) aortic aneurysm follows the destruction of the connective tissue in the media, in particular the elastic lamellae. The vessel wall is then unable to withstand the expansile force of each systolic contraction. The current view is that the great majority of aortic aneurysms, .90% of which are below the renal arteries, are associated with atheroscleros...

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KLF4 regulates abdominal aortic aneurysm morphology and deletion attenuates aneurysm formation.

BACKGROUND KLF4 mediates inflammatory responses after vascular injury/disease; however, the role of KLF4 in abdominal aortic aneurysms (AAAs) remains unknown. The goals of the present study were to (1) determine the role of KLF4 in experimental AAA; and (2) determine the effect of KLF4 on smooth muscle (SM) cells in AAAs. METHODS AND RESULTS KLF4 expression progressively increased at days 3, ...

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ژورنال

عنوان ژورنال: PLoS ONE

سال: 2012

ISSN: 1932-6203

DOI: 10.1371/journal.pone.0036724