Effectiveness of cyclooxygenase-2 inhibition in limiting abdominal aortic aneurysm progression in mice correlates with a differentiated smooth muscle cell phenotype

Kamalika Mukherjee, Jonathan M. Gitlin, Charles D. Loftin

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Abdominal aortic aneurysms (AAAs) are a chronic condition that often progress over years to produce a weakened aorta with increased susceptibility for rupture, and currently, there are no pharmacological treatments available to slow disease progression. AAA development has been characterized by increased expression of cyclooxygenase-2 (COX-2), and inactivation of COX-2 before disease initiation reduces AAA incidence in a mouse model of the disease. The current study determined the effectiveness of COX-2 inhibition on AAA progression when treatment was begun after initiation of the disease. COX-2 inhibitor treatment with celecoxib was initiated after angiotensin II-induced AAA formation in a strain of nonhyperlipidemic mice that we have previously identified as highly susceptible to AAA development. When analyzed at different time points during progression of the disease, celecoxib treatment significantly reduced the incidence and severity of AAAs. The celecoxib treatment also protected the mice from aortic rupture and death. The aneurysmal lesion displayed an altered smooth muscle cell (SMC) phenotype, whereas celecoxib treatment was associated with increased expression of differentiated SMC markers and reduced dedifferentiation marker expression during AAA progression. Maintenance of a differentiated SMC phenotype is associated with the effectiveness of COX-2 inhibition for limiting AAA progression in nonhyperlipidemic mice.

Original languageEnglish (US)
Pages (from-to)520-529
Number of pages10
JournalJournal of Cardiovascular Pharmacology
Volume60
Issue number6
DOIs
StatePublished - Dec 1 2012

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Abdominal Aortic Aneurysm
Cyclooxygenase 2
Celecoxib
Smooth Muscle Myocytes
Phenotype
Disease Progression
Aortic Rupture
Cyclooxygenase 2 Inhibitors
Incidence
Angiotensin II
Aorta
Rupture
Maintenance
Pharmacology

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

Cite this

Effectiveness of cyclooxygenase-2 inhibition in limiting abdominal aortic aneurysm progression in mice correlates with a differentiated smooth muscle cell phenotype. / Mukherjee, Kamalika; Gitlin, Jonathan M.; Loftin, Charles D.

In: Journal of Cardiovascular Pharmacology, Vol. 60, No. 6, 01.12.2012, p. 520-529.

Research output: Contribution to journalArticle

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