Telomerase deficiency in bone marrow-derived cells attenuates angiotensin II-induced abdominal aortic aneurysm formation

Hannes M. Findeisen, Florence Gizard, Yue Zhao, Dianne Cohn, Elizabeth B. Heywood, Karrie L. Jones, David H. Lovett, Deborah A. Howatt, Alan Daugherty, Dennis Bruemmer

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


Objective-: Abdominal aortic aneurysms (AAA) are an age-related vascular disease and an important cause of morbidity and mortality. In this study, we sought to determine whether the catalytic component of telomerase, telomerase reverse transcriptase (TERT), modulates angiotensin (Ang) II-induced AAA formation. Methods and results-: Low-density lipoprotein receptor-deficient (LDLr-/-) mice were lethally irradiated and reconstituted with bone marrow-derived cells from TERT-deficient (TERT-/-) mice or littermate wild-type mice. Mice were placed on a diet enriched in cholesterol, and AAA formation was quantified after 4 weeks of Ang II infusion. Repopulation of LDLr-/- mice with TERT-/- bone marrow-derived cells attenuated Ang II-induced AAA formation. TERT-deficient recipient mice revealed modest telomere attrition in circulating leukocytes at the study end point without any overt effect of the donor genotype on white blood cell counts. In mice repopulated with TERT-/- bone marrow, aortic matrix metalloproteinase-2 (MMP-2) activity was reduced, and TERT-/- macrophages exhibited decreased expression and activity of MMP-2 in response to stimulation with Ang II. Finally, we demonstrated in transient transfection studies that TERT overexpression activates the MMP-2 promoter in macrophages. Conclusion-: TERT deficiency in bone marrow-derived macrophages attenuates Ang II-induced AAA formation in LDLr-/- mice and decreases MMP-2 expression. These results point to a previously unrecognized role of TERT in the pathogenesis of AAA.

Original languageEnglish
Pages (from-to)253-260
Number of pages8
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Issue number2
StatePublished - Feb 2011


  • aneurysms
  • angiotensin II
  • gene expression
  • macrophages
  • matrix metalloproteinase
  • telomerase

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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