Elevation of plasma high-density lipoproteins inhibits development of experimental abdominal aortic aneurysms

Evelyn Torsney, Grisha Pirianov, Nicoletta Charolidi, Azza Shoreim, David Gaze, Slaveia Petrova, Ken Laing, Trevor Meisinger, Wanfen Xiong, B. Timothy Baxter, Gillian W. Cockerill

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Objective-Patients with abdominal aortic aneurysms have lower concentrations of high-density lipoproteins (HDLs), leading us to investigate whether increasing plasma HDLs could influence aneurysm formation. Methods and Results-Using the angiotensin II-induced hypercholesterolemic and the CaCl2-induced normocholesterolemic mouse model of AAA, we investigated the hypothesis that elevation of HDLs inhibits AAA. HDLs elevated before or at the time of AAA induction reduced AAA formation in both models but had no effect on early ruptures. Analysis of protein lysates from specific aortic segments demonstrated site-specific effects of HDLs on early signal transduction and cellular attrition. We found that HDLs reduced extracellular signal related kinases 1/2 activation in the suprarenal segment, while having no effect on p38 mitogen-associated protein kinase activation in any aortic segment and inhibiting c-Jun N-terminal kinase activation in all aortic segments. In addition, HDL elevation inhibited angiotensin II-induced apoptosis while inducing autophagy in the suprarenal segment of the aorta. Using Illumina gene array profiling we investigated the ability of HDL to modulate basal suprarenal aortic gene expression. Conclusion-Increasing plasma HDLs inhibit experimental AAA formation, independent of hypercholesterolemia via reduced extracellular signal related kinases 1/2 activation and alteration of the balance of cellular attrition. HDLs modulate genes involved in matrix remodelling, cell migration, and proliferation.

Original languageEnglish (US)
Pages (from-to)2678-2686
Number of pages9
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume32
Issue number11
DOIs
StatePublished - Nov 1 2012

Keywords

  • Abdominal aortic aneurysms
  • Apolipoprotein AI
  • Apoptosis
  • Autophagy
  • C-Jun N-terminal kinase
  • Phospho-extracellular signal related kinases 1/2

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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    Torsney, E., Pirianov, G., Charolidi, N., Shoreim, A., Gaze, D., Petrova, S., Laing, K., Meisinger, T., Xiong, W., Baxter, B. T., & Cockerill, G. W. (2012). Elevation of plasma high-density lipoproteins inhibits development of experimental abdominal aortic aneurysms. Arteriosclerosis, Thrombosis, and Vascular Biology, 32(11), 2678-2686. https://doi.org/10.1161/ATVBAHA.112.00009