title: Elevation of plasma high-density lipoproteins inhibits development of experimental abdominal aortic aneurysms.
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.
  
  
  RESULTS
  Using the angiotensin II-induced hypercholesterolemic and the CaCl(2)-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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Clinical Sciences, St George's University of London, London, United Kingdom.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Torsney
authors.forename: Grisha
authors.initials: G
authors.lastname: Pirianov
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Charolidi
authors.forename: Azza
authors.initials: A
authors.lastname: Shoreim
authors.forename: David
authors.initials: D
authors.lastname: Gaze
authors.forename: Slaveia
authors.initials: S
authors.lastname: Petrova
authors.forename: Ken
authors.initials: K
authors.lastname: Laing
authors.forename: Trevor
authors.initials: T
authors.lastname: Meisinger
authors.forename: Wanfen
authors.initials: W
authors.lastname: Xiong
authors.forename: B Timothy
authors.initials: BT
authors.lastname: Baxter
authors.forename: Gillian W
authors.initials: GW
authors.lastname: Cockerill
mesh_terms: D000804:Angiotensin II; D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D017544:Aortic Aneurysm, Abdominal / Q000097:blood / Q000209:etiology / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D001019:Aortic Rupture / Q000097:blood / Q000209:etiology / Q000517:prevention & control; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D001343:Autophagy; D002122:Calcium Chloride; D004195:Disease Models, Animal; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D006937:Hypercholesterolemia / Q000150:complications / Q000235:genetics; D007279:Injections, Subcutaneous; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008075:Lipoproteins, HDL / Q000008:administration & dosage / Q000097:blood*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D015398:Signal Transduction; D013997:Time Factors; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D008075:Lipoproteins, HDL; D000804:Angiotensin II; D048031:JNK Mitogen-Activated Protein Kinases; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D002122:Calcium Chloride