title: Development of abdominal aortic aneurysm is decreased in mice with plasma phospholipid transfer protein deficiency.
abstract: Plasma phospholipid transfer protein (PLTP) increases the circulating levels of proatherogenic lipoproteins, accelerates blood coagulation, and modulates inflammation. The role of PLTP in the development of abdominal aortic aneurysm (AAA) was investigated by using either a combination of mechanical and elastase injury at one site of mouse aorta (elastase model) or continuous infusion of angiotensin II in hyperlipidemic ApoE-knockout mice (Ang II model). With the elastase model, complete PLTP deficiency was associated with a significantly lower incidence and a lesser degree of AAA expansion. With the Ang II model, findings were consistent with those in the elastase model, with a lower severity grade in PLTP-deficient mice, an intermediate phenotype in PLTP-deficient heterozygotes, and a blunted effect of the PLTP-deficient trait when restricted to bone marrow-derived immune cells. The protective effect of whole-body PLTP deficiency in AAA was illustrated further by a lesser degree of adventitia expansion, reduced elastin degradation, fewer recruited macrophages, and less smooth muscle cell depletion in PLTP-deficient than in wild-type mice, as evident from comparative microscopic analysis of aorta sections. Finally, cumulative evidence supports the association of PLTP deficiency with reduced expression and activity levels of matrix metalloproteinases, known to degrade elastin and collagen. We conclude that PLTP can play a significant role in the pathophysiology of AAA.
authors.affiliation: UMR866, University of Burgundy, Dijon, France. valerie.deckert@u-bourgogne.fr
authors.forename: Valérie
authors.initials: V
authors.lastname: Deckert
authors.forename: Benjamin
authors.initials: B
authors.lastname: Kretz
authors.forename: Ahmed
authors.initials: A
authors.lastname: Habbout
authors.forename: Kawtar
authors.initials: K
authors.lastname: Raghay
authors.forename: Jérôme
authors.initials: J
authors.lastname: Labbé
authors.forename: Nicolas
authors.initials: N
authors.lastname: Abello
authors.forename: Catherine
authors.initials: C
authors.lastname: Desrumaux
authors.forename: Thomas
authors.initials: T
authors.lastname: Gautier
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Lemaire-Ewing
authors.forename: Guillaume
authors.initials: G
authors.lastname: Maquart
authors.forename: Naig
authors.initials: N
authors.lastname: Le Guern
authors.forename: David
authors.initials: D
authors.lastname: Masson
authors.forename: Eric
authors.initials: E
authors.lastname: Steinmetz
authors.forename: Laurent
authors.initials: L
authors.lastname: Lagrost
mesh_terms: D000804:Angiotensin II; D000818:Animals; D001011:Aorta / Q000473:pathology; D017544:Aortic Aneurysm, Abdominal / Q000150:complications / Q000378:metabolism* / Q000473:pathology*; D001057:Apolipoproteins E / Q000172:deficiency; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004549:Elastin / Q000378:metabolism; D007249:Inflammation / Q000150:complications / Q000473:pathology; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010196:Pancreatic Elastase; D049294:Phospholipid Transfer Proteins / Q000172:deficiency* / Q000378:metabolism*
chemical_list: D001057:Apolipoproteins E; D016207:Cytokines; D049294:Phospholipid Transfer Proteins; C510091:phospholipid transfer protein, mouse; D000804:Angiotensin II; D004549:Elastin; D010196:Pancreatic Elastase