title: High-density lipoprotein therapy inhibits Porphyromonas gingivalis-induced abdominal aortic aneurysm progression.
abstract: Clinical and experimental studies have highlighted the potential implication of periondontal bacteria contamination in the pathogenesis of abdominal aortic aneurysms (AAA). In addition to their role in reverse cholesterol transport, high-density lipoproteins (HDLs) display multiple functions, including anti-inflammatory and lipopolysaccharide scavenging properties. Low plasma levels of HDL-cholesterol have been reported in AAA patients. We tested the effect of a HDL therapy in Sprague-Dawley rat model of AAA, obtained by intraluminal elastase infusion followed by repeated injections of Porphyromonas gingivalis (Pg). HDLs, isolated by ultracentrifugation of plasma from healthy human volunteers, were co-injected intravenously (10 mg/kg) with Pg (1.107 Colony Forming Unit) one, eight and 15 days after elastase perfusion. Rats were sacrificed one week after the last injection. Our results show that Pg injections promote the formation of a persistent neutrophil-rich thrombus associated with increased aortic diameter in this AAA model. HDLs significantly reduced the increased AAA diameter induced by Pg. Histology showed the onset of a healing process in the Pg/HDL group. HDL injections also reduced neutrophil activation in Pg-injected rats associated with decreased cytokine levels in conditioned media and plasma. Scintigraphic analysis showed an intense uptake of 99mTc-HDL by the AAA suggesting that HDLs could exert their beneficial effect by acting directly on the thrombus components. HDL supplementation may therefore constitute a new therapeutic tool for AAA treatment.
authors.affiliation: Sandrine Delbosc, Inserm u1148 Laboratory for Vascular Translational Science, 46 Rue Henri Huchard, 75018 Paris, France, Tel.: +33 1 40 25 86 05, E-mail: sandrine.delbosc@inserm.fr / olivier.meilhac@inserm.fr.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Delbosc
authors.forename: Martin
authors.initials: M
authors.lastname: Rouer
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Alsac
authors.forename: Liliane
authors.initials: L
authors.lastname: Louedec
authors.forename: Faisal
authors.initials: F
authors.lastname: Al Shoukr
authors.forename: François
authors.initials: F
authors.lastname: Rouzet
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Michel
authors.forename: Olivier
authors.initials: O
authors.lastname: Meilhac
mesh_terms: D000818:Animals; D017544:Aortic Aneurysm, Abdominal / Q000188:drug therapy* / Q000209:etiology; D016866:Bacteroidaceae Infections / Q000150:complications / Q000188:drug therapy*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D006801:Humans; D008075:Lipoproteins, HDL / Q000627:therapeutic use*; D008297:Male; D018375:Neutrophil Activation / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects* / Q000473:pathology; D016966:Porphyromonas gingivalis / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016207:Cytokines; D008075:Lipoproteins, HDL
keywords: Abdominal aortic aneurysm; Poprhyromonas gingivalis; high-density lipoproteins; neutrophils