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Paris, 5 May 2011
Press release
Healthy gums... for healthy blood vessels
Researchers from Inserm Mixed Research Unit 698 "Hémostase, bio-ingénierie,
immunopathologie et remodelage cardiovasculaires" at the Bichat hospital and
University Paris Diderot, directed by Dr Jean-Baptiste Michel, in collaboration with
vascular surgeons from AP-HP (Bichat and Georges Pompidou hospitals) and the
periodontology teams at AP-HP Rothschild Hospital and Rennes, have demonstrated a
strong link between periodontitis, an inflammation of the tissues supporting the teeth,
and the development of abdominal aortic aneurysms (AAA).
The results of this work have been published in the journal PloS One, which can be accessed on-line.
Atherosclerosis and its subsequent clinical complications, such as strokes or myocardial
infarctions, are the leading cause of death in the industrialized countries. Abdominal aortic
aneurysms (AAA) are one particular clinical manifestation of atherothrombosis in the aorta.
They affect up to 9% of the adult population and are responsible for 1-2% of deaths among men
over the age of 65.
AAA are characterized by formation of a thrombus (blood clot) in the lumen of the aorta which
participates in the degradation of the aorta wall and its eventual rupture, resulting in death;
known also as "aneurysm rupture". The thrombus does not block the aorta; rather, it acts as a
source of enzymes, which digest the wall of the blood vessel, and as an anchorage point for
circulating bacteria.
However, in recent years, research has shown that treatment with the antibiotic, doxycycline,
reduces the growth of AAA. Recent studies also detected periodontal bacteria in atherosclerotic
samples taken from Japanese patients. However, until now, no evidence has been obtained
from animal models to prove any causal link.
In their work, the researchers from Inserm and AP-HP, coordinated by Olivier Meilhac, have
shown that bacteria responsible for gum/periodontal diseases such as Porphyromonas
gingivalis are found in samples taken from human aortic aneurysms. Olivier Meilhac and his
team therefore sought to discover the mechanisms by which these bacteria, present in the
gums, could be found in the aorta.
Working with rats, the researchers discovered that larger aneurysms developed in animals
which had been injected with P.gingivalis and these rats exhibited an absence of healing,
similar to the situation observed in humans. The non-healing of the thrombus could be
explained by a chronic recruitment of immune cells, known as neutrophils, which are normally
responsible for defending the organism and whose activation led to release of elastase which
digests the wall of the aorta (see photograph below).
AAA in a rat without Pg
Healing
AAA in a rat injected with Pg
Accumulation of neutrophils Details of the thrombus (magnification of upper photographs ×40, lower photographs x200 and framed x1000) in the
case of an abdominal aortic aneurysm in the normal state (left column) and in the presence of bacterium
Porphyromonas gingivalis (right column).The thrombus grows in the presence of the bacteria and healing is reduced.
Copyright J-B. Michel-O. Meilhac/Inserm However, the presence of these neutrophils on the luminal face of the thrombus (in humans)
can only be explained by postulating the presence of an agent which attracts them. For this
reason, the team made the hypothesis that (weakly pathogenic) bacteria might cause this
chronic recruitment phenomenon. Indeed, the histology showed that when rats had been
injected with P. gingivalis, many more neutrophils accumulated on the surface of the thrombus,
whereas non-injected rats began to heal and the presence of neutrophils was rare.
The researchers consider that the recruitment of these cells may be due to low-level but
recurring bacterial infections of oral origin. "In the long-term, these results could make it
possible to slow or even stop the progression of abdominal aortic aneurysms, by treating
periodontal disease or by applying suitable antibiotic therapies," conclude the authors. The team
of Olivier Meilhac aims, in future, to verify the possible application of these results to other
clinical manifestations of atherothrombosis, such as carotid artery and coronary diseases.
Pour en savoir plus
Source
Porphyromonas gingivalis Participates in Pathogenesis of Human Abdominal Aortic
Aneurysm by Neutrophil Activation. Proof of Concept in Rats
Sandrine Delbosc1,2, Jean-Marc Alsac1,4, Clement Journe1,2, Liliane Louedec1,2, Yves Castier3, Martine
Bonnaure-Mallet5, Raymond Ruimy6, Patrick Rossignol7, Philippe Bouchard2,8, Jean-Baptiste Michel1,2, Olivier
Meilhac1,2*
1 INSERM (Institut National de la Sante´ et de la Recherche Médicale) U698, Paris, France,
2 Université Denis Diderot, Paris, France,
3 Service de chirurgie thoracique et vasculaire, Hôpital Xavier Bichat-Claude Bernard, AP-HP (Assistance Publique - Hôpitaux
de Paris), Paris, France,
4 Service de chirurgie cardiovasculaire, Hôpital Européen Georges Pompidou, AP-HP (Assistance Publique - Hôpitaux de
Paris), Paris, France,
5 Equipe de Microbiologie, UPRES-EA (Unité Propre de Recherche de l’Enseignement Supérieur-Equipe d’Accueil) 1254,
Université Européenne de Bretagne, Université de Rennes I, Rennes, France,
6 Service de bactériologie et virologie, Hôpital Xavier Bichat-Claude Bernard, AP-HP (Assistance Publique - Hôpitaux de Paris),
Paris, France,
7 CHU (Centre Hospitalier Universitaire) de Nancy, CIC (Centre d’Investigation Clinique); CIC9501; Université Nancy, Faculté
de Médecine; Inserm, U961, Vandoeuvre lès Nancy, France; Service de médecine vasculaire et hypertension, Hôpital Europeen
Georges Pompidou, Paris, France,
8 Département de Parodontologie, Service d’odontologie, Hôpital Garancière Rothschild, AP-HP (Assistance Publique Hôpitaux de Paris)
PloS One, http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0018679
Contact chercheur
Olivier Meilhac
Directeur de Recherche Inserm *
Unité Inserm 698 "Hémostase, Bio-Ingénierie et Remodelages Cardiovasculaires"
et Bichat Stroke Center
Hôpital Bichat, secteur Claude Bernard
Tel : 01-40-25-86-11
[email protected]
www.u698.fr
Press contact
Séverine Ciancia
[email protected]
Tel: +33 (0)1 44 23 60 86