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).
Atherosclerosis and its subsequent clinical complications, such as stroke or myocardial infarction, 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
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
Porphyromonas gingivalis Participates in Pathogenesis of Human Abdominal Aortic Aneurysm by Neutrophil
Activation. Proof of Concept in Rats
Gum disease linked to Atherosclerosis (30/09/2011)
Sandrine Delbosc (1),(2), Jean-Marc Alsac (1),(4), Clement Journe (1),(2), Liliane Louedec (1),(2), Yves Castier (3), Martine Bonnaure-Mallet (5), Raymond Ruimy (6), Patrick Rossignol (7), Philippe Bouchard (2),(8), Jean-Baptiste Michel (1),(2), Olivier Meilhac (1),(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)