ß1-Adrenoceptor antibody-induced increase in soluble CD40 ligand release in chronic periodontitis patients: role of prostaglandin E(2).

In this paper, we demonstrate that circulating antibodies from chronic periodontitis patients reacting with atrial ß(1)-adrenoceptors (ß(1)-ARs) act as an inducer of soluble CD40 ligand (sCD40L) release and prostaglandin E(2) (PGE(2)) generation. By enzyme-linked immunosorbent assay using ß(1) synthetic peptide (with an amino acid sequence identical to the second loop of human myocardial ß(1)-ARs) as a coating antigen, we demonstrated reactivity against the second extracellular loop on human myocardial ß(1)-ARs. This autoantibody present in the serum of chronic periodontitis patients was significantly correlated with the release of sCD40L and PGE(2). The release of sCD40L was blunted by atenolol, SP600125 and ß(1) synthetic peptide, and PGE(2) generation was inhibited by DuP 697 and slightly by FR122049. The effects of the antibody incubated with isolated rat atria upregulated sCD40L release with an increase of PGE(2) production and c-Jun N-terminal kinase phosphorylation. These results indicate that in chronic periodontitis patients, there is a positive association between sCD40L release and PGE(2) generation via the action of ß(1)-AR antibodies.

Role of anti-ß1 adrenergic antibodies from patients with periodontitis in cardiac dysfunction.

BACKGROUND: The presence of serum autoantibodies against ß(1) adrenoreceptors (ß(1)-ARs) in human gingival fibroblast from patients with periodontitis inhibits primary cell-specific growth and induces over-expression of pro-inflammatory mediators. Serum ß(1)-AR autoantibodies from patients with periodontitis react with myocardium and modify cardiac contractility. The relationship between the presence of serum ß(1)-AR autoantibodies and alterations in heart rate variability (HRV) was also studied. METHODS: An enzyme-linked immunosorbent assay (ELISA) using cardiac and gingival fibroblast membranes or synthetic peptides corresponding to the second extracellular loop of human ß(1)-AR was used to detect serum autoantibodies. The HRV was assessed from RR interval files generated from 22:00 to 08:00 hours. The autoantibody effects on contractility were measured on spontaneous rat isolated atria. RESULTS: Circulating autoantibodies from 36 patients with periodontitis and 20 healthy individuals (controls) interacted with fibroblasts, the cardiac surface, and ß(1)-AR synthetic peptides. The distributions of serum antibodies against gingival and myocardium membranes and ß(1)-AR synthetic peptide were 88.8%, 77.7%, and 92.8%, respectively. Moreover, 88.5% of patients with periodontitis whose sera were positive against ß(1)-AR synthetic peptide had decreased HRV. The corresponding affinity-purified anti-ß(1)-AR peptide IgG displayed partial agonist-like activity modifying the isolated atria contractility. CONCLUSION: This manuscript describes that patients with periodontitis showed increased levels of serum IgG with reactive activity against ß(1)-AR. Those patients demonstrated decrease in heart rate, and IgG derived from their sera induced aberrant contractility of heart atrium. We propose that periodontitis increases the risk of cardiovascular diseases, although it increases anti-ß(1)-AR autoantibody that alters myocardial contractility.

Autoantibodies to the ß(1)-Adrenoceptor from Patients with Periodontitis as a Risk Factor for Cardiac Dysfunction.

The presence of serum autoantibodies in periodontitis (P) patients against ß(1)-adrenoceptor (ß(1)-AR), using cardiac membranes or a synthetic ß(1)-AR peptide corresponding to the second extracellular loop of human ß(1)-AR as antigens, permit us to detect circulating antibody from 40 P patients but not in 20 normal individuals (control). Simultaneously, the P patients exhibited a decrease in HRV. Anti-ß(1)-AR IgG titters correlated with the decrease in HRV of the same patients and the anti-ß(1)-AR peptide IgG displayed partial agonist-like activity and modified the contractility of isolated atria, produced cyclic nucleotides, and inhibited the ß(1)-AR agonistic activity of isoproterenol. We demonstrated in this study an association between periodontitis infection and an increased risk of cardiac disease, thereby highlighting the role of anti-ß(1)-AR autoantibodies in alteration of myocardial contractility.