Abstract 1757: Immune Response To P. gingivalis Antigens Exacerbates Angiotensin II Dependent Hypertension And Vascular Dysfunction
Periodontitis is a purported risk factor for cardiovascular disease however the mechanisms linking these clinical entities are poorly defined. We recently found that T cells are essential for development of hypertension and that hypertension causes recruitment of effector-like T cells into the perivascular fat. We hypothesized that T cell activation by a periodontal pathogen such as Porphyromonas gingivalis (Pg), could augment hypertension by increasing levels of activated T cells. Lysates from Pg when administered with IL12, have been shown to elicit a TH1-type immune response and increase circulating TH1 effector T cells. We therefore immunized C57Bl6/J mice with Pg lysate and co-treated the animals with IL-12 on day 1 and 3 weeks later. Low dose angiotensin II (0.3 mg/day/kg), which causes minimal change in blood pressure in normal mice, was infused for 14 days via osmotic minipump beginning 3 days after the 2nd Pg immunization. This protocol increased IFN-γ and TNF-α producing T cells by 10-fold, confirming induction of a TH1-like response. Pre-immunization with Pg + IL12 significantly increased the hypertension caused by angiotensin II, (146 ± 3 vs. 134 ± 2 mmHg in Pg lysate-treated vs vehicle injected controls; p < 0.01). Endothelium-dependent vasodilatation was minimally impaired by low dose angiotensin II alone (71 ± 18%) but was strikingly reduced when angiotensin II was given after immunization (15 ± 12%, p < 0.01). Pg immunization also increased peripheral T cell activation (CD69 13.5 ± 2% vs 8 ± 1% in Pg treated vs controls). Immunization increased T cell ICAM-1 receptor CD11b and CCR5 chemokine receptor, factors which could enhance vascular infiltration. In keeping with this, we found Pg lysate immunization markedly increased aortic T cell infiltration (77 ± 2 vs. 14 ± 4 X104 cells/aorta in Pg lysate treated vs control mice; p < 0.001). We conclude that enhancing the level of pre-existing activated T cells with an agent such as Porphyromonas gingivalis markedly predisposes to angiotensin II induced hypertension, T cell vascular infiltration and vascular dysfunction. These studies provide insight into mechanisms underlying the association between chronic infection and cardiovascular disease.