Abstract
Background and PurposeEmerging evidence indicates that hypertension is mediated by immune mechanisms. We hypothesized that exposure to Porphyromonas gingivalis antigens, commonly encountered in periodontal disease, can enhance immune activation in hypertension and exacerbate the elevation in BP, vascular inflammation and vascular dysfunction.Experimental ApproachTh1 immune responses were elicited through immunizations using P. gingivalis lysate antigens (10 μg) conjugated with aluminium oxide (50 μg) and IL‐12 (1 μg). The hypertension and vascular endothelial dysfunction evoked by subpressor doses of angiotensin II (0.25 mg·kg−1·day−1) were studied, and vascular inflammation was quantified by flow cytometry and real‐time PCR.Key ResultsSystemic T‐cell activation, a characteristic of hypertension, was exacerbated by P. gingivalis antigen stimulation. This translated into increased aortic vascular inflammation with enhanced leukocyte, in particular, T‐cell and macrophage infiltration. The expression of the Th1 cytokines, IFN‐γ and TNF‐α, and the transcription factor, TBX21, was increased in aortas of P. gingivalis/IL‐12/aluminium oxide‐immunized mice, while IL‐4 and TGF‐β were unchanged. These immune changes in mice with induced T‐helper‐type 1 immune responses were associated with an enhanced elevation of BP and endothelial dysfunction compared with control mice in response to 2 week infusion of a subpressor dose of angiotensin II.Conclusions and ImplicationsThese results support the concept that Th1 immune responses induced by bacterial antigens such as P. gingivalis can increase sensitivity to subpressor pro‐hypertensive insults such as low‐dose angiotensin II, thus providing a mechanistic link between chronic infection, such as periodontitis, and hypertension.Linked ArticlesThis article is part of a themed section on Immune Targets in Hypertension. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.12/issuetoc
Highlights
It has become increasingly evident that the immune system plays a critical role in the development of hypertension and its attendant end-organ damage
In 2007, we reported that RAG1-deficient mice, which lack B and T cells have blunted hypertensive responses following the infusion of angiotensin II (Ang II)
Flow cytometric analysis of single-cell suspensions of aortas obtained from mice after 14 days of Ang II low-dose infusion revealed that total aortic leukocytes, as reflected by CD45positive cells, were significantly increased in mice immunized with P. gingivalis compared with mice that received alum alone (Figure 2A)
Summary
It has become increasingly evident that the immune system plays a critical role in the development of hypertension and its attendant end-organ damage. Both adaptive and innate immune responses have been implicated in the pathogenesis of primary and secondary forms of hypertension (Harrison et al, 2011). The development of vascular dysfunction in these mice is attenuated and their vascular production of free radicals in response to Ang II infusion is reduced (Guzik et al, 2007). We hypothesized that exposure to Porphyromonas gingivalis antigens, commonly encountered in periodontal disease, can enhance immune activation in hypertension and exacerbate the elevation in BP, vascular inflammation and vascular dysfunction. The hypertension and vascular endothelial dysfunction evoked by subpressor doses of angiotensin II (0.25 mg·kgÀ1·dayÀ1) were studied, and vascular inflammation was quantified by flow cytometry and real-time PCR
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