Porphyromonas gingivalis (P.g), a major causative agent of periodontitis, has been linked to atherosclerosis, a chronic inflammatory vascular disease. Recent studies have suggested a link between periodontitis and arterial stiffness, a risk factor for atherosclerosis. However, the mechanisms by which P.g infection contributes to atherogenesis remain elusive. The formation of lipid‐laden macrophage “foam cells” is critically important to development and progression of atherosclerosis. We have obtained evidence that TRPV 4 (transient receptor potential channel of the vanilloid subfamily 4), a mechanosensitive channel, is a regulator of macrophage foam cell formation both in response to P.g‐derived lipopolysaccharide (Pg LPS ) or to an increase in matrix stiffness. Importantly, we found that TRPV 4 activity (Ca 2+ influx) was increased in response to Pg LPS . Genetic deletion or chemical antagonism of TRPV 4 channels blocked Pg LPS ‐triggered exacerbation of oxidized LDL (ox LDL )‐mediated foam cell formation. Mechanistically, we found that (1) T RPV 4 regulated ox LDL uptake but not its cell surface binding in macrophages; (2) reduced foam cell formation in TRPV 4 null cells was independent of expression of CD 36, a predominant receptor for ox LDL , and (3) co‐localization of TRPV 4 and CD 36 on the macrophage plasma membrane was sensitive to the increased level of matrix stiffness occurring in the presence of Pg LPS . Altogether, our results suggest that TRPV 4 channels play an essential role in P.g‐induced exacerbation of macrophage foam cell generation through a mechanism that modulates uptake of ox LDL .

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with this disease include paleness, a poor appetite, failure to thrive, jaundice, enlarged organs, frequent infections [1].

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