TRPV4 regulates P. gingivalis lipopolysaccharide‐induced exacerbation of oxidized LDL‐mediated foam cell formation

Abstract

P. gingivalis, a predominant causative agent of periodontitis, has been linked to lipid‐laden macrophage foam cell formation, a critical process in atherogenesis. Emerging data support a role for both a biochemical factor, e.g., lipopolysaccharides (LPS), and a mechanical factor, e.g., matrix stiffness, in regulation of macrophage function and atherogenesis. We have obtained evidence that TRPV4, a mechanosensitive channel of the transient receptor potential vanilloid family, is the likely mediator of P. gingivalis lipopolysaccharide (PgLPS)‐induced exacerbation of oxidized low‐density lipoprotein (oxLDL)‐mediated macrophage foam cell formation. Specifically, we found that: i) genetic deletion of TRPV4 or antagonism of its function by a chemical inhibitor blocked PgLPS‐induced exacerbation of oxLDL‐induced macrophage foam cell formation; ii) macrophage TRPV4 activity was increased in response to both PgLPS and pathophysiological range matrix stiffness, and iii) TRPV4 deficiency blocked PgLPS‐induced exacerbation of matrix stiffness‐induced macrophage foam cell formation. Mechanistically, we show that TRPV4 regulates PgLPS‐induced oxLDL uptake but not its cell surface binding in macrophages. Altogether, these findings identify a critical role for TRPV4 in regulating PgLPS‐induced exacerbation of macrophage foam cell formation by modulating uptake of oxLDL.Support or Funding InformationAHA (13SDG17310007), Startup grant from University of Maryland, NIH (1R01EB024556‐01), and NSF (CMMI‐1662776) grants to Shaik RahamanThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.