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Virology Research Journal

Volume 1 Issue 4

Vaccines World 2017

Notes:

Page 43

November 09-10, 2017 Vienna, Austria

World Congress and Exhibition on

VACCINES, VACCINATION & IMMUNIZATION

TRPV4 calcium-permeable channel is a

novel regulator of oxidized LDL-induced

macrophage foam cell formation

Shaik O Rahaman

University of Maryland, USA

ardiovascular disease is the number one cause of death

in developed world, and atherosclerosis, a chronic

inflammatory arterial disease, is the most dominant

underlying pathology. Macrophages are thought to orchestrate

atherosclerosis by generating lipid-laden foam cells and by

secreting inflammatory mediators. Emerging data support a

role for a mechanical factor, e.g., matrix stiffness, in regulation

of macrophage function and atherogenesis. We have obtained

evidence that TRPV4, an ion channel in the transient receptor

potential vanilloid family and a known mechanosensor, is the

likely mediator of oxidized low-density lipoprotein (oxLDL)-

dependent macrophage foam cell formation, a critical process

in atherogenesis. Specifically, we found that genetic ablation

of TRPV4 or pharmacologic inhibition of TRPV4 activity by

a specific antagonist blocked oxLDL-induced macrophage

foam cell formation, and TRPV4 deficiency prevented

matrix stiffness or scratch-induced exacerbation of oxLDL-

induced foam cell formation. Mechanistically, we found that

plasma membrane localization of TRPV4 was sensitized to

the increasing level of matrix stiffness, and TRPV4 activity

regulated oxLDL uptake but not its internalization in

macrophages. Altogether, these findings identify a novel role

for TRPV4 in regulating macrophage foam cell formation by

modulating uptake of oxLDL.

Virol Res J 2017, 1:4