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Insights Nutr Metab 2017
Volume 1 Issue 3
Nutrition World 2017
Page 64
September 11-12, 2017 Edinburgh, Scotland
15
th
World Congress on
Advances in Nutrition, Food Science & Technology
TRPV4 calcium-permeable channel is a
novel regulator of oxidized LDL-induced
Macrophage foam cell formation
Shaik O. Rahaman
University of Maryland, USA
C
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: i) genetic
ablation of TRPV4 or pharmacologic inhibition of TRPV4
activity by a specific antagonist blocked oxLDL-induced
macrophage foam cell formation, and ii) TRPV4 deficiency
prevented matrix stiffness or scratch-induced exacerbation
of oxLDL-induced foam cell formation. Mechanistically,
we found that: i) plasma membrane localization of TRPV4
was sensitized to the increasing level of matrix stiffness,
and ii) 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.
srahaman@umd.eduInsights Nutr Metab 2017