miR146a is a microRNA that regulates inflammation and is being investigated for its potential role in lipids metabolism and atherosclerosis. PCSK9 gain of function mutations cause high cholesterol by reducing LDL receptors, resulting in increased total cholesterol levels. The document discusses exploring the role of miR146a in the mechanism by which PCSK9 causes hypercholesterolemia.
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1. miR146a is a microRNA
Well known to regulate
Inflammation
Injecting
PCSK9 AAV vector to
mimic
high cholesterol
Where to go:
miR146a and lipids metabolism
Effect on atherosclerosis
PCSK9 gain of function
mutation results in increased
cholesterol by reducing LDL
receptors
TotalCholesterol(mg/dl)
0
50
100
150
200
250
WT
KO
Plasma Cholesterol
PCSK9 mechanism of action on hypercholesterolemia:
possible role of miR146a
Shayan Mohamamdmoradi Dr. Subramanian Laboratory
Investigating
role of miR146a
*
Baseline Week 4
*P<0.05 WT vs KO
Editor's Notes
PCSK9 is an enzyme that its GOF mutation will result in increased cholesterol.Also, miR146a is a microRNA that seems to play a role in cholesterol efflux.
In this project, we investigated the role of miR146a in PCSK9 induced hypercholesterolemia. Using miR146a WT and KO mice, miR146a KO mice showed a significant reduction of plasma total cholesterol, inducing HDL-C levels irrespective to comparable PCSK9 levels. Our current focus is to understand the mechanism i.e. identifying its targets by which miR146a regulates HDL-C and its effect on atherosclerosis development.