Grant: Project Grant
McMaster University
$692,326.00
Retention of PCSK9 in the endoplasmic reticulum acts as a co-chaperone to protect against liver injury/dysfunction
FY 2019-20
Summary
This study examines the role of PCSK9 retention on liver function/injury, including the development of hepatic steatosis. PCSK9 can regulate the development of cardiovascular disease (CVD). Individuals that do not produce enough PCSK9 from the liver are protected against CVD. PCSK9 retention in the liver would also lead to reduced blood levels and the risk of CVD. We have now discovered that PCSK9 that is not secreted in the blood but remains in the liver protects and liver injury/dysfunction. The PCSK9 that is retained in the liver acts to increase important chaperone proteins, termed GRP78 and GRP94, that block the development of liver disease. These studies will allow us to develop new medicines that increase the levels of PCSK9 in the liver that would not only reduce CVD but protect against liver disease and its complications.
Department
Program
Project Grant
Recipient
Location
Ontario, Canada
Recipient Type
Academia
Type
Grant
Source
CIHR Funding Decisions Database
As published
Id
418859
Name
Austin Richard C
Region
Ontario
Country
Canada
Orgtype
Institution Paid; Research Institution
Instname2
Nutrition, Metabolism and Diabetes
Theme2
Biomedical
Prcname2
Diabetes, Obesity, Lipid & Lipoprotein Disorders
Projecttitle
Retention of PCSK9 in the endoplasmic reticulum acts as a co-chaperone to protect against liver injury/dysfunction
Programtype2
Operating Grants
Orgnameinp2
McMaster University
Cihramount2
$692,326
Cihrequipment2
$0
Programname2
Project Grant
Keyworddelim
Cardiovascular Disease; Er Chaperones; Er Stress; Grp78 And Grp94; Hepatic Steatosis; Hepatocytes; Liver Dysfunction/Injury; Pcsk9
Abstract
This study examines the role of PCSK9 retention on liver function/injury, including the development of hepatic steatosis. PCSK9 can regulate the development of cardiovascular disease (CVD). Individuals that do not produce enough PCSK9 from the liver are protected against CVD. PCSK9 retention in the liver would also lead to reduced blood levels and the risk of CVD. We have now discovered that PCSK9 that is not secreted in the blood but remains in the liver protects and liver injury/dysfunction. The PCSK9 that is retained in the liver acts to increase important chaperone proteins, termed GRP78 and GRP94, that block the development of liver disease. These studies will allow us to develop new medicines that increase the levels of PCSK9 in the liver that would not only reduce CVD but protect against liver disease and its complications.
Competitiondate
202003
Approvedterm2
5 yrs 0 mth
Pinamesdelim
Austin, Richard C
Approvedterm
5 ans 0 mois
Cihrcontribution2
~ $692,326~ $0~
