Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

The role of PAR2 and HuR in programming atherosclerotic vascular smooth muscle cells

Award Number: F31HL170534
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 09/30/2023
PERIOD OF PERFORMANCE END DATE: 01/10/2025

Group Awards By:

View Award Description

The role of PAR2 and HuR in programming atherosclerotic vascular smooth muscle cells - PROJECT SUMMARY/ABSTRACT Coronary artery disease (CAD), the result of atherosclerosis formation, is the leading cause of death globally resulting in approximately 679,000 annual deaths or the equivalent to every one in five deaths occurring in the United States. This number is expected to increase as comorbidities of CAD diagnosed in patients continues to rise. Currently, statins, which lowers the amount of circulating lipids, are the gold standard of preventing CAD in patients with a concomitant diet and exercise regimen. After decades of steadily improving mortality rates, overall trends have begun to plateau and current medications provide only modest absolute incremental benefits from atherosclerotic plaque rupture and resultant myocardial infarction, stoke, and heart failure. Our laboratory has previously demonstrated the G-protein coupled receptor, PAR2, is augmented in both murine and human atherosclerotic plaques. Moreover, studies have demonstrated increased Human Antigen R (HuR) expression at sites of vessel injury, with the potential to bind and stabilize PAR2 mRNA in these inflammatory conditions. Though we know PAR2 contributes to the formation of atherosclerosis, the mechanism(s) in which PAR2 mediates atherosclerosis formation and the role of HuR in atherosclerosis are still unknown. Understanding the molecular mechanisms in which PAR2 and HuR contributes to the progression of atherosclerosis could give new insight into potential targets of therapeutics that could improve the outcomes of CAD patients and put a halt to the diminishing returns of old therapeutics. The primary goal of this proposal is to investigate the mechanisms by which PAR2 and HuR interact and their contributions, both independently and dependently, to atherosclerosis development. Using data previously collected in our lab, we know that the contributions of PAR2 in atherosclerosis derive from a non-hematopoietic cell type, such as vascular smooth muscle cells (VSMCs). Thus, we hypothesize that activation of PAR2 in VSMCs relocates HuR to the cytosol where it binds and stabilizes Par2 mRNA, upregulating PAR2 expression and further progressing atherosclerosis. This hypothesis will be using two specific aims and several mouse models that consist of PAR2 and HuR genetic mutants, specifically in VSMCs (aim 1 and aim 2 respectively). We will also use a variety of in vitro experiments to observe HuR binding PAR2 mRNA (aim 2) as well as investigate the role of PAR2 in VSMC dedifferentiation (aim 1), which recent literature has shown the contributions of VSMC dedifferentiation to the progression of atherosclerosis. The long-term objective of this study is to further elucidate the role of PAR2 in atherosclerosis and, if successful, will advance our knowledge of the development and progression of this disease. These results may also positively impact the field and give sight to potential targets to develop new therapies for CAD patients.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = -$4,662 )
2026	2024	CINCINNATI UNIV OF	2600 CLIFTON AVE	CINCINNATI	OH	45220	HAMILTON	USA	Cardiovascular Diseases Research	000	2	3/24/2026	NON-COMPETING CONTINUATION	-$4,662
														Subtotal = -$4,662

Issue Date FY: 2025 ( Subtotal = -$27,073 )
2025	2024	CINCINNATI UNIV OF	2600 CLIFTON AVE	CINCINNATI	OH	45220	HAMILTON	USA	Cardiovascular Diseases Research	000	2	3/31/2025	NON-COMPETING CONTINUATION	-$27,073
														Subtotal = -$27,073

Issue Date FY: 2024 ( Subtotal = $37,445 )
2024	2024	CINCINNATI UNIV OF	2600 CLIFTON AVE	CINCINNATI	OH	45220	HAMILTON	USA	Cardiovascular Diseases Research	000	2	8/9/2024	NON-COMPETING CONTINUATION	$37,445
														Subtotal = $37,445

Issue Date FY: 2023 ( Subtotal = $36,165 )
2023	2023	UNIVERSITY OF CINCINNATI	2600 CLIFTON AVE	CINCINNATI	OH	45220	HAMILTON	USA	Cardiovascular Diseases Research	000	1	8/19/2023	NEW	$36,165
														Subtotal = $36,165

Grand Total All Awards = $41,875

Top

All Categories

About

Search

Reports

Data Submission

Award Information

The role of PAR2 and HuR in programming atherosclerotic vascular smooth muscle cells

Award Number: F31HL170534

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 09/30/2023

PERIOD OF PERFORMANCE END DATE: 01/10/2025

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer