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

LYSOPHOSPHATIDIC ACID & TISSUE FACTOR IN ATHEROSCLEROSIS

Award Number: R01HL074341
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2004
PERIOD OF PERFORMANCE END DATE: 04/30/2008

Group Awards By:

View Award Description

LYSOPHOSPHATIDIC ACID & TISSUE FACTOR IN ATHEROSCLEROSIS - DESCRIPTION (provided by applicant): The long-term objective of this proposal is to explore the pathological role of LPA, a component of oxidized LDL, in atherosclerosis. The driving hypothesis of the proposal is that one of the mechanisms by which LPA, a component of oxLDL, contributes to atherosclerosis is via up-regulation of TF expression. This hypothesis is based on our novel findings that 1) lipid lysophosphatidic acid (LPA), which has recently been shown to accumulate in high concentrations in atherosclerotic lesions and identified as a component of oxLDL, markedly increases TF mRNA, TF protein production and TF activity in SMC; 2) LPA induced-TF gene expression requires the activation of a particular G-protein, MAPK, PKC, the novel protein kinase D (PKD), and ribosome S6 kinase (p90RSK); and 3) LPA induces TF mRNA expression in heart, kidney and aorta of the living animal. This hypothesis is also supported by the observations recently reported by others: 1) Tissue factor (TF) plays an important role in the development of atherosclerosis; 2) LPA accumulates in high concentrations in atherosclerotic lesions; and 3) LPA induces neointimal formation in rat aorta. This hypothesis is innovative because in the development of atherosclerosis, the role of this phospholipid LPA, which forms during oxidation of LDL and is secreted from activated platelets, is totally unknown. The goals of this proposal will be achieved through the following specific aims: Aim 1:To identify and determine the role of LPA receptor, specific G-protein, and the particular isoform of protein kinase C in LPA-stimulated TF expression, using specific antagonists of LPA receptors, affinity labeling, antisense oligonucleotides, as well as the dominant-negative approach. Aim 2: To explore the novel biological role of PKD and p90RSK in TF gene regulation, using selective inhibitors and the dominant-negative strategy. Aim 3: Using a well-established atherosclerotic model-ApoE knockout mouse, to determine i) the role of LPA in the development of atherosclerosis; ii) the role of TF in mediating the pathological effect of LPA in atherosclerotic lesion development in vivo. The information obtained from the proposed studies may lead to the identification of novel therapeutic targets for the prevention and treatment of atherosclerosis. The proposed studies would also contribute to the understanding of the cellular signaling pathway that mediates the biological effects of LPA, specifically the effects on gene regulation in general. The proposed studies would also provide novel insight into the biological and cellular function of PKD and p90RSK in the vascular wall.


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: 2007 ( Subtotal = $240,270 )
2007	2007	UNIVERSITY OF TENNESSEE	WEST CUMBERLAND AVENUE, SW	KNOXVILLE	TN	37916	KNOX	USA	Cardiovascular Diseases Research	000	4	4/26/2007	NON-COMPETING CONTINUATION	$240,270
														Subtotal = $240,270

Issue Date FY: 2006 ( Subtotal = $247,446 )
2006	2006	UNIVERSITY OF TENNESSEE	WEST CUMBERLAND AVENUE, SW	KNOXVILLE	TN	37916	KNOX	USA	Cardiovascular Diseases Research	000	3	5/18/2006	NON-COMPETING CONTINUATION	$247,446
														Subtotal = $247,446

Issue Date FY: 2005 ( Subtotal = $253,400 )
2005	2005	UNIVERSITY OF TENNESSEE	WEST CUMBERLAND AVENUE, SW	KNOXVILLE	TN	37916	KNOX	USA	Cardiovascular Diseases Research	000	2	5/4/2005	NON-COMPETING CONTINUATION	$253,400
														Subtotal = $253,400

Issue Date FY: 2004 ( Subtotal = $242,200 )
2004	2004	UNIVERSITY OF TENNESSEE	WEST CUMBERLAND AVENUE, SW	KNOXVILLE	TN	37916	KNOX	USA	Cardiovascular Diseases Research	000	1	5/12/2004	NEW	$242,200
														Subtotal = $242,200

Grand Total All Awards = $983,316

Top

All Categories

About

Search

Reports

Data Submission

Award Information

LYSOPHOSPHATIDIC ACID & TISSUE FACTOR IN ATHEROSCLEROSIS

Award Number: R01HL074341

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 07/01/2004

PERIOD OF PERFORMANCE END DATE: 04/30/2008

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer