Abstract

The overall goal of this proposal is to examine the mechanisms by which triglyceride-rich lipoproteins (TGRL), and a major TGRL apoprotein (apoE), interact with the artery wall. Our preliminary data suggest that arterial endothelium must be injured before significant TGRL can enter the artery wall, lipolysis of TGRL may injure endothelium and apoE limits TGRL penetration into the artery wall. By using a recently developed mouse perfusion artery model, we propose to examine how TGRL interacts with the artery wall by determining: (1) The mechanisms of accumulation of TGRL on the endothelial cell luminal surface and in the artery wall. (2) The actions of lipolysis of TGRL on endothelial cell permeability properties and low-density lipoprotein (LDL) trafficking in the artery wall. (3) How apoE-associated lipoproteins bind to endothelium and if apoE isoforms (apoE3 versus apoE4) differ in their interactions with the arterial wall. Completion of these aims will greatly increase the knowledge base with regard to the effects of TGRL on vascular disease, potentially fundamentally change in the way we think about vascular disease and set the stage for the development of therapeutic strategies aimed at prevention of TGRL-induced arterial disease. ? ?

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL055667-11
Application #
7102833
Study Section
Cardiovascular and Renal Study Section (CVB)
Program Officer
Wassef, Momtaz K
Project Start
1996-08-01
Project End
2007-07-31
Budget Start
2006-08-01
Budget End
2007-07-31
Support Year
11
Fiscal Year
2006
Total Cost
$287,699
Indirect Cost

  Institution

Name
University of California Davis
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
047120084
City
Davis
State
CA
Country
United States
Zip Code
95618

  Publications

Aung, Hnin Hnin; Altman, Robin; Nyunt, Tun et al. (2016) Lipotoxic brain microvascular injury is mediated by activating transcription factor 3-dependent inflammatory and oxidative stress pathways. J Lipid Res 57:955-68
Eiselein, Larissa; Nyunt, Tun; Lamé, Michael W et al. (2015) TGRL Lipolysis Products Induce Stress Protein ATF3 via the TGF-? Receptor Pathway in Human Aortic Endothelial Cells. PLoS One 10:e0145523
Aung, Hnin H; Tsoukalas, Athanasios; Rutledge, John C et al. (2014) A systems biology analysis of brain microvascular endothelial cell lipotoxicity. BMC Syst Biol 8:80
Yahiatène, Idir; Aung, Hnin H; Wilson, Dennis W et al. (2014) Single-molecule quantification of lipotoxic expression of activating transcription factor 3. Phys Chem Chem Phys 16:21595-21601
den Hartigh, Laura J; Altman, Robin; Norman, Jennifer E et al. (2014) Postprandial VLDL lipolysis products increase monocyte adhesion and lipid droplet formation via activation of ERK2 and NF?B. Am J Physiol Heart Circ Physiol 306:H109-20
Armstrong, Ehrin J; Rutledge, John C; Rogers, Jason H (2013) Coronary artery revascularization in patients with diabetes mellitus. Circulation 128:1675-85
Aung, Hnin H; Lame, Michael W; Gohil, Kishorchandra et al. (2013) Induction of ATF3 gene network by triglyceride-rich lipoprotein lipolysis products increases vascular apoptosis and inflammation. Arterioscler Thromb Vasc Biol 33:2088-96
den Hartigh, Laura J; Altman, Robin; Hutchinson, Romobia et al. (2012) Postprandial apoE isoform and conformational changes associated with VLDL lipolysis products modulate monocyte inflammation. PLoS One 7:e50513
Ng, Kit Fai; Aung, Hnin Hnin; Rutledge, John C (2011) Role of triglyceride-rich lipoproteins in renal injury. Contrib Nephrol 170:165-71
Schie, Iwan W; Wu, Jian; Weeks, Tyler et al. (2011) Label-free imaging and analysis of the effects of lipolysis products on primary hepatocytes. J Biophotonics 4:425-34

Showing the most recent 10 out of 54 publications