This competitive renewal of our program project in Atherosclerosis continues to represent a mulitdisciplinary approach to understanding the intricate interrelationships of blood- and cell- derived factors with arterial tissue leading to the characteristic pathologic alterations found in atherosclerosis. The objectives of this proposal are to elucidate: 1) how modification of LDL, principally through oxidation, results in enhanced uptake by macrophages and cytotoxicity to proliferating smooth muscle cells and to endothelial cells; 2) how alterations in macrophage function due to interaction with proteins or lipoproteins leads to lipid loading, lipid removal or secretion of inflammatory products; 3) how growth factor production by endothelial cells and macrophages is regulated; 4) how the synthesis of collagen and other proteins by arterial smooth muscle cells in; and 5) how modification of the lipid composition of lipoproteins occurs in the plasma compartments. The rabbit and rat will be used as animal models. Endothelial and smooth muscle cells, derived from rabbit, bovine and human aortas, will be grown in tissue culture. Some techniques to be employed include cell binding of radiolabeled ligands, in vivo infusion of tracers, and colloidal gold-labeled ligands for ultrastructural studies. The research activities supported by Tissue Culture, Morphology, and Lipoprotein Core Facilities. This proposed program is expected to provide new and significant basic information leading to a clearer understanding of the sequence of events in atherogenesis.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL029582-07
Application #
3098093
Study Section
Heart, Lung, and Blood Research Review Committee B (HLBB)
Project Start
1983-07-01
Project End
1993-06-30
Budget Start
1989-07-01
Budget End
1990-06-30
Support Year
7
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Cleveland Clinic Lerner
Department
Type
DUNS #
017730458
City
Cleveland
State
OH
Country
United States
Zip Code
44195
Herjan, Tomasz; Hong, Lingzi; Bubenik, Jodi et al. (2018) IL-17-receptor-associated adaptor Act1 directly stabilizes mRNAs to mediate IL-17 inflammatory signaling. Nat Immunol 19:354-365
Robinet, Peggy; Milewicz, Dianna M; Cassis, Lisa A et al. (2018) Consideration of Sex Differences in Design and Reporting of Experimental Arterial Pathology Studies-Statement From ATVB Council. Arterioscler Thromb Vasc Biol 38:292-303
Zhang, Cun-Jin; Wang, Chenhui; Jiang, Meiling et al. (2018) Act1 is a negative regulator in T and B cells via direct inhibition of STAT3. Nat Commun 9:2745
Han, Juying; Enyindah-Asonye, Gospel; Lin, Feng et al. (2018) CD6 expression has no effect on atherosclerosis in apolipoprotein E-deficient mice. BMC Res Notes 11:229
Sarvestani, Samaneh K; Signs, Steven A; Lefebvre, Veronique et al. (2018) Cancer-predicting transcriptomic and epigenetic signatures revealed for ulcerative colitis in patient-derived epithelial organoids. Oncotarget 9:28717-28730
Arif, Abul; Yao, Peng; Terenzi, Fulvia et al. (2018) The GAIT translational control system. Wiley Interdiscip Rev RNA 9:
Hai, Qimin; Ritchey, Brian; Robinet, Peggy et al. (2018) Quantitative Trait Locus Mapping of Macrophage Cholesterol Metabolism and CRISPR/Cas9 Editing Implicate an ACAT1 Truncation as a Causal Modifier Variant. Arterioscler Thromb Vasc Biol 38:83-91
Eswarappa, Sandeep M; Potdar, Alka A; Sahoo, Sarthak et al. (2018) Metabolic origin of the fused aminoacyl-tRNA synthetase, glutamyl-prolyl-tRNA synthetase. J Biol Chem 293:19148-19156
Halawani, Dalia; Gogonea, Valentin; DiDonato, Joseph A et al. (2018) Structural control of caspase-generated glutamyl-tRNA synthetase by appended noncatalytic WHEP domains. J Biol Chem 293:8843-8860
Zhou, Hao; Bulek, Katarzyna; Li, Xiao et al. (2017) IRAK2 directs stimulus-dependent nuclear export of inflammatory mRNAs. Elife 6:

Showing the most recent 10 out of 276 publications