Abstract

Apoptosis occurs in advanced human and experimental atherosclerosis, but little is known about the role of apoptosis in determination of the cellularity of arteries with early atherosclerotic lesion or fatty streaks. This application proposes that apoptosis represents a mechanism for eliminating cells from the intima, and that vascular cells undergo apoptosis following exposure to cytokines produced by T cells and macrophages which are also present in the lesion. It is further proposed that this is mediated by the Fas death signaling pathway and the ICE protease family.
Specific Aim 1 will examine the balance between apoptosis and cell proliferation in arterial samples collected in the PDAY program by immunohistochemistry.
Specific Aim 2 will examine expression of Fas, Fas ligand, and ICE-related proteases in smooth muscle cells undergoing apoptosis in atherosclerotic lesions and in cultured cells.
Specific Aim 3 will examine the function of fragments of actin an gelsolin in mediating apoptosis. Arteries from mice deficient in expression of functional Fas (MRC/lpr/lpr) or gelsolin will be examined.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL059249-05
Application #
6537353
Study Section
Pathology A Study Section (PTHA)
Program Officer
Rabadan-Diehl, Cristina
Project Start
1998-04-01
Project End
2004-03-31
Budget Start
2002-04-01
Budget End
2004-03-31
Support Year
5
Fiscal Year
2002
Total Cost
$112,781
Indirect Cost

  Institution

Name
University of Texas Health Science Center Houston
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
City
Houston
State
TX
Country
United States
Zip Code
77225

  Publications

Rosales, Corina; Tang, Daming; Geng, Yong-Jian (2015) CD1d serves as a surface receptor for oxidized cholesterol induction of peroxisome proliferator-activated receptor-?. Atherosclerosis 239:224-31
Gao, Song; Wassler, Michael; Zhang, Lulu et al. (2014) MicroRNA-133a regulates insulin-like growth factor-1 receptor expression and vascular smooth muscle cell proliferation in murine atherosclerosis. Atherosclerosis 232:171-9
Madonna, Rosalinda; Geng, Yong-Jian; Bolli, Roberto et al. (2014) Co-activation of nuclear factor-?B and myocardin/serum response factor conveys the hypertrophy signal of high insulin levels in cardiac myoblasts. J Biol Chem 289:19585-98
Madonna, R; Wu, H; Shelat, H et al. (2013) CD1d-associated expression of NF-kB and cardiac dysfunction in diabetic and obese mice. Int J Immunopathol Pharmacol 26:59-73
Madonna, Rosalinda; Wu, Danli; Wassler, Michael et al. (2013) Myocardin-A enhances expression of promyogenic genes without depressing telomerase activity in adipose tissue-derived mesenchymal stem cells. Int J Cardiol 167:2912-21
Madonna, R; Jiang, J; Geng, Y-J (2012) Attenuated expression of gelsolin in association with induction of aquaporin-1 and nitric oxide synthase in dysfunctional hearts of aging mice exposed to endotoxin. Int J Immunopathol Pharmacol 25:911-22
Geng, Yong-Jian; Jonasson, Lena (2012) Linking immunity to atherosclerosis: implications for vascular pharmacology--a tribute to Göran K. Hansson. Vascul Pharmacol 56:29-33
Madonna, Rosalinda; De Caterina, Raffaele; Willerson, James T et al. (2011) Biologic function and clinical potential of telomerase and associated proteins in cardiovascular tissue repair and regeneration. Eur Heart J 32:1190-6
Madonna, Rosalinda; Salerni, Sara; Schiavone, Deborah et al. (2011) Omega-3 fatty acids attenuate constitutive and insulin-induced CD36 expression through a suppression of PPAR ?/? activity in microvascular endothelial cells. Thromb Haemost 106:500-10
Madonna, Rosalinda; Shelat, Harnath; Xue, Qun et al. (2009) Erythropoietin protects myocardin-expressing cardiac stem cells against cytotoxicity of tumor necrosis factor-alpha. Exp Cell Res 315:2921-8

Showing the most recent 10 out of 22 publications