| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1Department of Medical Pharmacology, School of Medicine, and 2Sarver Heart Center and Department of Surgery, College of Medicine, University of Arizona; 3Department of Health Promotion Sciences, Mel and Enid Zuckerman College of Public Health; and 4Department of Immunology, College of Medicine, University of Arizona, Tucson, Arizona
Submitted 25 January 2005 ; accepted in final form 7 April 2005
The induction of T helper (TH) lymphocytes by distinct TH ligands results in a differentiation to TH1/TH2 subsets based on their unique pattern of cytokine secretion and effector functions. We hypothesized that the relative proportion of TH1/TH2 directly relates to cardiac fibroblast (CF) function and thereby cardiac extracellular matrix (ECM) composition and cardiac diastolic function in the absence of injury or altered wall stress. We compared the effect of selective TH1 with TH2 inducers on cardiac gene expression, ECM composition, and diastolic function in C57BL/J mice. Twelve weeks after immune modulation, the left ventricular stiffness (
) was significantly increased in the TH1 group and decreased in the TH2 group (P < 0.01). The TH2 group also demonstrated significantly increased end-diastolic and end-systolic volumes (P < 0.01). Cardiac gene expression patterns for pro-matrix metalloproteinase (MMP)-9 and -13 were increased by greater than fivefold in the TH2 group and significantly decreased in the TH1 group (P < 0.05). The total cardiac collagen and cross-linked collagen were significantly increased in the TH1 group and decreased in the TH2 group (P < 0.01). Coculturing lymphocytes harvested from the treated mice with naive primary CF demonstrated a direct control of the lymphocytes on CF pro-collagen, pro-MMP gene expression, and MMP activity. These results suggest that the TH phenotype differentially affects diastolic function through modulating CF pro-collagen and pro-MMP gene expression, MMP activity, and cardiac collagen cross-linking, resulting in altered ECM composition. Thus modulation of TH lymphocyte function could promote adaptive remodeling in heart failure and postmyocardial infarction.
LP-BM5 retrovirus; T-helper cell; cardiac fibroblast; extracellular matrix; collagen types I and III; T helper 1; T helper 2; cross-linking; T-cell receptor peptide
This article has been cited by other articles:
|
|
 |
|
  J. S. Burchfield, M. Iwasaki, M. Koyanagi, C. Urbich, N. Rosenthal, A. M. Zeiher, and S. Dimmeler Interleukin-10 From Transplanted Bone Marrow Mononuclear Cells Contributes to Cardiac Protection After Myocardial Infarction Circ. Res., July 18, 2008; 103(2): 203 - 211. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. B. Stacy, Q. Yu, K. Horak, and D. F Larson Effect of angiotensin II on primary cardiac fibroblast matrix metalloproteinase activities Perfusion, January 1, 2007; 22(1): 51 - 55. [Abstract] [PDF]
|
|
|
|
 |
|
 Q. Yu, K. Horak, and D. F. Larson Role of T Lymphocytes in Hypertension-Induced Cardiac Extracellular Matrix Remodeling Hypertension, July 1, 2006; 48(1): 98 - 104. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. W. Booz Impact of T Lymphocytes on Cardiac Remodeling in Hypertension: More Questions Than Answers Hypertension, July 1, 2006; 48(1): 31 - 32. [Full Text] [PDF]
|
|
|
|
 |
|
 C. M. Alwardt, Q. Yu, H. L. Brooks, M. R. McReynolds, R. Vazquez, R. R. Watson, and D. F. Larson Comparative effects of dehydroepiandrosterone sulfate on ventricular diastolic function with young and aged female mice Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2006; 290(1): R251 - R256. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
