A role for T lymphocytes in mediating cardiac diastolic function
| Autor: | Qianli Yu, John J. Marchalonis, Ronald R. Watson, Douglas F. Larson |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Physiology
Receptors Antigen T-Cell alpha-beta Biology Extracellular matrix Mice Th2 Cells Diastole Physiology (medical) medicine Animals Diastolic function RNA Messenger Protein Precursors Fibroblast chemistry.chemical_classification Myocardium Genetic Variation Heart T helper cell T lymphocyte Fibroblasts Th1 Cells Coculture Techniques Matrix Metalloproteinases Peptide Fragments Extracellular Matrix Leukemia Virus Murine Mice Inbred C57BL medicine.anatomical_structure chemistry Immune System Immunology Circulatory system Female Cytokine secretion Cardiology and Cardiovascular Medicine Glycoprotein Procollagen Retroviridae Infections |
| Zdroj: | American Journal of Physiology-Heart and Circulatory Physiology. 289:H643-H651 |
| ISSN: | 1522-1539 0363-6135 |
| DOI: | 10.1152/ajpheart.00073.2005 |
| Popis: | 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 (β) 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. |
| Databáze: | OpenAIRE |
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