Cardiovascular Toxicology

, Volume 10, Issue 3, pp 190–198

T Lymphocyte Regulation of Lysyl Oxidase in Diet-Induced Cardiac Fibrosis

Authors

  • Sherma Zibadi
    • Sarver Heart Center, College of MedicineThe University of Arizona
    • Division of Health Promotion Sciences, Mel and Enid Zuckerman Arizona College of Public HealthThe University of Arizona
  • Randy Vazquez
    • Sarver Heart Center, College of MedicineThe University of Arizona
    • Department of Nutritional SciencesThe University of Arizona
  • Douglas F. Larson
    • Sarver Heart Center, College of MedicineThe University of Arizona
    • Sarver Heart Center, College of MedicineThe University of Arizona
    • Division of Health Promotion Sciences, Mel and Enid Zuckerman Arizona College of Public HealthThe University of Arizona
Article

DOI: 10.1007/s12012-010-9078-7

Cite this article as:
Zibadi, S., Vazquez, R., Larson, D.F. et al. Cardiovasc Toxicol (2010) 10: 190. doi:10.1007/s12012-010-9078-7

Abstract

Left ventricular diastolic dysfunction is an important predictor of prognosis and mortality of heart failure. Increased left ventricular stiffness can be associated with excessive myocardial fibrosis and increased cross-linked collagen by the enzyme lysyl oxidase (LOX). These cardiac extracellular matrix (ECM) remodeling processes are affected by T-lymphocyte function and phenotype. We sought to examine the role of T lymphocytes in myocardial LOX regulation in diet-induced fibrotic hearts. Female SCID mice, devoid of functional T lymphocytes, and wild-type (WT) C57BL/6 were treated with a high-fat high-simple carbohydrate (HFHSC) diet for 12 months. HFHSC-fed WT mice demonstrated a significant increase in the catalytic activity of myocardial LOX compared with respective controls. These changes coincided with a marked increase in ECM collagen cross-linking and impaired diastolic filling pattern. However, induction of LOX was minimal in the SCID mice compared with the WT group. Correspondingly fibrillar cross-linked collagen concentrations and diastolic dysfunction were less prominent in the SCID mice compared with the WT group. Our results suggest a role for T lymphocytes in this dietary induction of diastolic dysfunction through modulation of LOX-dependent collagen maturation.

Keywords

Diastolic dysfunction Lymphocytes Lysyl oxidase Cross-linked collagen

Copyright information

© Springer Science+Business Media, LLC 2010