title: T lymphocyte regulation of lysyl oxidase in diet-induced cardiac fibrosis.
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.
authors.affiliation: Sarver Heart Center, College of Medicine, The University of Arizona, Tucson, AZ 85724, USA.
authors.forename: Sherma
authors.initials: S
authors.lastname: Zibadi
authors.forename: Randy
authors.initials: R
authors.lastname: Vazquez
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Larson
authors.forename: Ronald R
authors.initials: RR
authors.lastname: Watson
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003094:Collagen / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004032:Diet / Q000009:adverse effects*; D004797:Enzyme-Linked Immunosorbent Assay; D005109:Extracellular Matrix / Q000187:drug effects / Q000648:ultrastructure; D005260:Female; D005355:Fibrosis; D015870:Gene Expression / Q000187:drug effects; D006331:Heart Diseases / Q000201:enzymology* / Q000209:etiology* / Q000473:pathology; D006439:Hemodynamics / Q000502:physiology; D020782:Matrix Metalloproteinases / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000473:pathology; D008249:Protein-Lysine 6-Oxidase / Q000378:metabolism*; D012313:RNA / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000502:physiology*
chemical_list: D016207:Cytokines; D012313:RNA; D003094:Collagen; D008249:Protein-Lysine 6-Oxidase; D020782:Matrix Metalloproteinases