期刊
CARDIOVASCULAR TOXICOLOGY
卷 10, 期 3, 页码 190-198出版社
HUMANA PRESS INC
DOI: 10.1007/s12012-010-9078-7
关键词
Diastolic dysfunction; Lymphocytes; Lysyl oxidase; Cross-linked collagen
资金
- NCCAM [R21 AT004177]
- Wallace Research Foundation
- NIH [R01 HL079206]
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据