作者
Joel Schilling, Ling Lai, Nandakumar Sambandam, Courtney E Dey, Teresa C Leone, Daniel P Kelly
发表日期
2011/7
期刊
Circulation: Heart Failure
卷号
4
期号
4
页码范围
474-482
出版商
Lippincott Williams & Wilkins
简介
Background
Currently, there are no specific therapies available to treat cardiac dysfunction caused by sepsis and other chronic inflammatory conditions. Activation of toll-like receptor 4 (TLR4) by lipopolysaccharide (LPS) is an early event in Gram-negative bacterial sepsis, triggering a robust inflammatory response and changes in metabolism. Peroxisome proliferator–activated receptor-γ coactivator-1 (PGC-1) α and β serve as critical physiological regulators of energy metabolic gene expression in heart.
Methods and Results
Injection of mice with LPS triggered a myocardial fuel switch similar to that of the failing heart: reduced mitochondrial substrate flux and myocyte lipid accumulation. The LPS-induced metabolic changes were associated with diminished ventricular function and suppression of the genes encoding PGC-1α and β, known transcriptional regulators of mitochondrial function. This cascade of events …
学术搜索中的文章
J Schilling, L Lai, N Sambandam, CE Dey, TC Leone… - Circulation: Heart Failure, 2011