We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Carboxyl Terminus of Heat Shock Protein 70-Interacting Protein Inhibits Angiotensin II-Induced Cardiac Remodeling.
- Authors
Yang, Kun; Zhang, Tian-Peng; Tian, Cui; Jia, Li-xin; Du, Jie; Li, Hui-Hua
- Abstract
BackgroundThe carboxyl terminus of heat shock protein 70-interacting protein (CHIP), an E3 ligase/chaperone, was found to protect cardiomyocytes against apoptosis induced by ischemic injury; however, the functional role of CHIP in remodeling induced by angiotensin II (Ang II) remains unclear.MethodsWe generated CHIP-overexpressed transgenic (TG) mice infused with Ang II (1,500 ng/kg/min) or saline for days or small interfering RNA (siRNA) knockdown of neonatal rat cardiomyocytes. Heart sections were stained with hematoxylin and eosin, Masson trichrome, TdT-mediated dUTP nick-end labeling (TUNEL) staining, and immunohistochemistry, and the levels of nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPK) were measured by western blot analysis.ResultsSeven days after Ang II infusion, cardiac-specific overexpression of CHIP significantly enhanced cardiac contractile performance in mice and attenuated cardiac apoptosis, fibrosis, and inflammation: the number of TUNEL-positive cells, fibrotic areas, macrophage infiltration, and the expression of interleukin-1β (IL-1β), IL-6, monocyte chemoattractant protein-1 (MCP-1) and intercellular adhesion molecule-1 (ICAM-1) in heart tissues were decreased as compared with wild-type (WT) mice (all P < 0.05). In contrast, CHIP siRNA knockdown markedly increased Ang II-induced apoptosis and the expression of proinflammatory cytokines, as compared with siRNA control. The mechanisms underlying these beneficial actions were associated with CHIP-mediated inhibition of NF-κB and MAPK (p38 and JNK) pathways.ConclusionsCHIP plays an important role in regulating Ang II-triggered hypertensive cardiac apoptosis, inflammation, and fibrosis.American Journal of Hypertension 2012; doi:10.1038/ajh.2012.74
- Subjects
HEAT shock proteins; ANGIOTENSIN II; VENTRICULAR remodeling; APOPTOSIS; BLOOD pressure; HEART fibrosis; HYPERTENSION; MITOGEN-activated protein kinase kinase
- Publication
American Journal of Hypertension, 2012, Vol 25, Issue 9, p994
- ISSN
0895-7061
- Publication type
Article
- DOI
10.1038/ajh.2012.74