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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, METHODS, RESULTS. Meshes: Angiotensin II, Angiotensins, Animals, Apoptosis, Fibrosis, Heart, Mice, Mice, Transgenic, Mitogen-Activated Protein Kinases, Myocardium, Myocytes, Cardiac, NF-kappa B, Rats, Ubiquitin-Protein Ligases, Ventricular Remodeling.
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Does carboxyl terminus of heat shock protein 70-interacting protein inhibit angiotensin II-induced cardiac remodeling? Context: The 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. We 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. Seven 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.
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CHIP plays an important role in regulating Ang II-triggered hypertensive cardiac apoptosis, inflammation, and fibrosis. Final Decision: yes