82 research outputs found
Cathepsin S Deficiency Results in Abnormal Accumulation of Autophagosomes in Macrophages and Enhances Ang II–Induced Cardiac Inflammation
BACKGROUND: Cathepsin S (Cat S) is overexpressed in human atherosclerotic and aneurysmal tissues and may contributes to degradation of extracellular matrix, especially elastin, in inflammatory diseases. We aimed to define the role of Cat S in cardiac inflammation and fibrosis induced by angiotensin II (Ang II) in mice. METHODS AND RESULTS: Cat S-knockout (Cat S(-/-)) and littermate wild-type (WT) C57BL/6J mice were infused continuously with Ang II (750 ng/kg/min) or saline for 7 days. Cat S(-/-) mice showed severe cardiac fibrosis, including elevated expression of collagen I and α-smooth muscle actin (α-SMA), as compared with WT mice. Moreover, macrophage infiltration and expression of inflammatory cytokines (tumor necrosis factor α, transforming growth factor β and interleukin 1β) were significantly greater in Cat S(-/-) than WT hearts. These Ang II-induced effects in Cat S(-/-) mouse hearts was associated with abnormal accumulation of autophagosomes and reduced clearance of damaged mitochondria, which led to increased levels of reactive oxygen species (ROS) and activation of nuclear factor-kappa B (NF-κB) in macrophages. CONCLUSION: Cat S in lysosomes is essential for mitophagy processing in macrophages, deficiency in Cat S can increase damaged mitochondria and elevate ROS levels and NF-κB activity in hypertensive mice, so it regulates cardiac inflammation and fibrosis
ChemInform Abstract: Regioselectivity in the Schmidt Reaction: First Synthesis of Pyrano[3,2-b]azepines.
ChemInform Abstract: Recent Applications of Alkene Metathesis for Fine Chemical and Supramolecular System Synthesis
ChemInform Abstract: Ruthenium(II) Acetate Catalyst for Direct Functionalization of sp 2
ChemInform Abstract: The Synthesis of 12-Membered Macrocycles Containing a C1-C8 Alkene Unit via Ring-Closing Metathesis.
ChemInform Abstract: 4-Acylhydrazinomethylene-2-phenyloxazol-5(4H)-ones as Acylating Agents: Synthesis of Salicylanilides and 1,2,4-Triazolo[4,3-b]pyridazines.
Ammonium Cerium(IV) Nitrate as an Efficient Oxidizing Agent for Fused 1,4-Dihydropyridazine Derivatives and Hydrazides.
Pyran-2-ones as Synthons for Pyridazine-3-carboxylic Derivatives. Oxidation of Nitrogen-Rich Compounds.
ChemInform Abstract: Ring Transformations of 2H-Pyran-2-ones and Fused Pyran-2-ones with Nucleophilic Reagents
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