Human mast cell neutral proteases generate modified LDL particles with increased proteoglycan binding

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Maaninka , K , Nguyen , S D , Mäyränpää , M I , Plihtari , R , Rajamäki , K , Lindsberg , P J , Kovanen , P T & Öörni , K 2018 , ' Human mast cell neutral proteases generate modified LDL particles with increased proteoglycan binding ' , Atherosclerosis , vol. 275 , pp. 390-399 . https://doi.org/10.1016/j.atherosclerosis.2018.04.016

Title: Human mast cell neutral proteases generate modified LDL particles with increased proteoglycan binding
Author: Maaninka, Katariina; Nguyen, Su Duy; Mäyränpää, Mikko I.; Plihtari, Riia; Rajamäki, Kristiina; Lindsberg, Perttu J.; Kovanen, Petri T.; Öörni, Katariina
Contributor: University of Helsinki, Wihuri Research Institute
University of Helsinki, Medicum
University of Helsinki, Clinicum
University of Helsinki, Clinicum
University of Helsinki, Wihuri Research Institute
Date: 2018-08
Language: eng
Number of pages: 10
Belongs to series: Atherosclerosis
ISSN: 0021-9150
URI: http://hdl.handle.net/10138/300430
Abstract: Background and aims: Subendothelial interaction of LDL with extracellular matrix drives atherogenesis. This interaction can be strengthened by proteolytic modification of LDL. Mast cells (MCs) are present in atherosclerotic lesions, and upon activation, they degranulate and release a variety of neutral proteases. Here we studied the ability of MC proteases to cleave apoB-100 of LDL and affect the binding of LDL to proteoglycans. Methods: Mature human MCs were differentiated from human peripheral blood-derived CD34(+) progenitors in vitro and activated with calcium ionophore to generate MC-conditioned medium. LDL was incubated in the MC-conditioned medium or with individual MC proteases, and the binding of native and modified LDL to isolated human aortic proteoglycans or to human atherosclerotic plaques ex vivo was determined. MC proteases in atherosclerotic human coronary artery lesions were detected by immunofluorescence and qPCR. Results: Activated human MCs released the neutral proteases tryptase, chymase, carboxypeptidase A3, cathepsin G, and granzyme B. Of these, cathepsin G degraded most efficiently apoB-100, induced LDL fusion, and enhanced binding of LDL to isolated human aortic proteoglycans and human atherosclerotic lesions ex vivo. Double immunofluoresence staining of human atherosclerotic coronary arteries for tryptase and cathepsin G indicated that lesional MCs contain cathepsin G. In the lesions, expression of cathepsin G correlated with the expression of tryptase and chymase, but not with that of neutrophil proteinase 3. Conclusions: The present study suggests that cathepsin G in human atherosclerotic lesions is largely derived from MCs and that activated MCs may contribute to atherogenesis by enhancing LDL retention. (C) 2018 Elsevier B.V. All rights reserved.
Subject: (3–7) apoB
Lipoprotein
LDL
Mast cell
Cathepsin G
Tryptase
Proteoglycan
(3-7) apoB
HUMAN CAROTID ARTERIES
INCREASED EXPRESSION
HUMAN MACROPHAGES
LOW-DENSITY-LIPOPROTEIN
NEUTROPHIL ELASTASE
APOLIPOPROTEIN-B
IN-VITRO
HUMAN ATHEROSCLEROTIC LESIONS
HUMAN AORTIC PROTEOGLYCANS
CATHEPSIN-G
3111 Biomedicine
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