Age and SPARC Change the Extracellular Matrix Composition of the Left Ventricle

Secreted protein acidic and rich in cysteine (SPARC), a collagen-binding matricellular protein, has been implicated in procollagen processing and deposition. The aim of this study was to investigate age- and SPARC-dependent changes in protein composition of the cardiac extracellular matrix (ECM). We...

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Main Authors:	de Castro Brás, Lisandra E., Toba, Hiroe, Baicu, Catalin F., Zile, Michael R., Weintraub, Susan T., Lindsey, Merry L., Bradshaw, Amy D.
Format:	Online
Language:	English
Published:	Hindawi Publishing Corporation 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3982264/

id	pubmed-3982264
recordtype	oai_dc
spelling	pubmed-39822642014-04-29 Age and SPARC Change the Extracellular Matrix Composition of the Left Ventricle de Castro Brás, Lisandra E. Toba, Hiroe Baicu, Catalin F. Zile, Michael R. Weintraub, Susan T. Lindsey, Merry L. Bradshaw, Amy D. Research Article Secreted protein acidic and rich in cysteine (SPARC), a collagen-binding matricellular protein, has been implicated in procollagen processing and deposition. The aim of this study was to investigate age- and SPARC-dependent changes in protein composition of the cardiac extracellular matrix (ECM). We studied 6 groups of mice (n = 4/group): young (4-5 months old), middle-aged (11-12 m.o.), and old (18–29 m.o.) C57BL/6J wild type (WT) and SPARC null. The left ventricle (LV) was decellularized to enrich for ECM proteins. Protein extracts were separated by SDS-PAGE, digested in-gel, and analyzed by HPLC-ESI-MS/MS. Relative quantification was performed by spectral counting, and changes in specific proteins were validated by immunoblotting. We identified 321 proteins, of which 44 proteins were extracellular proteins. Of these proteins, collagen III levels were lower in the old null mice compared to WT, suggestive of a role for SPARC in collagen deposition. Additionally, fibrillin showed a significant increase in the null middle-aged group, suggestive of increased microfibril deposition in the absence of SPARC. Collagen VI increased with age in both genotypes (>3-fold), while collagen IV showed increased age-associated levels only in the WT animals (4-fold, P < 0.05). These changes may explain the previously reported age-associated increases in LV stiffness. In summary, our data suggest SPARC is a possible therapeutic target for aging induced LV dysfunction. Hindawi Publishing Corporation 2014 2014-03-24 /pmc/articles/PMC3982264/ /pubmed/24783223 http://dx.doi.org/10.1155/2014/810562 Text en Copyright © 2014 Lisandra E. de Castro Brás et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	de Castro Brás, Lisandra E. Toba, Hiroe Baicu, Catalin F. Zile, Michael R. Weintraub, Susan T. Lindsey, Merry L. Bradshaw, Amy D.
spellingShingle	de Castro Brás, Lisandra E. Toba, Hiroe Baicu, Catalin F. Zile, Michael R. Weintraub, Susan T. Lindsey, Merry L. Bradshaw, Amy D. Age and SPARC Change the Extracellular Matrix Composition of the Left Ventricle
author_facet	de Castro Brás, Lisandra E. Toba, Hiroe Baicu, Catalin F. Zile, Michael R. Weintraub, Susan T. Lindsey, Merry L. Bradshaw, Amy D.
author_sort	de Castro Brás, Lisandra E.
title	Age and SPARC Change the Extracellular Matrix Composition of the Left Ventricle
title_short	Age and SPARC Change the Extracellular Matrix Composition of the Left Ventricle
title_full	Age and SPARC Change the Extracellular Matrix Composition of the Left Ventricle
title_fullStr	Age and SPARC Change the Extracellular Matrix Composition of the Left Ventricle
title_full_unstemmed	Age and SPARC Change the Extracellular Matrix Composition of the Left Ventricle
title_sort	age and sparc change the extracellular matrix composition of the left ventricle
description	Secreted protein acidic and rich in cysteine (SPARC), a collagen-binding matricellular protein, has been implicated in procollagen processing and deposition. The aim of this study was to investigate age- and SPARC-dependent changes in protein composition of the cardiac extracellular matrix (ECM). We studied 6 groups of mice (n = 4/group): young (4-5 months old), middle-aged (11-12 m.o.), and old (18–29 m.o.) C57BL/6J wild type (WT) and SPARC null. The left ventricle (LV) was decellularized to enrich for ECM proteins. Protein extracts were separated by SDS-PAGE, digested in-gel, and analyzed by HPLC-ESI-MS/MS. Relative quantification was performed by spectral counting, and changes in specific proteins were validated by immunoblotting. We identified 321 proteins, of which 44 proteins were extracellular proteins. Of these proteins, collagen III levels were lower in the old null mice compared to WT, suggestive of a role for SPARC in collagen deposition. Additionally, fibrillin showed a significant increase in the null middle-aged group, suggestive of increased microfibril deposition in the absence of SPARC. Collagen VI increased with age in both genotypes (>3-fold), while collagen IV showed increased age-associated levels only in the WT animals (4-fold, P < 0.05). These changes may explain the previously reported age-associated increases in LV stiffness. In summary, our data suggest SPARC is a possible therapeutic target for aging induced LV dysfunction.
publisher	Hindawi Publishing Corporation
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3982264/
_version_	1612076606406262784

Age and SPARC Change the Extracellular Matrix Composition of the Left Ventricle

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