Calorie Restriction Curbs Proinflammation That Accompanies Arterial Aging, Preserving a Youthful Phenotype

Background Aging exponentially increases the incidence of morbidity and mortality of quintessential cardiovascular disease mainly due to arterial proinflammatory shifts at the molecular, cellular, and tissue levels within the arterial wall. Calorie restriction (CR) in rats improves arterial function...

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Main Authors: Mingyi Wang, Li Zhang, Wanqu Zhu, Jing Zhang, Soo Hyuk Kim, Yushi Wang, Leng Ni, Richard Telljohann, Robert E. Monticone, Kimberly McGraw, Lijuan Liu, Rafael de Cabo, Edward G. Lakatta
Format: Article
Language:English
Published: Wiley 2018-09-01
Series:Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
Subjects:
Online Access:https://www.ahajournals.org/doi/10.1161/JAHA.118.009112
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author Mingyi Wang
Li Zhang
Wanqu Zhu
Jing Zhang
Soo Hyuk Kim
Yushi Wang
Leng Ni
Richard Telljohann
Robert E. Monticone
Kimberly McGraw
Lijuan Liu
Rafael de Cabo
Edward G. Lakatta
author_facet Mingyi Wang
Li Zhang
Wanqu Zhu
Jing Zhang
Soo Hyuk Kim
Yushi Wang
Leng Ni
Richard Telljohann
Robert E. Monticone
Kimberly McGraw
Lijuan Liu
Rafael de Cabo
Edward G. Lakatta
author_sort Mingyi Wang
collection DOAJ
description Background Aging exponentially increases the incidence of morbidity and mortality of quintessential cardiovascular disease mainly due to arterial proinflammatory shifts at the molecular, cellular, and tissue levels within the arterial wall. Calorie restriction (CR) in rats improves arterial function and extends both health span and life span. How CR affects the proinflammatory landscape of molecular, cellular, and tissue phenotypic shifts within the arterial wall in rats, however, remains to be elucidated. Methods and Results Aortae were harvested from young (6‐month‐old) and old (24‐month‐old) Fischer 344 rats, fed ad libitum and a second group maintained on a 40% CR beginning at 1 month of age. Histopathologic and morphometric analysis of the arterial wall demonstrated that CR markedly reduced age‐associated intimal medial thickening, collagen deposition, and elastin fractionation/degradation within the arterial walls. Immunostaining/blotting showed that CR effectively prevented an age‐associated increase in the density of platelet‐derived growth factor, matrix metalloproteinase type II activity, and transforming growth factor beta 1 and its downstream signaling molecules, phospho‐mothers against decapentaplegic homolog‐2/3 (p‐SMAD‐2/3) in the arterial wall. In early passage cultured vascular smooth muscle cells isolated from AL and CR rat aortae, CR alleviated the age‐associated vascular smooth muscle cell phenotypic shifts, profibrogenic signaling, and migration/proliferation in response to platelet‐derived growth factor. Conclusions CR reduces matrix and cellular proinflammation associated with aging that occurs within the aortic wall and that are attributable to platelet‐derived growth factor signaling. Thus, CR reduces the platelet‐derived growth factor–associated signaling cascade, contributing to the postponement of biological aging and preservation of a more youthful aortic wall phenotype.
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spelling doaj.art-1cb3608c3ec6469ea847c976e5e863a82022-12-22T02:38:32ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802018-09-0171810.1161/JAHA.118.009112Calorie Restriction Curbs Proinflammation That Accompanies Arterial Aging, Preserving a Youthful PhenotypeMingyi Wang0Li Zhang1Wanqu Zhu2Jing Zhang3Soo Hyuk Kim4Yushi Wang5Leng Ni6Richard Telljohann7Robert E. Monticone8Kimberly McGraw9Lijuan Liu10Rafael de Cabo11Edward G. Lakatta12Laboratory of Cardiovascular Science National Institute on Aging National Institutes of Health Biomedical Research Center (BRC) Baltimore MDLaboratory of Cardiovascular Science National Institute on Aging National Institutes of Health Biomedical Research Center (BRC) Baltimore MDLaboratory of Cardiovascular Science National Institute on Aging National Institutes of Health Biomedical Research Center (BRC) Baltimore MDLaboratory of Cardiovascular Science National Institute on Aging National Institutes of Health Biomedical Research Center (BRC) Baltimore MDLaboratory of Cardiovascular Science National Institute on Aging National Institutes of Health Biomedical Research Center (BRC) Baltimore MDLaboratory of Cardiovascular Science National Institute on Aging National Institutes of Health Biomedical Research Center (BRC) Baltimore MDLaboratory of Cardiovascular Science National Institute on Aging National Institutes of Health Biomedical Research Center (BRC) Baltimore MDLaboratory of Cardiovascular Science National Institute on Aging National Institutes of Health Biomedical Research Center (BRC) Baltimore MDLaboratory of Cardiovascular Science National Institute on Aging National Institutes of Health Biomedical Research Center (BRC) Baltimore MDLaboratory of Cardiovascular Science National Institute on Aging National Institutes of Health Biomedical Research Center (BRC) Baltimore MDLaboratory of Cardiovascular Science National Institute on Aging National Institutes of Health Biomedical Research Center (BRC) Baltimore MDExperimental Gerontology Section, Translational Gerontology Branch National Institute on Aging National Institutes of Health Biomedical Research Center (BRC) Baltimore MDLaboratory of Cardiovascular Science National Institute on Aging National Institutes of Health Biomedical Research Center (BRC) Baltimore MDBackground Aging exponentially increases the incidence of morbidity and mortality of quintessential cardiovascular disease mainly due to arterial proinflammatory shifts at the molecular, cellular, and tissue levels within the arterial wall. Calorie restriction (CR) in rats improves arterial function and extends both health span and life span. How CR affects the proinflammatory landscape of molecular, cellular, and tissue phenotypic shifts within the arterial wall in rats, however, remains to be elucidated. Methods and Results Aortae were harvested from young (6‐month‐old) and old (24‐month‐old) Fischer 344 rats, fed ad libitum and a second group maintained on a 40% CR beginning at 1 month of age. Histopathologic and morphometric analysis of the arterial wall demonstrated that CR markedly reduced age‐associated intimal medial thickening, collagen deposition, and elastin fractionation/degradation within the arterial walls. Immunostaining/blotting showed that CR effectively prevented an age‐associated increase in the density of platelet‐derived growth factor, matrix metalloproteinase type II activity, and transforming growth factor beta 1 and its downstream signaling molecules, phospho‐mothers against decapentaplegic homolog‐2/3 (p‐SMAD‐2/3) in the arterial wall. In early passage cultured vascular smooth muscle cells isolated from AL and CR rat aortae, CR alleviated the age‐associated vascular smooth muscle cell phenotypic shifts, profibrogenic signaling, and migration/proliferation in response to platelet‐derived growth factor. Conclusions CR reduces matrix and cellular proinflammation associated with aging that occurs within the aortic wall and that are attributable to platelet‐derived growth factor signaling. Thus, CR reduces the platelet‐derived growth factor–associated signaling cascade, contributing to the postponement of biological aging and preservation of a more youthful aortic wall phenotype.https://www.ahajournals.org/doi/10.1161/JAHA.118.009112agingarterial remodelingcalorie restrictionproinflammationratsvascular smooth muscle cells
spellingShingle Mingyi Wang
Li Zhang
Wanqu Zhu
Jing Zhang
Soo Hyuk Kim
Yushi Wang
Leng Ni
Richard Telljohann
Robert E. Monticone
Kimberly McGraw
Lijuan Liu
Rafael de Cabo
Edward G. Lakatta
Calorie Restriction Curbs Proinflammation That Accompanies Arterial Aging, Preserving a Youthful Phenotype
Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
aging
arterial remodeling
calorie restriction
proinflammation
rats
vascular smooth muscle cells
title Calorie Restriction Curbs Proinflammation That Accompanies Arterial Aging, Preserving a Youthful Phenotype
title_full Calorie Restriction Curbs Proinflammation That Accompanies Arterial Aging, Preserving a Youthful Phenotype
title_fullStr Calorie Restriction Curbs Proinflammation That Accompanies Arterial Aging, Preserving a Youthful Phenotype
title_full_unstemmed Calorie Restriction Curbs Proinflammation That Accompanies Arterial Aging, Preserving a Youthful Phenotype
title_short Calorie Restriction Curbs Proinflammation That Accompanies Arterial Aging, Preserving a Youthful Phenotype
title_sort calorie restriction curbs proinflammation that accompanies arterial aging preserving a youthful phenotype
topic aging
arterial remodeling
calorie restriction
proinflammation
rats
vascular smooth muscle cells
url https://www.ahajournals.org/doi/10.1161/JAHA.118.009112
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