TY - JOUR
T1 - Extracellular matrix roles in cardiorenal fibrosis
T2 - Potential therapeutic targets for CVD and CKD in the elderly
AU - Toba, Hiroe
AU - Lindsey, Merry L.
N1 - Funding Information:
This work was supported by the National Institutes of Health (NIH) HL075360, HL129823, and GM114833 to MLL, and by HL051971, GM104357, and GM115428; and the Biomedical Laboratory Research and Development Service of the Veterans Affairs Office of Research and Development Award 5I01BX000505 to MLL; and grant-in-aids for scientific research from Kyoto Pharmaceutical University 16-05 and Hoansha Foundation to HT. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Institutes of Health or the U.S. Department of Veterans Affairs.
Funding Information:
This work was supported by the National Institutes of Health (NIH) HL075360 , HL129823 , and GM114833 to MLL, and by HL051971 , GM104357 , and GM115428 ; and the Biomedical Laboratory Research and Development Service of the Veterans Affairs Office of Research and Development Award 5I01BX000505 to MLL; and grant-in-aids for scientific research from Kyoto Pharmaceutical University 16-05 and Hoansha Foundation to HT. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Institutes of Health or the U.S. Department of Veterans Affairs .
Publisher Copyright:
© 2018 Elsevier Inc.
PY - 2019/1
Y1 - 2019/1
N2 - Whereas hypertension, diabetes, and dyslipidemia are age-related risk factors for cardiovascular disease (CVD) and chronic kidney disease (CKD), aging alone is an independent risk factor. With advancing age, the heart and kidney gradually but significantly undergo inflammation and subsequent fibrosis, which eventually results in an irreversible decline in organ physiology. Through cardiorenal network interactions, cardiac dysfunction leads to and responds to renal injury, and both facilitate aging effects. Thus, a comprehensive strategy is needed to evaluate the cardiorenal aging network. Common hallmarks shared across systems include extracellular matrix (ECM) accumulation, along with upregulation of matrix metalloproteinases (MMPs) including MMP-9. The wide range of MMP-9 substrates, including ECM components and inflammatory cytokines, implicates MMP-9 in a variety of pathological and age-related processes. In particular, there is strong evidence that inflammatory cell-derived MMP-9 exacerbates cardiorenal aging. This review explores the potential therapeutic targets against CVD and CKD in the elderly, focusing on ECM and MMP roles.
AB - Whereas hypertension, diabetes, and dyslipidemia are age-related risk factors for cardiovascular disease (CVD) and chronic kidney disease (CKD), aging alone is an independent risk factor. With advancing age, the heart and kidney gradually but significantly undergo inflammation and subsequent fibrosis, which eventually results in an irreversible decline in organ physiology. Through cardiorenal network interactions, cardiac dysfunction leads to and responds to renal injury, and both facilitate aging effects. Thus, a comprehensive strategy is needed to evaluate the cardiorenal aging network. Common hallmarks shared across systems include extracellular matrix (ECM) accumulation, along with upregulation of matrix metalloproteinases (MMPs) including MMP-9. The wide range of MMP-9 substrates, including ECM components and inflammatory cytokines, implicates MMP-9 in a variety of pathological and age-related processes. In particular, there is strong evidence that inflammatory cell-derived MMP-9 exacerbates cardiorenal aging. This review explores the potential therapeutic targets against CVD and CKD in the elderly, focusing on ECM and MMP roles.
KW - Cardiorenal aging
KW - Extracellular matrix
KW - Fibrosis
KW - Inflammaging
KW - Matrix metalloproteinase-9
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U2 - 10.1016/j.pharmthera.2018.08.014
DO - 10.1016/j.pharmthera.2018.08.014
M3 - Review article
C2 - 30149103
AN - SCOPUS:85052938808
VL - 193
SP - 99
EP - 120
JO - Pharmacology and Therapeutics
JF - Pharmacology and Therapeutics
SN - 0163-7258
ER -