TY - JOUR
T1 - PAPP-A and the IGF system in atherosclerosis
T2 - What’s up, what’s down?
AU - Steffensen, Lasse B.
AU - Conover, Cheryl A.
AU - Oxvig, Claus
N1 - Funding Information:
This work was supported by the Centre for Individualized Medicine in Arterial Diseases, Odense University Hospital (to L. B. Steffensen); National Heart, Lung, and Blood Institute Grant R01-HL-074871 (to C. A. Conover); and Independent Research Fund Denmark (to C. Oxvig).
Publisher Copyright:
Copyright © 2019 the American Physiological Society.
PY - 2019/11
Y1 - 2019/11
N2 - Steffensen LB, Conover CA, Oxvig C. PAPP-A and the IGF system in atherosclerosis: what’s up, what’s down? Am J Physiol Heart Circ Physiol 317: H1039 –H1049, 2019. First published September 13, 2019; doi:10.1152/ajpheart.00395.2019.—Pregnancy-associated plasma protein-A (PAPP-A) is a metalloproteinase with a well-established role in releasing bioactive insulin-like growth factor-1 (IGF-1) from IGF-binding protein-2, -4, and -5 by proteolytic processing of these. The IGF system has repeatedly been suggested to be involved in the pathology of atherosclerosis, and both PAPP-A and IGF-1 are proposed biomarkers and therapeutic targets for this disease. Several experimental approaches based on atherosclerosis mouse models have been undertaken to obtain causative and mechanistic insight to the role of these molecules in atherogenesis. However, reports seem conflicting. The literature suggests that PAPP-A is detrimental, while IGF-1 is beneficial. This raises important questions that need to be addressed. Here we summarize the various studies and discuss potential underlying explanations for this seemingly inconsistency with the objective of better understanding complexities and limitations when manipulating the IGF system in mouse models of atherosclerosis. A debate clarifying what’s up and what’s down is highly warranted going forward with the ultimate goal of improving atherosclerosis therapy by targeting the IGF system.
AB - Steffensen LB, Conover CA, Oxvig C. PAPP-A and the IGF system in atherosclerosis: what’s up, what’s down? Am J Physiol Heart Circ Physiol 317: H1039 –H1049, 2019. First published September 13, 2019; doi:10.1152/ajpheart.00395.2019.—Pregnancy-associated plasma protein-A (PAPP-A) is a metalloproteinase with a well-established role in releasing bioactive insulin-like growth factor-1 (IGF-1) from IGF-binding protein-2, -4, and -5 by proteolytic processing of these. The IGF system has repeatedly been suggested to be involved in the pathology of atherosclerosis, and both PAPP-A and IGF-1 are proposed biomarkers and therapeutic targets for this disease. Several experimental approaches based on atherosclerosis mouse models have been undertaken to obtain causative and mechanistic insight to the role of these molecules in atherogenesis. However, reports seem conflicting. The literature suggests that PAPP-A is detrimental, while IGF-1 is beneficial. This raises important questions that need to be addressed. Here we summarize the various studies and discuss potential underlying explanations for this seemingly inconsistency with the objective of better understanding complexities and limitations when manipulating the IGF system in mouse models of atherosclerosis. A debate clarifying what’s up and what’s down is highly warranted going forward with the ultimate goal of improving atherosclerosis therapy by targeting the IGF system.
KW - Atherosclerosis
KW - IGF system
KW - Mouse models
KW - PAPP-A
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U2 - 10.1152/ajpheart.00395.2019
DO - 10.1152/ajpheart.00395.2019
M3 - Review article
C2 - 31518159
AN - SCOPUS:85074118307
VL - 317
SP - H1039-H1049
JO - American Journal of Physiology
JF - American Journal of Physiology
SN - 0363-6135
IS - 5
ER -