Low Density Lipoprotein Receptor-Related Protein-1 in Cardiac Inflammation and Infarct Healing

Acute myocardial infarction (AMI) leads to myocardial cell death and ensuing sterile inflammatory response, which represents an attempt to clear cellular debris and promote cardiac repair. However, an overwhelming, unopposed or unresolved inflammatory response following AMI leads to further injury,...

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Main Authors: Nicola Potere, Marco Giuseppe Del Buono, Adolfo Gabriele Mauro, Antonio Abbate, Stefano Toldo
Format: Article
Language:English
Published: Frontiers Media S.A. 2019-04-01
Series:Frontiers in Cardiovascular Medicine
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fcvm.2019.00051/full
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spelling doaj-6080f0d305eb41f4a32210e03c11832b2020-11-25T00:14:00ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2019-04-01610.3389/fcvm.2019.00051456776Low Density Lipoprotein Receptor-Related Protein-1 in Cardiac Inflammation and Infarct HealingNicola Potere0Marco Giuseppe Del Buono1Marco Giuseppe Del Buono2Adolfo Gabriele Mauro3Antonio Abbate4Stefano Toldo5VCU Pauley Heart Center, Virginia Commonwealth University, Richmond, VA, United StatesVCU Pauley Heart Center, Virginia Commonwealth University, Richmond, VA, United StatesDepartment of Cardiovascular and Thoracic Sciences, Catholic University of the Sacred Heart, Rome, ItalyVCU Pauley Heart Center, Virginia Commonwealth University, Richmond, VA, United StatesVCU Pauley Heart Center, Virginia Commonwealth University, Richmond, VA, United StatesVCU Pauley Heart Center, Virginia Commonwealth University, Richmond, VA, United StatesAcute myocardial infarction (AMI) leads to myocardial cell death and ensuing sterile inflammatory response, which represents an attempt to clear cellular debris and promote cardiac repair. However, an overwhelming, unopposed or unresolved inflammatory response following AMI leads to further injury, worse remodeling and heart failure (HF). Additional therapies are therefore warranted to blunt the inflammatory response associated with ischemia and reperfusion and prevent long-term adverse events. Low-density lipoprotein receptor-related protein 1 (LRP1) is a ubiquitous endocytic cell surface receptor with the ability to recognize a wide range of structurally and functionally diverse ligands. LRP1 transduces multiple intracellular signal pathways regulating the inflammatory reaction, tissue remodeling and cell survival after organ injury. In preclinical studies, activation of LRP1-mediated signaling in the heart with non-selective and selective LRP1 agonists is linked with a powerful cardioprotective effect, reducing infarct size and cardiac dysfunction after AMI. The data from early phase clinical studies with plasma-derived α1-antitrypsin (AAT), an endogenous LRP1 agonist, and SP16 peptide, a synthetic LRP1 agonist, support the translational value of LRP1 as a novel therapeutic target in AMI. In this review, we will summarize the cellular and molecular bases of LRP1 functions in modulating the inflammatory reaction and the reparative process after injury in various peripheral tissues, and discuss recent evidences implicating LRP1 in myocardial inflammation and infarct healing.https://www.frontiersin.org/article/10.3389/fcvm.2019.00051/fulllow-density lipoprotein receptor-related protein-1LRP1acute myocardial infarctionischemia-reperfusioninflammationcardioprotection
collection DOAJ
language English
format Article
sources DOAJ
author Nicola Potere
Marco Giuseppe Del Buono
Marco Giuseppe Del Buono
Adolfo Gabriele Mauro
Antonio Abbate
Stefano Toldo
spellingShingle Nicola Potere
Marco Giuseppe Del Buono
Marco Giuseppe Del Buono
Adolfo Gabriele Mauro
Antonio Abbate
Stefano Toldo
Low Density Lipoprotein Receptor-Related Protein-1 in Cardiac Inflammation and Infarct Healing
Frontiers in Cardiovascular Medicine
low-density lipoprotein receptor-related protein-1
LRP1
acute myocardial infarction
ischemia-reperfusion
inflammation
cardioprotection
author_facet Nicola Potere
Marco Giuseppe Del Buono
Marco Giuseppe Del Buono
Adolfo Gabriele Mauro
Antonio Abbate
Stefano Toldo
author_sort Nicola Potere
title Low Density Lipoprotein Receptor-Related Protein-1 in Cardiac Inflammation and Infarct Healing
title_short Low Density Lipoprotein Receptor-Related Protein-1 in Cardiac Inflammation and Infarct Healing
title_full Low Density Lipoprotein Receptor-Related Protein-1 in Cardiac Inflammation and Infarct Healing
title_fullStr Low Density Lipoprotein Receptor-Related Protein-1 in Cardiac Inflammation and Infarct Healing
title_full_unstemmed Low Density Lipoprotein Receptor-Related Protein-1 in Cardiac Inflammation and Infarct Healing
title_sort low density lipoprotein receptor-related protein-1 in cardiac inflammation and infarct healing
publisher Frontiers Media S.A.
series Frontiers in Cardiovascular Medicine
issn 2297-055X
publishDate 2019-04-01
description Acute myocardial infarction (AMI) leads to myocardial cell death and ensuing sterile inflammatory response, which represents an attempt to clear cellular debris and promote cardiac repair. However, an overwhelming, unopposed or unresolved inflammatory response following AMI leads to further injury, worse remodeling and heart failure (HF). Additional therapies are therefore warranted to blunt the inflammatory response associated with ischemia and reperfusion and prevent long-term adverse events. Low-density lipoprotein receptor-related protein 1 (LRP1) is a ubiquitous endocytic cell surface receptor with the ability to recognize a wide range of structurally and functionally diverse ligands. LRP1 transduces multiple intracellular signal pathways regulating the inflammatory reaction, tissue remodeling and cell survival after organ injury. In preclinical studies, activation of LRP1-mediated signaling in the heart with non-selective and selective LRP1 agonists is linked with a powerful cardioprotective effect, reducing infarct size and cardiac dysfunction after AMI. The data from early phase clinical studies with plasma-derived α1-antitrypsin (AAT), an endogenous LRP1 agonist, and SP16 peptide, a synthetic LRP1 agonist, support the translational value of LRP1 as a novel therapeutic target in AMI. In this review, we will summarize the cellular and molecular bases of LRP1 functions in modulating the inflammatory reaction and the reparative process after injury in various peripheral tissues, and discuss recent evidences implicating LRP1 in myocardial inflammation and infarct healing.
topic low-density lipoprotein receptor-related protein-1
LRP1
acute myocardial infarction
ischemia-reperfusion
inflammation
cardioprotection
url https://www.frontiersin.org/article/10.3389/fcvm.2019.00051/full
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