Modification of cardiac progenitor cell-derived exosomes by miR-322 provides protection against myocardial infarction through nox2-dependent angiogenesis

Seock Won Youn, Yang Li, Young Mee Kim, Sudhahar Varadarajan, Kareem Abdelsaid, Ha Won Kim, Yutao Liu, David J Fulton, Muhammad Ashraf, Yao Liang Tang, Tohru Fukai, Masuko Fukai

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Myocardial infarction (MI) is the primary cause of cardiovascular mortality, and therapeutic strategies to prevent or mitigate the consequences of MI are a high priority. Cardiac progenitor cells (CPCs) have been used to treat cardiac injury post-MI, and despite poor engraftment, they have been shown to inhibit apoptosis and to promote angiogenesis through poorly understood paracrine effects. We previously reported that the direct injection of exosomes derived from CPCs (CPCexo) into mouse hearts provides protection against apoptosis in a model of acute ischemia/reperfusion injury. Moreover, we and others have reported that reactive oxygen species (ROS) derived from NADPH oxidase (NOX) can enhance angiogenesis in endothelial cells (ECs). Here we examined whether bioengineered CPCexo transfected with a pro-angiogenic miR-322 (CPCexo-322) can improve therapeutic efficacy in a mouse model of MI as compared to CPCexo. Systemic administration of CPCexo-322 in mice after ischemic injury provided greater protection post-MI than control CPCexo, in part, through enhanced angiogenesis in the border zones of infarcted hearts. Mechanistically, the treatment of cultured human ECs with CPCexo-322 resulted in a greater angiogenic response, as determined by increased EC migration and capillary tube formation via increased Nox2-derived ROS. Our study reveals that the engineering of CPCexo via microRNA (miR) programing can enhance angiogenesis, and this may be an effective therapeutic strategy for the treatment of ischemic cardiovascular diseases.

Original languageEnglish (US)
Article number18
JournalAntioxidants
Volume8
Issue number1
DOIs
StatePublished - Jan 1 2019

Fingerprint

Exosomes
Endothelial cells
MicroRNAs
Stem Cells
Myocardial Infarction
Reactive Oxygen Species
Endothelial Cells
Apoptosis
Capillary tubes
NADPH Oxidase
Direct injection
Therapeutics
Wounds and Injuries
Reperfusion Injury
Cell Movement
Cardiovascular Diseases
Injections
Mortality

Keywords

  • Angiogenesis
  • Cardiac progenitor cell
  • Exosome
  • MiR-322
  • Myocardial infarction
  • NADPH oxidase
  • Reactive oxygen species

ASJC Scopus subject areas

  • Physiology
  • Biochemistry
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

Cite this

@article{7f9c661e7a814fbf8efa1d5f87898aeb,
title = "Modification of cardiac progenitor cell-derived exosomes by miR-322 provides protection against myocardial infarction through nox2-dependent angiogenesis",
abstract = "Myocardial infarction (MI) is the primary cause of cardiovascular mortality, and therapeutic strategies to prevent or mitigate the consequences of MI are a high priority. Cardiac progenitor cells (CPCs) have been used to treat cardiac injury post-MI, and despite poor engraftment, they have been shown to inhibit apoptosis and to promote angiogenesis through poorly understood paracrine effects. We previously reported that the direct injection of exosomes derived from CPCs (CPCexo) into mouse hearts provides protection against apoptosis in a model of acute ischemia/reperfusion injury. Moreover, we and others have reported that reactive oxygen species (ROS) derived from NADPH oxidase (NOX) can enhance angiogenesis in endothelial cells (ECs). Here we examined whether bioengineered CPCexo transfected with a pro-angiogenic miR-322 (CPCexo-322) can improve therapeutic efficacy in a mouse model of MI as compared to CPCexo. Systemic administration of CPCexo-322 in mice after ischemic injury provided greater protection post-MI than control CPCexo, in part, through enhanced angiogenesis in the border zones of infarcted hearts. Mechanistically, the treatment of cultured human ECs with CPCexo-322 resulted in a greater angiogenic response, as determined by increased EC migration and capillary tube formation via increased Nox2-derived ROS. Our study reveals that the engineering of CPCexo via microRNA (miR) programing can enhance angiogenesis, and this may be an effective therapeutic strategy for the treatment of ischemic cardiovascular diseases.",
keywords = "Angiogenesis, Cardiac progenitor cell, Exosome, MiR-322, Myocardial infarction, NADPH oxidase, Reactive oxygen species",
author = "Youn, {Seock Won} and Yang Li and Kim, {Young Mee} and Sudhahar Varadarajan and Kareem Abdelsaid and Kim, {Ha Won} and Yutao Liu and Fulton, {David J} and Muhammad Ashraf and Tang, {Yao Liang} and Tohru Fukai and Masuko Fukai",
year = "2019",
month = "1",
day = "1",
doi = "10.3390/antiox8010018",
language = "English (US)",
volume = "8",
journal = "Antioxidants",
issn = "2076-3921",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "1",

}

TY - JOUR

T1 - Modification of cardiac progenitor cell-derived exosomes by miR-322 provides protection against myocardial infarction through nox2-dependent angiogenesis

AU - Youn, Seock Won

AU - Li, Yang

AU - Kim, Young Mee

AU - Varadarajan, Sudhahar

AU - Abdelsaid, Kareem

AU - Kim, Ha Won

AU - Liu, Yutao

AU - Fulton, David J

AU - Ashraf, Muhammad

AU - Tang, Yao Liang

AU - Fukai, Tohru

AU - Fukai, Masuko

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Myocardial infarction (MI) is the primary cause of cardiovascular mortality, and therapeutic strategies to prevent or mitigate the consequences of MI are a high priority. Cardiac progenitor cells (CPCs) have been used to treat cardiac injury post-MI, and despite poor engraftment, they have been shown to inhibit apoptosis and to promote angiogenesis through poorly understood paracrine effects. We previously reported that the direct injection of exosomes derived from CPCs (CPCexo) into mouse hearts provides protection against apoptosis in a model of acute ischemia/reperfusion injury. Moreover, we and others have reported that reactive oxygen species (ROS) derived from NADPH oxidase (NOX) can enhance angiogenesis in endothelial cells (ECs). Here we examined whether bioengineered CPCexo transfected with a pro-angiogenic miR-322 (CPCexo-322) can improve therapeutic efficacy in a mouse model of MI as compared to CPCexo. Systemic administration of CPCexo-322 in mice after ischemic injury provided greater protection post-MI than control CPCexo, in part, through enhanced angiogenesis in the border zones of infarcted hearts. Mechanistically, the treatment of cultured human ECs with CPCexo-322 resulted in a greater angiogenic response, as determined by increased EC migration and capillary tube formation via increased Nox2-derived ROS. Our study reveals that the engineering of CPCexo via microRNA (miR) programing can enhance angiogenesis, and this may be an effective therapeutic strategy for the treatment of ischemic cardiovascular diseases.

AB - Myocardial infarction (MI) is the primary cause of cardiovascular mortality, and therapeutic strategies to prevent or mitigate the consequences of MI are a high priority. Cardiac progenitor cells (CPCs) have been used to treat cardiac injury post-MI, and despite poor engraftment, they have been shown to inhibit apoptosis and to promote angiogenesis through poorly understood paracrine effects. We previously reported that the direct injection of exosomes derived from CPCs (CPCexo) into mouse hearts provides protection against apoptosis in a model of acute ischemia/reperfusion injury. Moreover, we and others have reported that reactive oxygen species (ROS) derived from NADPH oxidase (NOX) can enhance angiogenesis in endothelial cells (ECs). Here we examined whether bioengineered CPCexo transfected with a pro-angiogenic miR-322 (CPCexo-322) can improve therapeutic efficacy in a mouse model of MI as compared to CPCexo. Systemic administration of CPCexo-322 in mice after ischemic injury provided greater protection post-MI than control CPCexo, in part, through enhanced angiogenesis in the border zones of infarcted hearts. Mechanistically, the treatment of cultured human ECs with CPCexo-322 resulted in a greater angiogenic response, as determined by increased EC migration and capillary tube formation via increased Nox2-derived ROS. Our study reveals that the engineering of CPCexo via microRNA (miR) programing can enhance angiogenesis, and this may be an effective therapeutic strategy for the treatment of ischemic cardiovascular diseases.

KW - Angiogenesis

KW - Cardiac progenitor cell

KW - Exosome

KW - MiR-322

KW - Myocardial infarction

KW - NADPH oxidase

KW - Reactive oxygen species

UR - http://www.scopus.com/inward/record.url?scp=85060114633&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85060114633&partnerID=8YFLogxK

U2 - 10.3390/antiox8010018

DO - 10.3390/antiox8010018

M3 - Article

VL - 8

JO - Antioxidants

JF - Antioxidants

SN - 2076-3921

IS - 1

M1 - 18

ER -