Combining neuropeptide Y and mesenchymal stem cells reverses remodeling after myocardial infarction

Yigang Wang, Dongsheng Zhang, Muhammad Ashraf, Tiemin Zhao, Wei Huang, Atif Ashraf, Ambikaipakan Balasubramaniam

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Neuropeptide Y (NPY) induced reentry of differentiated rat neonatal and adult cardiomyocytes into the cell cycle. NPY also induced differentiation of bone marrow-derived mesenchymal stem cells (MSC) into cardiomyocytes following transplantation into infarcted myocardium. Rat neonatal and adult cardiomyocytes were treated in vitro with vehicle, NPY, fibroblast growth factor (FGF; 100 ng/ml), or FGF plus NPY. DNA synthesis, mitosis, and cytokinesis were determined by immunocytochemistry. NPY-induced MSC gene expression, cell migration, tube formation, and endothelial cell differentiation were analyzed. Male rat green fluorescent protein-MSC (2 × 106), pretreated with either vehicle or NPY (10-8 M) for 72 h, were injected into the border zone of the female myocardium following left anterior descending artery ligation. On day 30, heart function was assessed, and hearts were harvested for histological and immunohistochemical analyses. NPY increased 5-bromo-2′-deoxy-uridine incorporation and promoted both cytokinesis and mitosis in rat neonatal and adult myocytes. NPY also upregulated several genes required for mitosis in MSC, including aurora B kinase, FGF-2, cycline A2, eukaryotic initiation factor 4 E, and stromal cell-derived factor-1α. NPY directly induced neonatal and adult cardiomyocyte cell-cycle reentry and enhanced the number of differentiated cardiomyocytes from MSC in the infarcted myocardium, which corresponded to improved cardiac function, reduced fibrosis, ventricular remodeling, and increased angiomyogenesis. It is concluded that a combined treatment of NPY with MSC is a novel approach for cardiac repair.

Original languageEnglish (US)
Pages (from-to)H275-H286
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume298
Issue number1
DOIs
StatePublished - Jan 1 2010
Externally publishedYes

Fingerprint

Neuropeptide Y
Mesenchymal Stromal Cells
Myocardial Infarction
Cardiac Myocytes
Mitosis
Myocardium
Cytokinesis
Cell Cycle
Aurora Kinase B
Chemokine CXCL12
Ventricular Remodeling
Fibroblast Growth Factors
Fibroblast Growth Factor 2
Bromodeoxyuridine
Green Fluorescent Proteins
varespladib methyl
Muscle Cells
Cell Movement
Ligation
Cell Differentiation

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Combining neuropeptide Y and mesenchymal stem cells reverses remodeling after myocardial infarction. / Wang, Yigang; Zhang, Dongsheng; Ashraf, Muhammad; Zhao, Tiemin; Huang, Wei; Ashraf, Atif; Balasubramaniam, Ambikaipakan.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 298, No. 1, 01.01.2010, p. H275-H286.

Research output: Contribution to journalArticle

Wang, Yigang ; Zhang, Dongsheng ; Ashraf, Muhammad ; Zhao, Tiemin ; Huang, Wei ; Ashraf, Atif ; Balasubramaniam, Ambikaipakan. / Combining neuropeptide Y and mesenchymal stem cells reverses remodeling after myocardial infarction. In: American Journal of Physiology - Heart and Circulatory Physiology. 2010 ; Vol. 298, No. 1. pp. H275-H286.
@article{3a88341fddca4f60acf815088c8b2459,
title = "Combining neuropeptide Y and mesenchymal stem cells reverses remodeling after myocardial infarction",
abstract = "Neuropeptide Y (NPY) induced reentry of differentiated rat neonatal and adult cardiomyocytes into the cell cycle. NPY also induced differentiation of bone marrow-derived mesenchymal stem cells (MSC) into cardiomyocytes following transplantation into infarcted myocardium. Rat neonatal and adult cardiomyocytes were treated in vitro with vehicle, NPY, fibroblast growth factor (FGF; 100 ng/ml), or FGF plus NPY. DNA synthesis, mitosis, and cytokinesis were determined by immunocytochemistry. NPY-induced MSC gene expression, cell migration, tube formation, and endothelial cell differentiation were analyzed. Male rat green fluorescent protein-MSC (2 × 106), pretreated with either vehicle or NPY (10-8 M) for 72 h, were injected into the border zone of the female myocardium following left anterior descending artery ligation. On day 30, heart function was assessed, and hearts were harvested for histological and immunohistochemical analyses. NPY increased 5-bromo-2′-deoxy-uridine incorporation and promoted both cytokinesis and mitosis in rat neonatal and adult myocytes. NPY also upregulated several genes required for mitosis in MSC, including aurora B kinase, FGF-2, cycline A2, eukaryotic initiation factor 4 E, and stromal cell-derived factor-1α. NPY directly induced neonatal and adult cardiomyocyte cell-cycle reentry and enhanced the number of differentiated cardiomyocytes from MSC in the infarcted myocardium, which corresponded to improved cardiac function, reduced fibrosis, ventricular remodeling, and increased angiomyogenesis. It is concluded that a combined treatment of NPY with MSC is a novel approach for cardiac repair.",
author = "Yigang Wang and Dongsheng Zhang and Muhammad Ashraf and Tiemin Zhao and Wei Huang and Atif Ashraf and Ambikaipakan Balasubramaniam",
year = "2010",
month = "1",
day = "1",
doi = "10.1152/ajpheart.00765.2009",
language = "English (US)",
volume = "298",
pages = "H275--H286",
journal = "American Journal of Physiology - Heart and Circulatory Physiology",
issn = "0363-6135",
publisher = "American Physiological Society",
number = "1",

}

TY - JOUR

T1 - Combining neuropeptide Y and mesenchymal stem cells reverses remodeling after myocardial infarction

AU - Wang, Yigang

AU - Zhang, Dongsheng

AU - Ashraf, Muhammad

AU - Zhao, Tiemin

AU - Huang, Wei

AU - Ashraf, Atif

AU - Balasubramaniam, Ambikaipakan

PY - 2010/1/1

Y1 - 2010/1/1

N2 - Neuropeptide Y (NPY) induced reentry of differentiated rat neonatal and adult cardiomyocytes into the cell cycle. NPY also induced differentiation of bone marrow-derived mesenchymal stem cells (MSC) into cardiomyocytes following transplantation into infarcted myocardium. Rat neonatal and adult cardiomyocytes were treated in vitro with vehicle, NPY, fibroblast growth factor (FGF; 100 ng/ml), or FGF plus NPY. DNA synthesis, mitosis, and cytokinesis were determined by immunocytochemistry. NPY-induced MSC gene expression, cell migration, tube formation, and endothelial cell differentiation were analyzed. Male rat green fluorescent protein-MSC (2 × 106), pretreated with either vehicle or NPY (10-8 M) for 72 h, were injected into the border zone of the female myocardium following left anterior descending artery ligation. On day 30, heart function was assessed, and hearts were harvested for histological and immunohistochemical analyses. NPY increased 5-bromo-2′-deoxy-uridine incorporation and promoted both cytokinesis and mitosis in rat neonatal and adult myocytes. NPY also upregulated several genes required for mitosis in MSC, including aurora B kinase, FGF-2, cycline A2, eukaryotic initiation factor 4 E, and stromal cell-derived factor-1α. NPY directly induced neonatal and adult cardiomyocyte cell-cycle reentry and enhanced the number of differentiated cardiomyocytes from MSC in the infarcted myocardium, which corresponded to improved cardiac function, reduced fibrosis, ventricular remodeling, and increased angiomyogenesis. It is concluded that a combined treatment of NPY with MSC is a novel approach for cardiac repair.

AB - Neuropeptide Y (NPY) induced reentry of differentiated rat neonatal and adult cardiomyocytes into the cell cycle. NPY also induced differentiation of bone marrow-derived mesenchymal stem cells (MSC) into cardiomyocytes following transplantation into infarcted myocardium. Rat neonatal and adult cardiomyocytes were treated in vitro with vehicle, NPY, fibroblast growth factor (FGF; 100 ng/ml), or FGF plus NPY. DNA synthesis, mitosis, and cytokinesis were determined by immunocytochemistry. NPY-induced MSC gene expression, cell migration, tube formation, and endothelial cell differentiation were analyzed. Male rat green fluorescent protein-MSC (2 × 106), pretreated with either vehicle or NPY (10-8 M) for 72 h, were injected into the border zone of the female myocardium following left anterior descending artery ligation. On day 30, heart function was assessed, and hearts were harvested for histological and immunohistochemical analyses. NPY increased 5-bromo-2′-deoxy-uridine incorporation and promoted both cytokinesis and mitosis in rat neonatal and adult myocytes. NPY also upregulated several genes required for mitosis in MSC, including aurora B kinase, FGF-2, cycline A2, eukaryotic initiation factor 4 E, and stromal cell-derived factor-1α. NPY directly induced neonatal and adult cardiomyocyte cell-cycle reentry and enhanced the number of differentiated cardiomyocytes from MSC in the infarcted myocardium, which corresponded to improved cardiac function, reduced fibrosis, ventricular remodeling, and increased angiomyogenesis. It is concluded that a combined treatment of NPY with MSC is a novel approach for cardiac repair.

UR - http://www.scopus.com/inward/record.url?scp=73549117183&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=73549117183&partnerID=8YFLogxK

U2 - 10.1152/ajpheart.00765.2009

DO - 10.1152/ajpheart.00765.2009

M3 - Article

C2 - 19897711

AN - SCOPUS:73549117183

VL - 298

SP - H275-H286

JO - American Journal of Physiology - Heart and Circulatory Physiology

JF - American Journal of Physiology - Heart and Circulatory Physiology

SN - 0363-6135

IS - 1

ER -