Natural Heart Regeneration in a Neonatal Rat Myocardial Infarction Model

Hanjay Wang; Michael  J. Paulsen; Camille  E. Hironaka; Hye  Sook Shin; Justin  M. Farry; Akshara  D. Thakore; Jinsuh Jung; Haley  J. Lucian; Anahita Eskandari; Shreya Anilkumar; Matthew  A. Wu; Mariana  C. Cabatu; Amanda  N. Steele; Lyndsay  M. Stapleton; Yuanjia Zhu; Y.  Joseph Woo

doi:10.3390/cells9010229

Cells (Jan 2020)

Natural Heart Regeneration in a Neonatal Rat Myocardial Infarction Model

Hanjay Wang,
Michael J. Paulsen,
Camille E. Hironaka,
Hye Sook Shin,
Justin M. Farry,
Akshara D. Thakore,
Jinsuh Jung,
Haley J. Lucian,
Anahita Eskandari,
Shreya Anilkumar,
Matthew A. Wu,
Mariana C. Cabatu,
Amanda N. Steele,
Lyndsay M. Stapleton,
Yuanjia Zhu,
Y. Joseph Woo

Affiliations

Hanjay Wang: Department of Cardiothoracic Surgery, Stanford University, Stanford, CA 94305, USA
Michael J. Paulsen: Department of Cardiothoracic Surgery, Stanford University, Stanford, CA 94305, USA
Camille E. Hironaka: Department of Cardiothoracic Surgery, Stanford University, Stanford, CA 94305, USA
Hye Sook Shin: Department of Cardiothoracic Surgery, Stanford University, Stanford, CA 94305, USA
Justin M. Farry: Department of Cardiothoracic Surgery, Stanford University, Stanford, CA 94305, USA
Akshara D. Thakore: Department of Cardiothoracic Surgery, Stanford University, Stanford, CA 94305, USA
Jinsuh Jung: Department of Cardiothoracic Surgery, Stanford University, Stanford, CA 94305, USA
Haley J. Lucian: Department of Cardiothoracic Surgery, Stanford University, Stanford, CA 94305, USA
Anahita Eskandari: Department of Cardiothoracic Surgery, Stanford University, Stanford, CA 94305, USA
Shreya Anilkumar: Department of Cardiothoracic Surgery, Stanford University, Stanford, CA 94305, USA
Matthew A. Wu: Department of Cardiothoracic Surgery, Stanford University, Stanford, CA 94305, USA
Mariana C. Cabatu: Department of Cardiothoracic Surgery, Stanford University, Stanford, CA 94305, USA
Amanda N. Steele: Department of Cardiothoracic Surgery, Stanford University, Stanford, CA 94305, USA
Lyndsay M. Stapleton: Department of Cardiothoracic Surgery, Stanford University, Stanford, CA 94305, USA
Yuanjia Zhu: Department of Cardiothoracic Surgery, Stanford University, Stanford, CA 94305, USA
Y. Joseph Woo: Department of Cardiothoracic Surgery, Stanford University, Stanford, CA 94305, USA

DOI: https://doi.org/10.3390/cells9010229
Journal volume & issue: Vol. 9, no. 1
p. 229

Abstract

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Newborn mice and piglets exhibit natural heart regeneration after myocardial infarction (MI). Discovering other mammals with this ability would provide evidence that neonatal cardiac regeneration after MI may be a conserved phenotype, which if activated in adults could open new options for treating ischemic cardiomyopathy in humans. Here, we hypothesized that newborn rats undergo natural heart regeneration after MI. Using a neonatal rat MI model, we performed left anterior descending coronary artery ligation or sham surgery in one-day-old rats under hypothermic circulatory arrest (n = 74). Operative survival was 97.3%. At 1 day post-surgery, rats in the MI group exhibited significantly reduced ejection fraction (EF) compared to shams (87.1% vs. 53.0%, p < 0.0001). At 3 weeks post-surgery, rats in the sham and MI groups demonstrated no difference in EF (71.1% vs. 69.2%, respectively, p = 0.2511), left ventricular wall thickness (p = 0.9458), or chamber diameter (p = 0.7801). Masson’s trichome and picrosirius red staining revealed minimal collagen scar after MI. Increased numbers of cardiomyocytes positive for 5-ethynyl-2′-deoxyuridine (p = 0.0072), Ki-67 (p = 0.0340), and aurora B kinase (p = 0.0430) were observed within the peri-infarct region after MI, indicating ischemia-induced cardiomyocyte proliferation. Overall, we present a neonatal rat MI model and demonstrate that newborn rats are capable of endogenous neocardiomyogenesis after MI.

Published in Cells

ISSN: 2073-4409 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Biology (General): Cytology
Website: https://www.mdpi.com/journal/cells

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