Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET

User menu

  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Journal of Pharmacology and Experimental Therapeutics
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
  • My Cart
Journal of Pharmacology and Experimental Therapeutics

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Visit jpet on Facebook
  • Follow jpet on Twitter
  • Follow jpet on LinkedIn
Research ArticleDrug Discovery and Translational Medicine

Chronic Administration of Small Nonerythropoietic Peptide Sequence of Erythropoietin Effectively Ameliorates the Progression of Postmyocardial Infarction–Dilated Cardiomyopathy

Ismayil Ahmet, Hyun-Jin Tae, Michael Brines, Anthony Cerami, Edward G. Lakatta and Mark I. Talan
Journal of Pharmacology and Experimental Therapeutics June 2013, 345 (3) 446-456; DOI: https://doi.org/10.1124/jpet.113.202945
Ismayil Ahmet
Laboratory of Cardiovascular Sciences, National Institute on Aging/National Institutes of Health, Baltimore, Maryland (I.A., H.-J.T., E.G.L., M.I.T.); and Araim Pharmaceuticals, Ossining, New York (M.B., A.C.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hyun-Jin Tae
Laboratory of Cardiovascular Sciences, National Institute on Aging/National Institutes of Health, Baltimore, Maryland (I.A., H.-J.T., E.G.L., M.I.T.); and Araim Pharmaceuticals, Ossining, New York (M.B., A.C.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michael Brines
Laboratory of Cardiovascular Sciences, National Institute on Aging/National Institutes of Health, Baltimore, Maryland (I.A., H.-J.T., E.G.L., M.I.T.); and Araim Pharmaceuticals, Ossining, New York (M.B., A.C.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Anthony Cerami
Laboratory of Cardiovascular Sciences, National Institute on Aging/National Institutes of Health, Baltimore, Maryland (I.A., H.-J.T., E.G.L., M.I.T.); and Araim Pharmaceuticals, Ossining, New York (M.B., A.C.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Edward G. Lakatta
Laboratory of Cardiovascular Sciences, National Institute on Aging/National Institutes of Health, Baltimore, Maryland (I.A., H.-J.T., E.G.L., M.I.T.); and Araim Pharmaceuticals, Ossining, New York (M.B., A.C.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mark I. Talan
Laboratory of Cardiovascular Sciences, National Institute on Aging/National Institutes of Health, Baltimore, Maryland (I.A., H.-J.T., E.G.L., M.I.T.); and Araim Pharmaceuticals, Ossining, New York (M.B., A.C.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF + SI
  • PDF
Loading

Abstract

The cardioprotective properties of erythropoietin (EPO) in preclinical studies are well documented, but erythropoietic and prothrombotic properties of EPO preclude its use in chronic heart failure (CHF). We tested the effect of long-term treatment with a small peptide sequence within the EPO molecule, helix B surface peptide (HBSP), that possesses tissue-protective, but not erythropoietic properties of EPO, on mortality and cardiac remodeling in postmyocardial infarction–dilated cardiomyopathy in rats. Starting 2 weeks after permanent left coronary artery ligation, rats received i.p. injections of HBSP (60 µg/kg) or saline two times per week for 10 months. Treatment did not elicit an immune response, and did not affect the hematocrit. Compared with untreated rats, HBSP treatment reduced mortality by 50% (P < 0.05). Repeated echocardiography demonstrated remarkable attenuation of left ventricular dilatation (end-diastolic volume: 41 versus 86%; end-systolic volume: 44 versus 135%; P < 0.05), left ventricle functional deterioration (ejection fraction: −4 versus −63%; P < 0.05), and myocardial infarction (MI) expansion (3 versus 38%; P < 0.05). A hemodynamic assessment at study termination demonstrated normal preload independent stroke work (63 ± 5 versus 40 ± 4; P < 0.05) and arterioventricular coupling (1.2 ± 0.2 versus 2.7 ± 0.7; P < 0.05). Histologic analysis revealed reduced apoptosis (P < 0.05) and fibrosis (P < 0.05), increased cardiomyocyte density (P < 0.05), and increased number of cardiomyocytes in myocardium among HBSP-treated rats. The results indicate that HBSP effectively reduces mortality, ameliorates the MI expansion and CHF progression, and preserves systolic reserve in the rat post-MI model. There is also a possibility that HBSP promoted the increase of the myocytes number in the myocardial wall remote from the infarct. Thus, HBSP peptide merits consideration for clinical testing.

Footnotes

    • Received January 4, 2013.
    • Accepted April 10, 2013.
  • I.A. and H.-J.T. contributed equally to this work.

  • This work was fully funded by the Intramural Research Program of the National Institutes of Health [National Institute on Aging]. M.B. and A.C. are employees of Araim Pharmaceuticals, which owns the intellectual property of the peptide.

  • dx.doi.org/10.1124/jpet.113.202945.

  • ↵Embedded ImageThis article has supplemental material available at jpet.aspetjournals.org.

  • U.S. Government work not protected by U.S. copyright
View Full Text

JPET articles become freely available 12 months after publication, and remain freely available for 5 years. 

Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page. 

 

  • Click here for information on institutional subscriptions.
  • Click here for information on individual ASPET membership.

 

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top

In this issue

Journal of Pharmacology and Experimental Therapeutics: 345 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 345, Issue 3
1 Jun 2013
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Editorial Board (PDF)
  • Front Matter (PDF)
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Journal of Pharmacology and Experimental Therapeutics article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Chronic Administration of Small Nonerythropoietic Peptide Sequence of Erythropoietin Effectively Ameliorates the Progression of Postmyocardial Infarction–Dilated Cardiomyopathy
(Your Name) has forwarded a page to you from Journal of Pharmacology and Experimental Therapeutics
(Your Name) thought you would be interested in this article in Journal of Pharmacology and Experimental Therapeutics.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleDrug Discovery and Translational Medicine

A Novel Small-Peptide Treatment in a Rat Model of CHF

Ismayil Ahmet, Hyun-Jin Tae, Michael Brines, Anthony Cerami, Edward G. Lakatta and Mark I. Talan
Journal of Pharmacology and Experimental Therapeutics June 1, 2013, 345 (3) 446-456; DOI: https://doi.org/10.1124/jpet.113.202945

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Research ArticleDrug Discovery and Translational Medicine

A Novel Small-Peptide Treatment in a Rat Model of CHF

Ismayil Ahmet, Hyun-Jin Tae, Michael Brines, Anthony Cerami, Edward G. Lakatta and Mark I. Talan
Journal of Pharmacology and Experimental Therapeutics June 1, 2013, 345 (3) 446-456; DOI: https://doi.org/10.1124/jpet.113.202945
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Introduction
    • Materials and Methods
    • Results
    • Discussion
    • Acknowledgments
    • Authorship Contributions
    • Footnotes
    • Abbreviations
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF + SI
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Blebbistatin scaffold is ideal for drug development
  • Cx43 Activity and Modulation in the Myometrium
  • IKCa channels in muscle hypertrophy
Show more Drug Discovery and Translational Medicine

Similar Articles

  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Fast Forward by date
  • Fast Forward by section
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About JPET
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Drug Metabolism and Disposition
  • Molecular Pharmacology
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0103 (Online)

Copyright © 2021 by the American Society for Pharmacology and Experimental Therapeutics