Skip to main content
  • American Heart Association
  • Science Volunteer
  • Warning Signs
  • Advanced Search
  • Donate

  • Home
  • About this Journal
    • General Statistics
    • Editorial Board
    • Editors
    • Information for Advertisers
    • Author Reprints
    • Commercial Reprints
    • Customer Service and Ordering Information
  • All Issues
  • Subjects
    • All Subjects
    • Arrhythmia and Electrophysiology
    • Basic, Translational, and Clinical Research
    • Critical Care and Resuscitation
    • Epidemiology, Lifestyle, and Prevention
    • Genetics
    • Heart Failure and Cardiac Disease
    • Hypertension
    • Imaging and Diagnostic Testing
    • Intervention, Surgery, Transplantation
    • Quality and Outcomes
    • Stroke
    • Vascular Disease
  • Browse Features
    • AHA Guidelines and Statements
    • Acknowledgment of Reviewers
    • Clinical Implications
    • Clinical-Pathological Conferences
    • Controversies in Hypertension
    • Editors' Picks
    • Guidelines Debate
    • Meeting Abstracts
    • Recent Advances in Hypertension
    • SPRINT Trial: the Conversation Continues
  • Resources
    • Instructions to Reviewers
    • Instructions for Authors
    • →Article Types
    • → Submission Guidelines
      • Research Guidelines
        • Minimum Information About Microarray Data Experiments (MIAME)
      • Abstract
      • Acknowledgments
      • Clinical Implications (Only by invitation)
      • Conflict(s) of Interest/Disclosure(s) Statement
      • Figure Legends
      • Figures
      • Novelty and Significance: 1) What Is New, 2) What Is Relevant?
      • References
      • Sources of Funding
      • Tables
      • Text
      • Title Page
      • Online/Data Supplement
    • →Tips for Easier Manuscript Submission
    • → General Instructions for Revised Manuscripts
      • Change of Authorship Form
    • → Costs to Authors
    • → Open Access, Repositories, & Author Rights Q&A
    • Permissions to Reprint Figures and Tables
    • Journal Policies
    • Scientific Councils
    • AHA Journals RSS Feeds
    • International Users
    • AHA Newsroom
  • AHA Journals
    • AHA Journals Home
    • Arteriosclerosis, Thrombosis, and Vascular Biology (ATVB)
    • Circulation
    • → Circ: Arrhythmia and Electrophysiology
    • → Circ: Genomic and Precision Medicine
    • → Circ: Cardiovascular Imaging
    • → Circ: Cardiovascular Interventions
    • → Circ: Cardiovascular Quality & Outcomes
    • → Circ: Heart Failure
    • Circulation Research
    • Hypertension
    • Stroke
    • Journal of the American Heart Association
  • Facebook
  • Twitter

  • My alerts
  • Sign In
  • Join

  • Advanced search

Header Publisher Menu

  • American Heart Association
  • Science Volunteer
  • Warning Signs
  • Advanced Search
  • Donate

Hypertension

  • My alerts
  • Sign In
  • Join

  • Facebook
  • Twitter
  • Home
  • About this Journal
    • General Statistics
    • Editorial Board
    • Editors
    • Information for Advertisers
    • Author Reprints
    • Commercial Reprints
    • Customer Service and Ordering Information
  • All Issues
  • Subjects
    • All Subjects
    • Arrhythmia and Electrophysiology
    • Basic, Translational, and Clinical Research
    • Critical Care and Resuscitation
    • Epidemiology, Lifestyle, and Prevention
    • Genetics
    • Heart Failure and Cardiac Disease
    • Hypertension
    • Imaging and Diagnostic Testing
    • Intervention, Surgery, Transplantation
    • Quality and Outcomes
    • Stroke
    • Vascular Disease
  • Browse Features
    • AHA Guidelines and Statements
    • Acknowledgment of Reviewers
    • Clinical Implications
    • Clinical-Pathological Conferences
    • Controversies in Hypertension
    • Editors' Picks
    • Guidelines Debate
    • Meeting Abstracts
    • Recent Advances in Hypertension
    • SPRINT Trial: the Conversation Continues
  • Resources
    • Instructions to Reviewers
    • Instructions for Authors
    • →Article Types
    • → Submission Guidelines
    • →Tips for Easier Manuscript Submission
    • → General Instructions for Revised Manuscripts
    • → Costs to Authors
    • → Open Access, Repositories, & Author Rights Q&A
    • Permissions to Reprint Figures and Tables
    • Journal Policies
    • Scientific Councils
    • AHA Journals RSS Feeds
    • International Users
    • AHA Newsroom
  • AHA Journals
    • AHA Journals Home
    • Arteriosclerosis, Thrombosis, and Vascular Biology (ATVB)
    • Circulation
    • → Circ: Arrhythmia and Electrophysiology
    • → Circ: Genomic and Precision Medicine
    • → Circ: Cardiovascular Imaging
    • → Circ: Cardiovascular Interventions
    • → Circ: Cardiovascular Quality & Outcomes
    • → Circ: Heart Failure
    • Circulation Research
    • Hypertension
    • Stroke
    • Journal of the American Heart Association
Original Article

New Renin Inhibitor VTP-27999 Alters Renin Immunoreactivity and Does Not Unfold Prorenin

Manne Krop, Xifeng Lu, Koen Verdonk, Maarten A.D.H. Schalekamp, Jeanette M.G. van Gool, Brian M. McKeever, Richard Gregg, A.H. Jan Danser
Download PDF
https://doi.org/10.1161/HYPERTENSIONAHA.111.00967
Hypertension. 2013;HYPERTENSIONAHA.111.00967
Originally published March 4, 2013
Manne Krop
From the Department of Internal Medicine, Division of Pharmacology and Vascular Medicine, Erasmus MC, Rotterdam, The Netherlands (M.K., X.L., K.V., M.A.D.H.S., J.M.G.v.G., A.H.J.D.); and Vitae Pharmaceuticals, Fort Washington, PA (B.M.M., R.G.).
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Xifeng Lu
From the Department of Internal Medicine, Division of Pharmacology and Vascular Medicine, Erasmus MC, Rotterdam, The Netherlands (M.K., X.L., K.V., M.A.D.H.S., J.M.G.v.G., A.H.J.D.); and Vitae Pharmaceuticals, Fort Washington, PA (B.M.M., R.G.).
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Koen Verdonk
From the Department of Internal Medicine, Division of Pharmacology and Vascular Medicine, Erasmus MC, Rotterdam, The Netherlands (M.K., X.L., K.V., M.A.D.H.S., J.M.G.v.G., A.H.J.D.); and Vitae Pharmaceuticals, Fort Washington, PA (B.M.M., R.G.).
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Maarten A.D.H. Schalekamp
From the Department of Internal Medicine, Division of Pharmacology and Vascular Medicine, Erasmus MC, Rotterdam, The Netherlands (M.K., X.L., K.V., M.A.D.H.S., J.M.G.v.G., A.H.J.D.); and Vitae Pharmaceuticals, Fort Washington, PA (B.M.M., R.G.).
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jeanette M.G. van Gool
From the Department of Internal Medicine, Division of Pharmacology and Vascular Medicine, Erasmus MC, Rotterdam, The Netherlands (M.K., X.L., K.V., M.A.D.H.S., J.M.G.v.G., A.H.J.D.); and Vitae Pharmaceuticals, Fort Washington, PA (B.M.M., R.G.).
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Brian M. McKeever
From the Department of Internal Medicine, Division of Pharmacology and Vascular Medicine, Erasmus MC, Rotterdam, The Netherlands (M.K., X.L., K.V., M.A.D.H.S., J.M.G.v.G., A.H.J.D.); and Vitae Pharmaceuticals, Fort Washington, PA (B.M.M., R.G.).
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Richard Gregg
From the Department of Internal Medicine, Division of Pharmacology and Vascular Medicine, Erasmus MC, Rotterdam, The Netherlands (M.K., X.L., K.V., M.A.D.H.S., J.M.G.v.G., A.H.J.D.); and Vitae Pharmaceuticals, Fort Washington, PA (B.M.M., R.G.).
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
A.H. Jan Danser
From the Department of Internal Medicine, Division of Pharmacology and Vascular Medicine, Erasmus MC, Rotterdam, The Netherlands (M.K., X.L., K.V., M.A.D.H.S., J.M.G.v.G., A.H.J.D.); and Vitae Pharmaceuticals, Fort Washington, PA (B.M.M., R.G.).
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Supplemental Materials
  • Info & Metrics
  • eLetters

Jump to

  • Article
  • Supplemental Materials
  • Info & Metrics
  • eLetters
Loading

Abstract

Renin inhibitors like aliskiren not only block renin but also bind prorenin, thereby inducing a conformational change (like the change induced by acid) allowing its recognition in a renin-specific assay. Consequently, aliskiren can be used to measure prorenin. VTP-27999 is a new renin inhibitor with an aliskiren-like IC50 and t1/2, and a much higher bioavailability. This study addressed (pro)renin changes during treatment of volunteers with VTP-27999 or aliskiren. Both drugs increased renin immunoreactivity. Treatment of plasma samples from aliskiren-treated subjects with excess aliskiren yielded higher renin immunoreactivity levels, confirming the presence of prorenin. Unexpectedly, this approach did not work in VTP-27999–treated subjects, although an assay detecting the prosegment revealed that their blood still contained prorenin. Subsequent in vitro analysis showed that VTP-27999 increased renin immunoreactivity for a given amount of renin by ≥30% but did not unfold prorenin. Yet, it did bind to acid-activated, intact prorenin and then again increased immunoreactivity in a renin assay. However, no such increase in immunoreactivity was seen when measuring acid-activated prorenin bound to VTP-27999 with a prosegment-directed assay. The VTP-27999–induced rises in renin immunoreactivity could be competitively prevented by aliskiren, and antibody displacement studies revealed a higher affinity of the active site-directed antibodies in the presence of VTP-27999. In conclusion, VTP-27999 increases renin immunoreactivity in renin immunoassays because it affects the affinity of the active site-directed antibody. Combined with its lack of effect on prorenin, these data show that VTP-27999 differs from aliskiren. The clinical relevance of these results needs to be established.

  • conformational changes
  • hypertension
  • prorenin
  • renin
  • renin inhibitor
  • Received December 27, 2012.
  • Revision received February 7, 2013.
  • Accepted February 10, 2013.
  • © 2013 American Heart Association, Inc.
Back to top
Next Article

Current Issue

Hypertension
May 2018, Volume 71, Issue 5
  • Table of Contents
Next Article

Jump to

  • Article
  • Supplemental Materials
  • Info & Metrics
  • eLetters

Article Tools

  • Print
  • Citation Tools
    New Renin Inhibitor VTP-27999 Alters Renin Immunoreactivity and Does Not Unfold Prorenin
    Manne Krop, Xifeng Lu, Koen Verdonk, Maarten A.D.H. Schalekamp, Jeanette M.G. van Gool, Brian M. McKeever, Richard Gregg and A.H. Jan Danser
    Hypertension. 2013;HYPERTENSIONAHA.111.00967, originally published March 4, 2013
    https://doi.org/10.1161/HYPERTENSIONAHA.111.00967

    Citation Manager Formats

    • BibTeX
    • Bookends
    • EasyBib
    • EndNote (tagged)
    • EndNote 8 (xml)
    • Medlars
    • Mendeley
    • Papers
    • RefWorks Tagged
    • Ref Manager
    • RIS
    • Zotero
  • Article Alerts
    Log in to Email Alerts with your email address.
  • Save to my folders

Share this Article

  • Email

    Thank you for your interest in spreading the word on Hypertension.

    NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

    Enter multiple addresses on separate lines or separate them with commas.
    New Renin Inhibitor VTP-27999 Alters Renin Immunoreactivity and Does Not Unfold Prorenin
    (Your Name) has sent you a message from Hypertension
    (Your Name) thought you would like to see the Hypertension web site.
  • Share on Social Media
    New Renin Inhibitor VTP-27999 Alters Renin Immunoreactivity and Does Not Unfold Prorenin
    Manne Krop, Xifeng Lu, Koen Verdonk, Maarten A.D.H. Schalekamp, Jeanette M.G. van Gool, Brian M. McKeever, Richard Gregg and A.H. Jan Danser
    Hypertension. 2013;HYPERTENSIONAHA.111.00967, originally published March 4, 2013
    https://doi.org/10.1161/HYPERTENSIONAHA.111.00967
    del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo

Related Articles

Cited By...

Subjects

  • Intervention, Surgery, Transplantation
    • Pharmacology
  • Basic, Translational, and Clinical Research
    • Clinical Studies

Hypertension

  • About Hypertension
  • Instructions for Authors
  • AHA CME
  • Guidelines and Statements
  • Permissions
  • Journal Policies
  • Email Alerts
  • Open Access Information
  • AHA Journals RSS
  • AHA Newsroom

Editorial Office Address:
7272 Greenville Ave.
Dallas, TX 75231
email: hypertension@heart.org

Information for:
  • Advertisers
  • Subscribers
  • Subscriber Help
  • Institutions / Librarians
  • Institutional Subscriptions FAQ
  • International Users
American Heart Association Learn and Live
National Center
7272 Greenville Ave.
Dallas, TX 75231

Customer Service

  • 1-800-AHA-USA-1
  • 1-800-242-8721
  • Local Info
  • Contact Us

About Us

Our mission is to build healthier lives, free of cardiovascular diseases and stroke. That single purpose drives all we do. The need for our work is beyond question. Find Out More about the American Heart Association

  • Careers
  • SHOP
  • Latest Heart and Stroke News
  • AHA/ASA Media Newsroom

Our Sites

  • American Heart Association
  • American Stroke Association
  • For Professionals
  • More Sites

Take Action

  • Advocate
  • Donate
  • Planned Giving
  • Volunteer

Online Communities

  • AFib Support
  • Garden Community
  • Patient Support Network
  • Professional Online Network

Follow Us:

  • Follow Circulation on Twitter
  • Visit Circulation on Facebook
  • Follow Circulation on Google Plus
  • Follow Circulation on Instagram
  • Follow Circulation on Pinterest
  • Follow Circulation on YouTube
  • Rss Feeds
  • Privacy Policy
  • Copyright
  • Ethics Policy
  • Conflict of Interest Policy
  • Linking Policy
  • Diversity
  • Careers

©2018 American Heart Association, Inc. All rights reserved. Unauthorized use prohibited. The American Heart Association is a qualified 501(c)(3) tax-exempt organization.
*Red Dress™ DHHS, Go Red™ AHA; National Wear Red Day ® is a registered trademark.

  • PUTTING PATIENTS FIRST National Health Council Standards of Excellence Certification Program
  • BBB Accredited Charity
  • Comodo Secured