Cardiovascular Drugs and Therapy

, Volume 27, Issue 5, pp 451–463 | Cite as

Targeting Urocortin Signaling Pathways to Enhance Cardioprotection: Is It Time to Move from Bench to Bedside?

  • Francesco Onorati
  • Carol Chen-Scarabelli
  • Richard Knight
  • Anastasis Stephanou
  • Bibhu Mohanti
  • Francesco Santini
  • Maddalena Tessari
  • Annapoorna Kini
  • Jagat Narula
  • Louis Saravolatz
  • Alessandro Mazzucco
  • Tiziano Scarabelli
  • Giuseppe Faggian
REVIEW ARTICLE

Abstract

Despite the exponential growth in medical knowledge, cardiovascular diseases (CVDs) contribute to more than one-third of worldwide morbidity and mortality. A range of therapies already exist for established CVDs, although there is significant interest in further understanding their pathogenesis. The urocortins (Ucns) are peptide members of the corticotrophin-releasing factor family, a group of evolutionary conserved peptides with homologues in fish, amphibians and mammals and considered to play a pivotal role in energy homeostasis and local tissue repair. A number of preclinical studies in vitro, in-vivo and ex-vivo have defined a multifaceted effect of Ucns on the cardiovascular system. Different G-protein coupled signaling and protein-kinase pathways have been shown to be activated by Ucns, together with different transcriptional and translational effects, all of which preferentially converge on the mitochondria, where the modulation of apoptosis is considered their principal action. It has been demonstrated in experimental models, and consequentially suggested in human diseases, that Ucn-mediated inhibition of apoptosis can be exploited for the improvement of both therapeutic and preventative strategies against CVDs. Specifically, some unavoidable iatrogenic ischemia/reperfusion (I/R) injuries, e.g. during cardiac surgery or percutaneous coronary angioplasty, may greatly benefit from the anti-apoptotic effect of Ucns. However, few studies on the topic have been employed in humans to date. Therefore, this review will focus on the different intra-cellular mechanisms of action of Urocortins, and detail the different Ucn-mediated pathways identified so far. It will also highlight the limited evidence already existing in human clinical and surgical settings, as well as emphasize the potential uses of Ucns in human cardiac pathology.

Keywords

Urocortin Cardioprotection Ischemia reperfusion injury Mitochondria Apoptosis Cardioplegia 

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Francesco Onorati
    • 1
  • Carol Chen-Scarabelli
    • 2
  • Richard Knight
    • 3
  • Anastasis Stephanou
    • 3
  • Bibhu Mohanti
    • 4
  • Francesco Santini
    • 1
  • Maddalena Tessari
    • 1
  • Annapoorna Kini
    • 4
  • Jagat Narula
    • 4
  • Louis Saravolatz
    • 5
  • Alessandro Mazzucco
    • 1
  • Tiziano Scarabelli
    • 4
    • 5
  • Giuseppe Faggian
    • 1
  1. 1.Division of Cardiac SurgeryUniversity of Verona Medical SchoolVeronaItaly
  2. 2.Division of Cardiology, Veteran Affairs Ann HarborUniversity of MichiganAnn ArborUSA
  3. 3.Medical Molecular Biology UnitUniversity College LondonLondonUK
  4. 4.Mount Sinai Medical CenterIcahn School of Medicine at Mount SinaiNew YorkUSA
  5. 5.Center for Heart and Vessel Preclinical Studies, St John Hospital and Medical CenterWayne State University Medical SchoolDetroitUSA

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