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

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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.

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Authors and Affiliations

  1. Division of Cardiac Surgery, University of Verona Medical School, Verona, Italy

    Francesco Onorati, Francesco Santini, Maddalena Tessari, Alessandro Mazzucco & Giuseppe Faggian

  2. Division of Cardiology, Veteran Affairs Ann Harbor, University of Michigan, Ann Arbor, MI, USA

    Carol Chen-Scarabelli

  3. Medical Molecular Biology Unit, University College London, London, UK

    Richard Knight & Anastasis Stephanou

  4. Mount Sinai Medical Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Bibhu Mohanti, Annapoorna Kini, Jagat Narula & Tiziano Scarabelli

  5. Center for Heart and Vessel Preclinical Studies, St John Hospital and Medical Center, Wayne State University Medical School, Detroit, MI, USA

    Louis Saravolatz & Tiziano Scarabelli

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  1. Francesco Onorati
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Correspondence to Tiziano Scarabelli.

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Onorati, F., Chen-Scarabelli, C., Knight, R. et al. Targeting Urocortin Signaling Pathways to Enhance Cardioprotection: Is It Time to Move from Bench to Bedside?. Cardiovasc Drugs Ther 27, 451–463 (2013). https://doi.org/10.1007/s10557-013-6468-7

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