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Pathophysiological mechanism and therapeutic role of S100 proteins in cardiac failure: a systematic review

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Abstract

S100 proteins are a family of highly acidic calcium-binding proteins involved in calcium handling in many tissues and organs. Some of these proteins are highly expressed in cardiac tissue, and an impairment of some specific S100 proteins has been related to heart failure. To check this hypothesis, we decided to review the literature since 2008 until May 2015. According to the studies collected, recovering S100A1 levels may enhance contractile/relaxing performance in heart failure, reverse negative force–frequency relationship, improve contractile reserve, reverse diastolic dysfunction and protect against pro-arrhythmic reductions of sarcoplasmic reticulum calcium. The safety profile of gene therapy was also confirmed. Increased S100B protein levels were related to a worse outcome in chronic heart failure. S100A8/A9 complex plasma levels, as well as other inflammatory biomarkers, were significantly higher in chronic heart failure patients. S100A2 seems to increase both contractile and relaxation performance in animal cardiomyocytes. Otherwise, S100A6 cardiac expression seems to have no effects on contractility. S100A4 KO mice showed reduced cardiac interstitial fibrosis. Data collected encourage a potential prospective application in human. These proteins could be exploited as biomarkers in stadiation and prognosis of chronic heart failure, as well as therapeutic target to rescue failing heart.

Registration details The study protocol has been registered in PROSPERO (http://www.crd.york.ac.uk/PROSPERO/) under registration number CRD42015027932.

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  1. Department of Clinical and Experimental Medicine, Policlinic University of Messina, Via Consolare Valeria n.1, 98125, Messina, Italy

    Egidio Imbalzano, Giuseppe Mandraffino, Sebastiano Quartuccio & Antonino Saitta

  2. School and Division of Allergy and Clinical Immunology, University of Messina, Messina, Italy

    Marco Casciaro & Sebastiano Gangemi

  3. Institute of Applied Sciences and Intelligent Systems (ISASI) - Messina Unit, Messina, Italy

    Sebastiano Gangemi

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  1. Egidio Imbalzano
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Imbalzano, E., Mandraffino, G., Casciaro, M. et al. Pathophysiological mechanism and therapeutic role of S100 proteins in cardiac failure: a systematic review. Heart Fail Rev 21, 463–473 (2016). https://doi.org/10.1007/s10741-016-9529-8

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