Calcium cycling is a major determinant of cardiac function. S100A1 is the most abundant member of the calcium-binding S100 protein family in myocardial tissue. S100A1 interacts with a variety of calcium regulatory proteins such as SERCA2a, ryanodine receptors, L-type calcium channels and Na(+)/Ca(2+) exchangers, thus enhancing calcium cycling. Aside from this major function, S100A1 has an important role in energy balance, myofilament sliding, myofilament calcium sensibility, titin-actin interaction, apoptosis and cardiac remodeling. Apart from its properties regarding cardiomyocytes, S100A1 is also important in vessel relaxation and angiogenesis. S100A1 potentiates cardiac function thus increasing the cardiomyocytes' functional reserve; this is an important feature in heart failure. In fact, S100A1 seems to normalize cardiac function after myocardial infarction. Also, S100A1 is essential in the acute response to adrenergic stimulation. Gene therapy experiments show promising results, although further studies are still needed to reach clinical practice. In this review, we aim to describe the molecular basis and regulatory function of S100A1, exploring its interactions with a myriad of target proteins. We also explore its functional effects on systolic and diastolic function as well as its acute actions. Finally, we discuss S100A1 gene therapy and its progression so far.

Department of Cardiothoracic Surgery Centro Hospitalar São João EPE Porto Portugal

Department of Physiology and Cardiothoracic Surgery Faculty of Medicine University of Porto Porto Portugal

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