S100A1 in Human Heart Failure: Lack of Recovery Following LVAD Support

Background —We hypothesized that S100A1 is regulated during human hypertrophy and heart failure (HF), and that it may be implicated in remodeling after left ventricular assist device (LVAD). S100A1 is decreased in animal and human HF and restoration produces functional recovery in animal models and in failing human myocytes. With the potential for gene therapy, it is important to carefully explore human cardiac S100A1 regulation and its role in remodeling. Methods and Results —We measured S100A1, the sarcoplasmic endoplasmic reticulum Ca2+ATPase (SERCA), phospholamban (PLB) and ryanodine receptor (RYR) proteins as well as β-adrenergic receptor density (β-AR) in non-failing (NF), hypertrophied (LVH), failing (F) and failing LVAD-supported (F+LVAD) hearts. We determined functional consequences of protein alterations in isolated contracting muscles from the same hearts. S100A1, SERCA and PLB were normal in LVH, but decreased in F, while RYR was unchanged in either group. Baseline muscle contraction was not altered in LVH or F. β-AR and inotropic response were decreased in F. In F+LVAD, S100A1 and SERCA showed no recovery, while PLB, β-AR and the inotropic response fully recovered. Conclusions —S100A1 and SERCA, both key Ca2+-regulatory proteins, are decreased in human HF and these changes are not reversed following LVAD. The clinical significance of these findings for cardiac recovery remains to be addressed.