S100A1 in human heart failure: lack of recovery following left ventricular assist device support.

We hypothesized that S100A1 is regulated during human hypertrophy and heart failure and that it may be implicated in remodeling after left ventricular assist device. S100A1 is decreased in animal and human heart failure, 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.,We measured S100A1, the sarcoplasmic endoplasmic reticulum Ca(2+)ATPase, phospholamban, and ryanodine receptor proteins, as well as β-adrenergic receptor density in nonfailing, hypertrophied (left ventricular hypertrophy), failing, and failing left ventricular assist device-supported hearts. We determined functional consequences of protein alterations in isolated contracting muscles from the same hearts. S100A1, sarcoplasmic endoplasmic reticulum Ca(2+)ATPase and phospholamban were normal in left ventricular hypertrophy, but decreased in failing hearts, while ryanodine receptor was unchanged in either group. Baseline muscle contraction was not altered in left ventricular hypertrophy or failing hearts. β-Adrenergic receptor and inotropic response were decreased in failing hearts. In failing left ventricular assist device-supported hearts, S100A1 and sarcoplasmic endoplasmic reticulum Ca(2+)ATPase showed no recovery, while phospholamban, β-adrenergic receptor, and the inotropic response fully recovered.,S100A1 and sarcoplasmic endoplasmic reticulum Ca(2+)ATPase, both key Ca(2+)-regulatory proteins, are decreased in human heart failure, and these changes are not reversed after left ventricular assist device. The clinical significance of these findings for cardiac recovery remains to be addressed.