Immunolocalization of annexins IV, V and VI in the failing and non-failing human heart.

UNLABELLED The failing human heart is characterized by changes in the expression and function of proteins involved in intracellular Ca2+ cycling, resulting in altered Ca2+ transients and impaired contractile properties of cardiac muscle. The role of the cardiac annexins in this process remains unclear. Annexins may play a role in the regulation of Ca2+ pumps and exchangers on the sarcolemma, and have been shown to be altered in some cardiac disease states. OBJECTIVE The goal of this study was to compare the immunolocalization and expression of annexins IV, V and VI in failing and non-failing human hearts. METHODS We used immunostaining to identify the subcellular location of annexins IV, V and VI proteins within the myocardial cell, and Western blot analysis to quantify the proteins in the same hearts. RESULTS Annexin IV showed a cytoplasmic distribution in both failing and non-failing human heart cells. Annexin V was localized at the z-line, around lipofuscin granules, and in the cytosol in the non-failing heart cells. Annexin VI was localized at the sarcolemma and intercalated disc. Protein levels of annexins IV and V were up-regulated in failing human hearts, while the expression of annexin VI was unchanged. CONCLUSIONS Alterations in the intracellular localization of annexins, along with up-regulation of annexins IV and V in the failing human heart cells, suggests differential regulation of these Ca2+ regulatory proteins during heart failure.