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

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. (C) 2000 Elsevier Science B.V. All rights reserved.