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

The failing human heart is characterized by changes in the expression and f unction of proteins involved in intracellular Ca2+ cycling, resulting in al tered Ca2+ transients and impaired contractile properties of cardiac muscle . The role of the cardiac annexins in this process remains unclear. Annexin s may play a role in the regulation of Ca2+ pumps and exchangers on the sar colemma, 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 a nnexins IV,V and VI proteins within the myocardial cell, and Western blot a nalysis to quantify the proteins in the same hearts. Results: Annexin IV sh owed 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 annex in VI was unchanged. Conclusions: Alterations in the intracellular localiza tion of annexins, along with up-regulation of annexins IV and V in the fail ing human heart cells, suggests differential regulation of these Ca2+ regul atory proteins during heart failure. (C) 2000 Elsevier Science B.V. All rig hts reserved.