Abstract
Eukaryotic cells plasma membranes are organized into microdomains
of specialized function such as lipid rafts and caveolae, with a
specific lipid composition highly enriched in cholesterol and glycosphingolipids.
In addition to their role in regulating signal transduction, multiple
functions have been proposed, such as anchorage of receptors, trafficking
of cholesterol, and regulation of permeability. However, an extensive
understanding of their protein composition in human heart, both in
failing and non-failing conditions, is not yet available. Membrane
microdomains were isolated from left ventricular tissue of both failing
(n = 15) and non-failing (n = 15) human hearts. Protein composition
and differential protein expression was explored by comparing series
of 2-D maps and subsequent identification by LC-MS/MS analysis. Data
indicated that heart membrane microdomains are enriched in chaperones,
cytoskeletal-associated proteins, enzymes and protein involved in
signal transduction pathway. In addition, differential protein expression
profile revealed that 30 proteins were specifically up- or down-regulated
in human heart failure membrane microdomains. This study resulted
in the identification of human heart membrane microdomain protein
composition, which was not previously available. Moreover, it allowed
the identification of multiple proteins whose expression is altered
in heart failure, thus opening new perspectives to determine which
role they may play in this disease.
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