Search

Background: Membrane microdomains represent dynamic membrane nano-assemblies enriched in signaling molecules suggesting their active involvement in not only physiological but also pathological molecular processes. The hyperlipidemic stress is a major risk factor of atherosclerosis, but its exact mechanisms of action at the membrane microdomains level remain elusive. The aim of the present study was to determine whether membrane-cytoskeleton proteome in the pulmonary tissue could be modulated by the hyperlipidemic stress, a major risk factor of atherosclerosis. Results: High resolution mass spectrometry based proteomics analysis was performed for detergent resistant membrane microdomains isolated from lung homogenates of control, ApoE deficient and statin treated ApoE deficient mice. The findings of the study allowed the identification with high confidence of 1925 proteins, 291 of which were found significantly altered by the modified genetic background, by the statin treatment or both conditions. Principal component analysis revealed a proximal partitioning of the biological replicates, but also a distinct spatial scattering of the sample groups, highlighting different quantitative profiles. The statistical significant over-representation of Regulation of actin cytoskeleton, Focal adhesion and Adherens junction Kyoto Encyclopedia of Genes and Genomes signaling pathways was demonstrated through bioinformatics analysis. The three inter-relation maps comprised 29 of regulated proteins, proving membrane-cytoskeleton coupling targeting and alteration by hyperlipidemia and/or statin treatment. Conclusions: The findings of the study allowed the identification with high confidence of the main proteins modulated by the hyperlipidemic stress involved in the actin-dependent pathways. Our study provides the basis for future work probing how the protein activities at the membrane-cytoskeleton interface are dependent upon genetic induced hyperlipidemia. [ABSTRACT FROM AUTHOR]

Hyperlipidemia is a common risk factor for the initiation and progression of cardiovascular diseases, affecting complex signaling pathways and leading to a fatal outcome in the most severe events. It has been proven that the non-ionic detergent insoluble membrane microdomains are enriched in signaling molecules, taking part in various essential physiological but also pathological processes. The aim of the present study was to demonstrate the comparable alteration of membrane signaling pathways produced by either genetically or diet induced hyperlipidemic stress. Using two established hyperlipidemic laboratory animal models, the ApoE deficient mouse and the diet induced hyperlipemic Golden Syrian hamster, we have analyzed the proteomic profile of detergent resistant membrane microdomains in hyperlipidemic and statin treatment conditions versus the appropriate control states. Employing latest generation liquid chromatographic and mass spectrometric approaches followed by specialized software analysis allowed us to discover with high degree of confidence protein molecules' inter-relation maps affected by hyperlipidemia and statin treatment such as leukocyte transendothelial migration, tight junctions, phagosomal signaling, common to both types of organisms. However, the different methods to induce the high fat stress revealed uniquely altered signaling pathways in antigen processing and presentation , citrate cycle , extracellular matrix-receptor interaction , adherence junction and focal adhesion in one or the other organism. [ABSTRACT FROM AUTHOR]