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Hypercholesterolaemic serum increases the permeability of endothelial cells through zonula occludens-1 with phosphatidylinositol 3-kinase signaling pathway. 2009

Chang Bian, and Geng Xu, and Jianan Wang, and Ji Ma, and Meixiang Xiang, and Peng Chen
Department of Cardiology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.

OBJECTIVE Hypercholesterolemia and tight junctions play important roles in atherosclerosis. But the relationship between these two factors is unclear. In the present study, we investigated whether hypercholesterolemic serum could change the permeability of endothelial cells through altering expression and/or distribution of tight junction protein zonula occludens-1 (ZO-1). Phosphatidylinositol 3-kinase (PI3K) signaling pathway was also examined. METHODS Cultured endothelial cells were treated with different concentration levels of hypercholesterolemic serum. The expression and distribution of ZO-1, the permeability of cultured cells and the involvement of PI3K signaling pathway were measured by various methods. RESULTS In the present study, we found that hypercholesterolemic serum could not change the expression of ZO-1 either in mRNA or protein level. However, hypercholesterolemic serum could change the distribution of ZO-1 in cultured endothelial cells, and increase the permeability with a dose-dependent manner. When PI3K specific inhibitor wortmannin was used, the effects induced by hypercholesterolemic serum could be partly reversed. The role of PI3K signaling pathway was further confirmed by PI3K activity assay. CONCLUSIONS Our results suggested that although hypercholesterolemic serum could not change the expression of ZO-1, it could change the distribution and increase the permeability in endothelial cells through PI3K signaling pathway.

UI MeSH Term Description Entries
D008565 Membrane Proteins Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. Cell Membrane Protein,Cell Membrane Proteins,Cell Surface Protein,Cell Surface Proteins,Integral Membrane Proteins,Membrane-Associated Protein,Surface Protein,Surface Proteins,Integral Membrane Protein,Membrane Protein,Membrane-Associated Proteins,Membrane Associated Protein,Membrane Associated Proteins,Membrane Protein, Cell,Membrane Protein, Integral,Membrane Proteins, Integral,Protein, Cell Membrane,Protein, Cell Surface,Protein, Integral Membrane,Protein, Membrane,Protein, Membrane-Associated,Protein, Surface,Proteins, Cell Membrane,Proteins, Cell Surface,Proteins, Integral Membrane,Proteins, Membrane,Proteins, Membrane-Associated,Proteins, Surface,Surface Protein, Cell
D010750 Phosphoproteins Phosphoprotein
D011817 Rabbits A burrowing plant-eating mammal with hind limbs that are longer than its fore limbs. It belongs to the family Leporidae of the order Lagomorpha, and in contrast to hares, possesses 22 instead of 24 pairs of chromosomes. Belgian Hare,New Zealand Rabbit,New Zealand Rabbits,New Zealand White Rabbit,Rabbit,Rabbit, Domestic,Chinchilla Rabbits,NZW Rabbits,New Zealand White Rabbits,Oryctolagus cuniculus,Chinchilla Rabbit,Domestic Rabbit,Domestic Rabbits,Hare, Belgian,NZW Rabbit,Rabbit, Chinchilla,Rabbit, NZW,Rabbit, New Zealand,Rabbits, Chinchilla,Rabbits, Domestic,Rabbits, NZW,Rabbits, New Zealand,Zealand Rabbit, New,Zealand Rabbits, New,cuniculus, Oryctolagus
D002463 Cell Membrane Permeability A quality of cell membranes which permits the passage of solvents and solutes into and out of cells. Permeability, Cell Membrane
D002784 Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Epicholesterol
D004041 Dietary Fats Fats present in food, especially in animal products such as meat, meat products, butter, ghee. They are present in lower amounts in nuts, seeds, and avocados. Fats, Dietary,Dietary Fat,Fat, Dietary
D005786 Gene Expression Regulation Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation. Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D006937 Hypercholesterolemia A condition with abnormally high levels of CHOLESTEROL in the blood. It is defined as a cholesterol value exceeding the 95th percentile for the population. Hypercholesteremia,Elevated Cholesterol,High Cholesterol Levels,Cholesterol Level, High,Cholesterol Levels, High,Cholesterol, Elevated,Cholesterols, Elevated,Elevated Cholesterols,High Cholesterol Level,Hypercholesteremias,Hypercholesterolemias,Level, High Cholesterol,Levels, High Cholesterol
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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