Am J Cardiovasc Dis 2012;2(1):1-11
Original Article
Profound influence of LDL oxidative status and monocyte co-cultures on
baboon endothelial activation
Juan Xiao, Vida Hondara, Xing Li Wang, John L. VandeBerg, Qiang Shi
Southwest National Primate Research Center; Texas Biomedical Research Institute, P.O. Box 760549, San Antonio, TX
78245-0549, USA; Cardiothoracic Research Laboratory, Texas Heart Institute, Baylor College of Medicine, Houston, TX
77030-2604, USA; JX: Present address: Department of Endocrinology, Qilu Hospital, Shandong University, 107 Wen Hua
Xi Lu, Jinan, Shandong, China
Received August 30, 2011; accepted September 23, 2011; Epub December 15, 2011; Published January 1, 2012
Abstract: Objective: To investigate how increased LDL levels interact with endothelial cells by using well-defined LDL
preparations to limit experimental biases caused by heterogeneity of LDL preparations. Methods: We pooled LDL from
multiple subjects and prepared several types of LDL from a single source. Then we observed their effects on cultured
endothelial cells with and without monocyte co-culture. Results: Native and minimally oxidized LDL did not cause
significant cell death under most circumstances, and did not up-regulate cellular adhesion molecule (CAM) expression.
Native LDL did result in significant increases of MCP-1 release in five of eight subjects. However, extensively oxidized LDL
caused a significant amount of cell death and dramatically decreased MCP-1 secretion. Minimally oxidized LDL elicited a
mixed response pattern, with a great deal of variation among subjects. When endothelial cells were co-cultured with
monocytes and treated with native LDL, significant up-regulation of CAMs was detected after 24 hours of exposure. Up-
regulation was not seen in any treatment group that contained either native LDL or monocytes only, indicating a synergistic
effect of LDL and monocytes on endothelial cells. Incubation of cultured monocytes with native LDL also resulted in TNF-
and IL-1 release in a dosage- and time-dependent manner. Neutralization of both TNF- and IL-1 by 10 g/mL
polyclonal antibodies inhibited the up-regulation of CAMs. Conclusion: Our results suggest that varying extents of oxidative
modification of LDL lead to fundamentally different cytological effects and that native LDL exhibits greater endothelial
activation capacity when it interactively cooperates with monocytes. (AJCD1108005).
Keywords: LDL characterization, endothelial activation, oxidized LDL, co-culture , monocyte activation, large animal model
Full Text PDF
Address all correspondence to:
Dr. Qiang Shi
Southwest National Primate Research Center
at the Texas Biomedical Research Institute
P. O. Box 760549, San Antonio, TX 78245-0549, USA.
Tel: (210) 258-9703; Fax: (210) 258-9796
E-mail: qshi@txbiomedgenetics.org
Original Article
Profound influence of LDL oxidative status and monocyte co-cultures on
baboon endothelial activation
Juan Xiao, Vida Hondara, Xing Li Wang, John L. VandeBerg, Qiang Shi
Southwest National Primate Research Center; Texas Biomedical Research Institute, P.O. Box 760549, San Antonio, TX
78245-0549, USA; Cardiothoracic Research Laboratory, Texas Heart Institute, Baylor College of Medicine, Houston, TX
77030-2604, USA; JX: Present address: Department of Endocrinology, Qilu Hospital, Shandong University, 107 Wen Hua
Xi Lu, Jinan, Shandong, China
Received August 30, 2011; accepted September 23, 2011; Epub December 15, 2011; Published January 1, 2012
Abstract: Objective: To investigate how increased LDL levels interact with endothelial cells by using well-defined LDL
preparations to limit experimental biases caused by heterogeneity of LDL preparations. Methods: We pooled LDL from
multiple subjects and prepared several types of LDL from a single source. Then we observed their effects on cultured
endothelial cells with and without monocyte co-culture. Results: Native and minimally oxidized LDL did not cause
significant cell death under most circumstances, and did not up-regulate cellular adhesion molecule (CAM) expression.
Native LDL did result in significant increases of MCP-1 release in five of eight subjects. However, extensively oxidized LDL
caused a significant amount of cell death and dramatically decreased MCP-1 secretion. Minimally oxidized LDL elicited a
mixed response pattern, with a great deal of variation among subjects. When endothelial cells were co-cultured with
monocytes and treated with native LDL, significant up-regulation of CAMs was detected after 24 hours of exposure. Up-
regulation was not seen in any treatment group that contained either native LDL or monocytes only, indicating a synergistic
effect of LDL and monocytes on endothelial cells. Incubation of cultured monocytes with native LDL also resulted in TNF-
and IL-1 release in a dosage- and time-dependent manner. Neutralization of both TNF- and IL-1 by 10 g/mL
polyclonal antibodies inhibited the up-regulation of CAMs. Conclusion: Our results suggest that varying extents of oxidative
modification of LDL lead to fundamentally different cytological effects and that native LDL exhibits greater endothelial
activation capacity when it interactively cooperates with monocytes. (AJCD1108005).
Keywords: LDL characterization, endothelial activation, oxidized LDL, co-culture , monocyte activation, large animal model
Full Text PDF
Address all correspondence to:
Dr. Qiang Shi
Southwest National Primate Research Center
at the Texas Biomedical Research Institute
P. O. Box 760549, San Antonio, TX 78245-0549, USA.
Tel: (210) 258-9703; Fax: (210) 258-9796
E-mail: qshi@txbiomedgenetics.org
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