Phenotypic alterations in human saphenous vein culture induced by tumor necrosis factor-alpha and lipoproteins: a preliminary development of an initial atherosclerotic plaque model

Atherosclerosis is a chronic progressive inflammatory disease of blood vessels particularly the arteries. The development of atherosclerotic plaques or atherogenesis is a complex process that is influenced by cardiovascular risk factors such as vascular inflammation and dyslipidemia. This study demo...

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Published in:	Lipids in health and disease Vol. 12; no. 1; p. 132
Main Authors:	Prasongsukarn, Kriengchai, Chaisri, Urai, Chartburus, Peenutchanee, Wetchabut, Kamolwan, Benjathummarak, Surachet, Khachansaksumet, Vasant, Maneerat, Yaowapa
Format:	Journal Article
Language:	English
Published:	England BioMed Central Ltd 08-09-2013 BioMed Central
Subjects:	Analysis Animals Atherosclerotic plaque Biomarkers - metabolism California Cardiovascular diseases Care and treatment Cattle Culture Media Development and progression Diagnosis Diseases Estradiol - pharmacology Estrogen Gene Expression Gene Expression Profiling Health aspects Humans Lipoproteins, LDL - pharmacology Low density lipoproteins Male Medical research Models, Biological Muscular system Nitric oxide Phenotype Plaque, Atherosclerotic - chemically induced Plaque, Atherosclerotic - genetics Plaque, Atherosclerotic - metabolism Plaque, Atherosclerotic - pathology Risk factors RNA Saphenous Vein - drug effects Saphenous Vein - metabolism Saphenous Vein - pathology Studies Tissue Culture Techniques Tumor necrosis factor Tumor Necrosis Factor-alpha - pharmacology Veins & arteries California Bangkok Thailand
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Summary:	Atherosclerosis is a chronic progressive inflammatory disease of blood vessels particularly the arteries. The development of atherosclerotic plaques or atherogenesis is a complex process that is influenced by cardiovascular risk factors such as vascular inflammation and dyslipidemia. This study demonstrates the ability of tumor necrosis factor-alpha (TNF-α) and low density lipoproteins (LDL) to induce atherosclerotic plaque in human saphenous vein (HSV) organ culture. Normal HSV segments, from male patients who had coronary bypass graft, were cultured in DMEM containing 5% heat inactivated fetal bovine serum. TNF-α (5 ng/ml) was applied in combination with native LDL (nLDL) or oxidized LDL (oxLDL) at the dose of 50 μg/ml for 14 days. The phenotypic changes of the organ cultures characteristic of initial atherosclerotic plaques were evaluated. The effect of anti-atherogenic agent, 17-β estradiol (E2), was also determined. Histologic, histomorphometric, and immunohistochemical examinations revealed that HSV rings stimulated with TNF-α + nLDL or TNF-α + oxLDL can exhibit the essential morphological features of atherogenesis, including fibrous cap formation, cholesterol clefts, evident thickening of the intimal layer, increased proliferation of smooth muscle cells (SMC) and migration to the subendothelial layer, significant SMC foam cell formation, and increased expression of adhesion molecules in the vascular wall. Addition of E2 (50 nM) to the culture significantly modulated the critical changes. Consistently, mRNA profiling of the HSV model revealed that 50 of 84 genes of atherosclerosis were up-regulated. Phenotypic changes characteristic of the initial development of atherosclerotic plaques can be induced in HSV organ culture.
ISSN:	1476-511X 1476-511X
DOI:	10.1186/1476-511x-12-132