プラーク内血管新生に及ぼすカテキンの影響 : 培養内皮細胞を用いた検討

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Blood vessel formation after birth (angiogenesis), occurs within ischemic lesion to salvage jeopardized hypoxic cells. It also occurs within atherosclerotic plaques in which inflammatory cells are releasing angiogenic factors. However, angiogenesis in atherosclerotic plaque increases the vulnerability of plaque and the incidence of symptomatic atherosclerotic diseases. Therefore, the inhibition of angiogenesis in plaque could prevent unstabilization of the plaque and the resulting ischemic disease. Vascular endothelial growth factor (VEGF) is one of key regulators of angiogenesis. Lysophosphatidylcholine (LysoPC) and sphingosine - 1 - phosphate (SIP), which are contained in low density lipoprotein (LDL) and oxidized LDL, are two major modifiers of VEGF action in atherosclerotic plaque. We applied these substances on cultured bovine vascular endothelial cells (BAEC) to mimic angiogenesis in atherosclerosis in vitro, and examined whether epigallocatechin - 3 - gallate (EGCG), the major green tea catechin, has inhibitory effects on plaque angiogenesis. The effects of catechins were tested in three models of angiogenesis, namely, migration, growth and tube formation of BAEC. EGCG inhibited angiogenesis in vitro in Boyden chamber assay for migration step, cell counting assay for growth step and matrigel assay for tube formation step at concentration ranging from 1 to 50μM. Therefore, EGCG could stabilize atherosclerotic plaques by inhibiting angiogenesis and prevent them from rupture.

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