Inhibition of intimal hyperplasia by caffeic acid-impregnated bio-degradable PLGA

Abstract

[한글]

Caffeic acid (MLB)는 단삼으로부터 추출된 천연물질로서, 혈관 확장 효과, 혈압 저하 효과로 예로부터 한약재로 널리쓰여 왔다. 혈관평활근세포와 정맥내피세포의 이동, 증식은 여러 가지 혈관재협착 중 혈관내막 과형성증에 중요한 역할을 한다. Caffeic acid (MLB)가 혈관평활근세포와 혈관내피세포의 이동, 증식에 미치는 영향에 대해 확인하였다. 혈관평활근세포의 증식 및 이동은 저해 했고, 그 인자인 Integrin b1, FAK, MMP-2의 분비량을 저해시켰지만, 오히려 혈관내피세포에서는 증식과 이동에 영향을 미치지 않거나 다소 활성화 시켰고, 그 인자인 Integrin b1, FAK, MMP-2의 분비량도 영향을 주지 않거나 다소 활성화 시켰다. 이와 같은 결과를 확인한 후 이런 효과를 가진 Caffeic acid (MLB)를 혼합한 생분해성 PLGA에서도 혈관평활근세포와 혈관내피세포에 미치는 영향을 확인해 보았다. Caffeic acid (MLB)를 포함하는 생분해성 PLGA에서도 앞선 in vitro tissue culture 결과와 같이 혈관평활근세포의 증식을 억제했지만, 혈관내피세포는 활성화 시켰다. 결론적으로, 이러한 일련의 결과들은 Caffeic acid (MLB) 직, 간접적인 경로 모두를 통해 혈관 내막과형성증을 억제하는 효과가 있음을 제시하였다. 이렇게 만들어진 결과물을 조직공학의 적용가능성의 확인 및인공혈관이나 스텐트로써의 가능성을 확인하였다.

[영문]Vascular smooth muscle cell (VSMC) proliferation and migration plays an important role in normal angiogenesis and is relevant to disease-related vascular remodeling in conditions such as brain arteriovenous malformations, pulmonary hypertension, arteriosclerosis, and restenosis after angioplasty. VSMCs proliferation and migration appears to be multifactorial and is thought to involve autocrine and paracrine stimulation by growth factors such as platelet-derived growth factor released by injured endothelial cells (ECs), SMCs, and inflammatory cells. VSMCs proliferation and migration are reactive oxygen species-dependent. Danshen is a representative oriental medicine used for the treatment of vascular disease. Previously, reported that magnesium lithospermate B, an active component of Danshen, is a potent antioxidant. Thus we investigated the therapeutic potential of magnesium lithospermate B in intimal hyperplasia after carotid artery injury with its effects on the migration factor for stimulating VSMCs proliferation and migration in vitro. In this study, Our results demonstrated that magnesium lithospermate B directly reduced proliferation and migration induced intracellular reactive in VSMCs. But did not affected migration induced HUVECs. We were used Poly (D,L-latic-co-glycolic acid) (PLGA) has been used as the artificial scaffold for blood vessel formation. In order to hinder vascular smooth muscle cell (VSMC) angiogenesis, new scaffold design method of loading magnesium lithospermate B (MLB) on PLGA film was introduced. PLGA and MLB were dissolved in acetone and film-shape scaffold was manufactured. intimal hyperplasia effect of MLB released on scaffold was analyzed for VSMCs and human umbilical vein endothelial cell (HUVEC) and method for selective inhibition from the difference of growth and migration of VSMCs and HUVECs was suggested.