波浪狀型態調控血管平滑肌細胞之肌動蛋白結構與表現型

Abstract

彈性動脈組織內富含捲曲的細胞外間質纖維束，這些纖維束會控制組織的力學性質，組織中的血管平滑肌細胞也會沿著波浪狀纖維生長，並調節組織的恆定。隨著人體的老化、疾病以及損傷，此類細胞外間質結構會受到破壞，並伴隨著血管平滑肌細的表現型的轉變。本研究發展微溝槽系統來模仿健康的組織結構，並假設彎曲結構可以調控血管平滑肌細胞表現型。在波浪狀結構中，細胞擁有較高的收縮蛋白表現量與較低的細胞生長率，顯示出血管平滑肌細胞的表現型轉變；同時，波浪狀細胞具有似偽足結構，並藉由肌動蛋白的收縮力使細胞核形變，藉此抑制細胞增生並改變染色質結構。本研究提供了調控血管平滑肌細胞表現型與治療心血管疾病潛在目標的新觀點。

Elastic arteries are rich in tortuous ECM bundles that contribute to tissue mechanics. Vascular smooth muscle cells (VSMCs) reside in the wavy structure, follow the wavy morphology, and regulate tissue homeostasis. During aging, disease, and injury, the ECM structure deteriorates, which is accompanied by phenotypic switch of VSMCs. In this study, we developed a microgroove system to mimic the wavy structures in healthy tissues and hypothesized that waviness regulates VSMC phenotype. Enhanced contractile apparatus expression and suppressed proliferation in the wavy cells suggested the improvement of contractile VSMC phenotype. We also described the lamellipodia-like structures in the wavy cells. The structures were found to negatively regulate proliferation and change chromatin organization by compressing and deforming the nuclei via actin contractility. Our study provides new insights in the regulation of VSMC phenotype and potential target for treatment of cardiovascular diseases.