压力与内皮细胞共培养通过直接和旁分泌机制上调肌细胞Fas-FasL途径并诱导细胞凋亡。

Pressure and endothelial coculture upregulate myocytic Fas-FasL pathway and induce apoptosis by way of direct and paracrine mechanisms.

作者信息

Vouyouka Agelikie G, Lin Lifeng, Basson Marc D

机构信息

Department of Surgery, John D. Dingell Veterans Administration Medical Center, 4646 John R St., Detroit MI 48201-1932, USA.

出版信息

Am J Surg. 2005 Nov;190(5):780-6. doi: 10.1016/j.amjsurg.2005.07.020.

DOI:10.1016/j.amjsurg.2005.07.020

PMID:16226958

Abstract

BACKGROUND

Pressurized endothelial cell (EC)-smooth muscle cell (SMCs) coculture significantly increases the apoptosis of SMCs. Our current hypothesis was that in EC-SMC coculture, pressure upregulates SMC apoptosis SMCs through EC-derived paracrine factors and that SMC apoptosis is induced through Fas-Fas ligand (FasL) activation.

METHODS

Conditioned media (CM) from ECs and SMCs exposed to ambient or high pressure was transferred to recipient SMCs. SMCs were stained with terminal deoxynucleotide transferase-mediated deoxy uridine triphosphate nick-end labeling. Fas and FasL expression was assessed in SMC grown in monoculture, coculture with EC, pressurized monoculture, and pressurized coculture with EC.

RESULTS

CM from pressurized ECs caused a 30% increase in SMC apoptosis compared with CM from control ECs (P < .05). Pressure increased Fas and FasL expression in monocultured and cocultured SMCs (1.6-fold and 2.3-fold for Fas [P < .05] and 1.65-fold and 1.7-fold for FasL [P < or = .05]). Coculture had synergistic effect on Fas expression and no effect on FasL expression.

CONCLUSIONS

Pressure plays significant role in EC-SMC interaction, SMC apoptosis, and vascular remodeling.

摘要

背景

内皮细胞（EC）-平滑肌细胞（SMC）共培养体系中施加压力可显著增加SMC的凋亡。我们目前的假说是，在EC-SMC共培养体系中，压力通过EC分泌的旁分泌因子上调SMC凋亡，且SMC凋亡是通过Fas-Fas配体（FasL）激活诱导产生的。

方法

将暴露于常压或高压环境下的EC和SMC的条件培养基（CM）转移至受体SMC。用末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸缺口末端标记法对SMC进行染色。评估在单纯培养、与EC共培养、加压单纯培养以及与EC加压共培养条件下生长的SMC中Fas和FasL的表达情况。

结果

与对照EC的CM相比，加压EC的CM使SMC凋亡增加了30%（P < .05）。压力使单纯培养和共培养的SMC中Fas和FasL的表达增加（Fas分别增加1.6倍和2.3倍[P < .05]，FasL分别增加1.65倍和1.7倍[P ≤ .05]）。共培养对Fas表达有协同作用，对FasL表达无影响。