Adili F, Statius van Eps R G, Karp S J, Watkins M T, LaMuraglia G M
Division of Vascular Surgery, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA.
J Vasc Surg. 1996 Apr;23(4):698-705. doi: 10.1016/s0741-5214(96)80052-8.
Photodynamic therapy (PDT) has been demonstrated to inhibit experimental intimal hyperplasia and to lead to expedient reendothelialization but negligible repopulation of the vessel media. The mechanism that underlies the differential ingrowth of cells into PDT-treated vessel segments is not understood. Because the extracellular matrix (ECM) is known to modulate specific cell functions, this study was designed to determine whether PDT of isolated ECM affects the function of endothelial cells (ECs) and smooth muscle cells (SMCs).
PDT of bovine aortic EC-ECM was performed with chloroaluminum sulfonated phthalocyanine and 675-nm laser light. Control specimens included untreated ECM, ECM-free plates, and ECM exposed to either light or photosensitizer only. Cell function was characterized by attachment, proliferation, and migration of ECs or SMCs that were plated onto identically treated matrixes.
SMC attachment (86% +/- 0.4% vs 95% +/- 0.4%), proliferation (46% +/- 0.5% vs 100% +/- 1.4%), and migration (40% +/- 1.0% vs 100% +/- 0.9%) were significantly inhibited after PDT of ECM when compared with untreated ECM (all p < 0.001). In contrast, PDT of ECM significantly enhanced EC proliferation (129% +/- 6.2% vs 100% +/- 6.2%; p < 0.03) and migration (118% +/- 2% vs 100% +/- 0.8; p < 0.01), but did not affect attachment.
This report establishes PDT-induced changes in the ECM with a result of inhibition of SMCs and stimulation of EC functions. It provides insight into how PDT-treated arteries can develop favorable EC repopulation without SMC-derived intimal hyperplasia. These findings may help provide a better understanding of the interactions between cells and their immediate environment in vascular remodeling.
光动力疗法(PDT)已被证明可抑制实验性内膜增生并促进快速再内皮化,但血管中膜的细胞再填充可忽略不计。细胞向经PDT处理的血管段内生长差异的潜在机制尚不清楚。由于已知细胞外基质(ECM)可调节特定细胞功能,本研究旨在确定分离的ECM的PDT是否会影响内皮细胞(ECs)和平滑肌细胞(SMCs)的功能。
用磺化铝酞菁和675纳米激光对牛主动脉EC-ECM进行PDT。对照标本包括未处理的ECM、无ECM的平板以及仅暴露于光或光敏剂的ECM。通过接种到相同处理基质上的ECs或SMCs的附着、增殖和迁移来表征细胞功能。
与未处理的ECM相比,ECM的PDT后,SMCs的附着(86%±0.4%对95%±0.4%)、增殖(46%±0.5%对100%±1.4%)和迁移(40%±1.0%对100%±0.9%)均受到显著抑制(所有p<0.001)。相比之下,ECM的PDT显著增强了EC的增殖(129%±6.2%对100%±6.2%;p<0.03)和迁移(118%±2%对100%±0.8;p<0.01),但不影响附着。
本报告证实了PDT诱导的ECM变化,结果是抑制SMCs并刺激EC功能。它有助于深入了解经PDT处理的动脉如何在无SMC衍生的内膜增生情况下实现有利的EC再填充。这些发现可能有助于更好地理解血管重塑过程中细胞与其直接环境之间的相互作用。