Liao S, Curci J A, Kelley B J, Sicard G A, Thompson R W
Department of Surgery (Section of Vascular Surgery), Washington University School of Medicine, St. Louis, Missouri 63110, USA.
J Surg Res. 2000 Jul;92(1):85-95. doi: 10.1006/jsre.2000.5878.
Abdominal aortic aneurysms (AAAs) are associated with aging and atherosclerosis. AAAs arise through a degenerative process characterized in part by depletion of medial smooth muscle cells (SMC), suggesting that generalized aging and SMC senescence represent potential mechanisms contributing to aneurysmal degeneration. It is not yet known whether SMC from AAA tissue exhibit a difference in proliferative capacity compared to SMC from nonaneurysmal vessels or to what extent such differences might be due to aging alone or other patient-specific factors.
Aneurysm wall tissues were obtained from 15 patients undergoing AAA repair. In each case, a segment of the adjacent (nonaneurysmal) inferior mesenteric artery (IMA) from the same patient was used as a control. Paired AAA- and IMA-derived SMC strains were obtained by explant techniques and their proliferative capacities were compared during serial passage in culture.
Sustainable SMC cultures were established from all IMA explants but from only 9 of 15 AAAs (P < 0.05). The interval required to achieve primary explant growth was longer for AAAs than IMAs (16.4 +/- 2 vs 6.4 +/- 1 days; P < 0.001), but it was unrelated to patient age, gender, or aneurysm size. AAA-derived SMC appeared larger and rounder than the corresponding IMA-derived SMC, even after repeated passage in culture, and their maximal proliferation was reduced by 44.2 +/- 8% (n = 5 pairs, P < 0.05). Serum-stimulated [(3)H]thymidine uptake in AAA-derived SMC was also reduced by 54.9 +/- 7% (n = 5 pairs, P < 0.01), but flow cytometry revealed no differences in SMC viability, apoptosis, or necrosis. While IMA-derived SMC continued to proliferate beyond passage 20 during serial subculture, all AAA-derived SMC developed replicative senescence by passage 12.
AAA-derived SMC exhibit a distinct morphologic appearance in culture, a diminished proliferative capacity compared to SMC from the adjacent IMA, and a limited in vitro life span. These differences reflect an intrinsic alteration in SMC growth capacity independent of age alone. Tissue-specific processes leading to accelerated replicative senescence may therefore contribute to the selective medial SMC depletion observed in AAAs.
腹主动脉瘤（AAA）与衰老和动脉粥样硬化相关。AAA通过一种退行性过程形成，部分特征为中膜平滑肌细胞（SMC）减少，这表明全身衰老和SMC衰老可能是导致动脉瘤退变的潜在机制。目前尚不清楚与非动脉瘤血管来源的SMC相比，AAA组织来源的SMC在增殖能力上是否存在差异，以及这种差异在多大程度上仅由衰老或其他患者特异性因素引起。
从15例行AAA修复术的患者获取动脉瘤壁组织。在每种情况下，取自同一患者的相邻（非动脉瘤性）肠系膜下动脉（IMA）片段用作对照。通过组织块培养技术获得配对的AAA和IMA来源的SMC株，并在连续传代培养过程中比较它们的增殖能力。
所有IMA组织块均成功建立可持续的SMC培养物，但15个AAA组织中只有9个成功（P < 0.05）。AAA组织达到原代组织块生长所需的时间比IMA组织长（16.4 ± 2天对6.4 ± 1天；P < 0.001），但与患者年龄、性别或动脉瘤大小无关。即使在培养中反复传代后，AAA来源的SMC看起来比相应的IMA来源的SMC更大更圆，其最大增殖能力降低了44.2 ± 8%（n = 5对，P < 0.05）。血清刺激下AAA来源的SMC中[³H]胸苷摄取也降低了54.9 ± 7%（n = 5对，P < 0.01），但流式细胞术显示SMC活力、凋亡或坏死无差异。在连续传代培养过程中，IMA来源的SMC在第20代后仍继续增殖，而所有AAA来源的SMC在第12代时出现复制性衰老。
AAA来源的SMC在培养中呈现独特的形态外观，与相邻IMA来源的SMC相比增殖能力降低，体外寿命有限。这些差异反映了SMC生长能力的内在改变，不仅仅取决于年龄。因此，导致加速复制性衰老的组织特异性过程可能是AAA中观察到的中膜SMC选择性减少的原因。
