Wall shear stress and strain modulate experimental aneurysm cellularity
Wall shear stress and strain modulate experimental aneurysm cellularity
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DOI：
10.1016/s0741-5214(03)70052-4
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发表时间：
2003-05-01
影响因子：
4.3
通讯作者：
Dalman, RL
中科院分区：
文献类型：
--
作者：
Hoshina, K;Sho, E;Dalman, RL
目的：临床证据表明血流动力学状况影响腹主动脉瘤(AAA)疾病。我们对血流进行了修正，以评价壁面切应力(WSS)和相对壁面应变(RWS)对动脉瘤结构和细胞数量的影响。方法：用猪胰腺弹性酶建立啮齿动物AAA模型。组1的AAA WSS随左股动静脉瘘的形成而增加，而组2的AAA WSS随左髂动脉结扎而减少。记录两组患者的主动脉流量、室壁运动和血压。比较AAA直径、内皮细胞和平滑肌细胞(CD31和α-平滑肌肌动蛋白免疫染色)、细胞增殖标志物(5-溴脱氧尿苷)、内皮细胞和平滑肌细胞生长因子产生(血管内皮生长因子-D和血小板衍生生长因子-β)、细胞凋亡率(脱氧尿嘧啶核苷缺口末端标记[TUNEL]染色)等指标。动静脉瘘的建立使WSS(高流量AAA)增加300%，RWS增加150%。髂骨结扎使WSS(低流量AAA)减少60%。两种方法都没有显著改变收缩压、舒张压或平均主动脉压。在注射弹性酶7天后处死动物，低流量的AAA显著大于高流量的AAA。高流量的AAA还含有更多的内皮细胞和平滑肌细胞，并有证据表明生长因子的产生增加，细胞增殖，细胞凋亡减少。两组间AAA炎性细胞浸润的类型和严重程度无差异。结论：高血流状态刺激实验性动脉瘤内皮细胞和平滑肌细胞的增殖。细胞密度增加可以稳定主动脉的完整性，限制动脉瘤的生长。增加的下肢活动可能通过对内皮细胞和平滑肌细胞介导的主动脉重塑起到有益的作用，从而预防或延缓AAA疾病。
Objective: Clinical evidence indicates that hemodynamic conditions influence abdominal aortic aneurysm (AAA) disease. We modified blood flow to evaluate the effects of wall shear stress (WSS) and relative wall strain (RWS) on aneurysm structure and cellularity.Methods: Rodent AAAs were created with porcine pancreatic elastase infusion. In group 1 AAA WSS was increased with left femoral arteriovenous fistula creation, whereas in group 2 AAA WSS was decreased with left iliac artery ligation. Aortic flow, wall motion, and blood pressure were recorded in both groups. AAA diameter, endothelial and smooth muscle cellularity (CD31 and alpha-smooth muscle actin immunostaining), markers for cell proliferation (5-bromodeoxyuridine), endothelial and smooth muscle cell growth factor production (vascular endothelial growth factor-D and platelet-derived growth factor-beta, respectively), and apoptosis (deoxyuridine triphosphate nick end-labeled [TUNEL] stain) were compared between groups when the animals were killed.Results. Arteriovenous fistula creation increased WSS (high-flow AAA) by 300% and RWS by 150%. Iliac ligation reduced WSS (low-flow AAA) by 60%. Neither procedure significantly altered systolic, diastolic, or mean aortic pressure. When the animals were killed 7 days after elastase infusion, low-flow AAAs were significantly larger than high-flow AAAs. High-flow AAAs also contained more endothelial cells and smooth muscle cells, and evidence of increased growth factor production, cell proliferation, and decreased apoptosis. No difference in type or severity of AAA inflammatory cell infiltrate was noted between groups.Conclusions: High flow conditions stimulate endothelial cell and smooth muscle cell proliferation in experimental aneurysms. Enhanced cellularity may stabilize aortic integrity, limiting aneurysm growth. Increased lower extremity activity may prevent or retard AAA disease through salutary effects on aortic remodeling mediated by endothelial cells and smooth muscle cells.