Objective To investigate the effect of lumbar sympathectomy on collateral vessel formation and angiogenesis in a rat model of hindlimb ischemia. Methods A femoral artery ligation-induced hindlimb ischemia model was established in Sprague-Dawley rats, which were randomly divided into a control group and a sympathectomy group. The latter underwent bilateral lumbar sympathectomy. On postoperative day 14, collateral vessel formation in the ischemic limb was assessed by X-ray angiography and Micro-CT three-dimensional reconstruction, and vessel diameters were measured. Immunofluorescence double staining with α-SMA and CD31 was performed to visualize vascular structures, and Ki67 staining was used to evaluate the proliferative activity of vascular smooth muscle cells, thereby comprehensively analyzing vascular repair and regeneration. Blood perfusion in the plantar region was assessed on postoperative days 3, 7, and 14 using laser speckle imaging. On day 30, hematoxylin and eosin (H&E) staining was used to measure gastrocnemius fiber cross-sectional area, count CD31-positive microvessels, and detect VEGFA protein expression (day 3). On day 7, flow cytometry was performed to analyze the polarization ratio of M1/M2 macrophages in the adductor muscle group. Results Compared with the control group, the sympathectomy group exhibited a significantly larger mean collateral vessel diameter (0.52±0.09 mm vs. 0.38±0.07 mm, P<0.01) and increased numbers of α-SMA⁺/Ki67⁺ cells (5.38±0.87 vs. 2.22±0.64, P<0.01). Blood perfusion recovery rates on postoperative days 3, 7, and 14 were significantly improved (P<0.05). By day 30, gastrocnemius fiber cross-sectional area was markedly enlarged (1706±92 μm² vs. 1145±132 μm², P<0.001), CD31-positive microvessel counts were increased (171±19 vs. 93±8, P<0.001), and VEGFA expression was significantly upregulated (P<0.01). Moreover, the proportion of M2 macrophages was significantly elevated (28.7±3.0% vs. 17.8±2.2%, P<0.01), while the proportion of M1 macrophages showed no significant difference. Conclusions Lumbar sympathectomy effectively promotes collateral vessel growth and angiogenesis in ischemic rat hindlimbs. The underlying mechanism may involve the induction of macrophage polarization toward the M2 phenotype and upregulation of VEGFA expression.
Key words
Lumbar sympathectomy /
  /
  /
Hindlimb ischemia /
  /
  /
Collateral vessel growth /
  /
  /
Angiogenesis /
  /
  /
Macrophage polarization
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
References
[1] Shu J, Santulli G. Update on peripheral artery diseas: Epidemiology and evidence-based facts[J]. Atherosclerosis, 2018, 275: 379-381. DOI:10.1016/j.atherosclerosis.2018.05.033.
[2] Conte MS, Bradbury AW, Kolh P, et al. Global vascular guidelines on the management of chronic limb-threatening ischemia[J]. Eur J Vasc Endovasc Surg, 2019, 58(1S): S1-S109.e33. DOI:10.1016/j.jvs.2019. 05.006.
[3] Kobayashi N, Hirano K, Nakano M, et al. Non-atherosclerotic peripheral artery disease: thromboangiitis obliterans and others[J]. Curr Opin Cardiol, 2020,35(6): 643-649. DOI:10.1097/HCO.00000000000 00783.
[4] He H, Liu X, Peng Y, et al. Stem cell therapy for lower extremity artery disease: a meta-analysis of randomized controlled trials[J]. Stem Cell Res Ther, 2020, 11(1): 1-13. DOI:10.1186/s13287-020-01936-4.
[5] Wang Y, Jin Y, Wang H, et al. Effect of lumbar sympathectomy on endovascular treatment outcomes in patients with lower limb ischemia[J]. Int Angiol, 2021, 40(2): 121-128. DOI:10.23736/S0392-9590.21. 04514-1.
[6] Ding H, Zhang Y, Liu Z, et al. Evaluation of the efficacy and safety of percutaneous chemical lumbar sympathectomy for lower limb ischemia: a retrospective study[J]. BMC Cardiovasc Disord, 2022, 22(1): 117. DOI:10.1186/s12872-022-02547-6.
[7] Ziegler KA, Engelhardt S, Carnevale D, et al. Neural mechanisms in cardiovascular health and disease[J]. Circ Res, 2025, 136(11): 1233-1261. DOI:10.1161/CIRCRESAHA.125.325580.
[8] Silva A, Hatch CJ, Chu MT, et al. Collateral arteriogenesis involves a sympathetic denervation that is associated with abnormal α-adrenergic signaling and a transient loss of vascular tone[J]. Front Cardiovasc Med, 2022, 9: 805810. DOI:10.3389/fcvm.2022.805810.
[9] Steinle J, Lashbrook B. Cervical sympathectomy regulates expression of key angiogenic factors in the rat choroid[J].Exp Eye Res, 2006 ,83(1):16-23. DOI: 10.1016/j.exer.2005.11.006.
[10]Luo M, Zhao F, Cheng H, et al. Macrophage polarization: an important role in inflammatory diseases[J]. Front Immunol, 2024, 15: 1352946. DOI:10.3389/fimmu.2024.1352946.
[11]Chen S, Saeed AFUH, Liu Q, et al. Macrophages in immunoregulation and therapeutics[J]. Signal Transduct Target Ther, 2023, 8: 207. DOI:10.1038/s41392-023-01452-1.
[12]Liu SY, Zhang B, Zhou JQ, et al. Inhibition of differentiation of monocyte-derived macrophages toward an M2-Like phenotype May Be a neglected mechanism of β-AR receptor blocker therapy for atherosclerosis[J]. Front Pharmacol, 2024, 5:15:1378787. DOI: 10.3389/fphar.2024.1378787.