Lipoplex gene transfer of inducible nitric oxide synthase inhibits the reactive intimal hyperplasia after expanded polytetrafluoroethylene bypass grafting

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Presentation transcript:

Lipoplex gene transfer of inducible nitric oxide synthase inhibits the reactive intimal hyperplasia after expanded polytetrafluoroethylene bypass grafting Tomas Pfeiffer, MD, PhD, Martina Wallich, PhD, Wilhelm Sandmann, MD, Jürgen Schrader, MD, PhD, Axel Gödecke, MD, PhD Journal of Vascular Surgery Volume 43, Issue 5, Pages 1021-1027 (May 2006) DOI: 10.1016/j.jvs.2006.01.014 Copyright © 2006 The Society for Vascular Surgery Terms and Conditions

Fig 1 Infiltrator catheter for intramural administration of lipoplex solution into the arterial vessel wall. The balloon, with a diameter of 4 mm, provides three bars (length, 15 mm) in an angle of 120° with seven microinjection ports each. Journal of Vascular Surgery 2006 43, 1021-1027DOI: (10.1016/j.jvs.2006.01.014) Copyright © 2006 The Society for Vascular Surgery Terms and Conditions

Fig 2 Immunohistochemical detection of inducible nitric oxide synthase (iNOS) expression in cells of arterial sections 3 days after pSCMV-iNOS and pSCMV2 (control vector) transfection. Note the intense staining of iNOS expression vessel segments (left). Journal of Vascular Surgery 2006 43, 1021-1027DOI: (10.1016/j.jvs.2006.01.014) Copyright © 2006 The Society for Vascular Surgery Terms and Conditions

Fig 3 Effect of inducible nitric oxide synthase (iNOS) gene transfer on smooth muscle cell proliferation 3 days after transfection with the pSCMV-iNOS vector (top left) or the control vector pSCMV2 (top right). Tissue slices were stained for nuclear Ki-67 accumulation as an indicator of cell-cycle progression. Ki-67–positive cells are stained brown (an example is circled); Ki-67–negative nuclei appear blue. Quantitative results of Ki-67–positive cells in control vector–transfected (n = 4) and pSCMV-iNOS–transfected (n = 4) vessels are shown (bottom). In comparison, the value of an untreated vessel is shown. Journal of Vascular Surgery 2006 43, 1021-1027DOI: (10.1016/j.jvs.2006.01.014) Copyright © 2006 The Society for Vascular Surgery Terms and Conditions

Fig 4 Polytetrafluoroethylene bypass grafts were inserted into the carotid artery of both sides in 10 foxhound dogs. The anastomotic region was transfected with pSCMV-iNOS lipoplexes on one side and with lipoplexes of a pSCMV2 control vector on the contralateral side. After 6 months, the prostheses were excised. In 50 cross sections of each anastomosis, the intimal thickness over the arterial vessel wall, the suture region, and the prosthetic wall was measured planimetrically. Means and standard deviations of 10 proximal and 10 distal anastomoses are given. The thickness of the neointima after inducible nitric oxide synthase (iNOS) transfection was significantly reduced (Wilcoxon test; P < .05). Journal of Vascular Surgery 2006 43, 1021-1027DOI: (10.1016/j.jvs.2006.01.014) Copyright © 2006 The Society for Vascular Surgery Terms and Conditions

Fig 5 Typical histologic finding of a bypass anastomosis after transfection of the arterial vessel wall with inducible nitric oxide synthase (iNOS; left) or a control vector (right). Asymmetric formation of neointima (N) of the control and inhibition of intimal hyperplasia after iNOS transfection are shown, as are corresponding cross sections of proximal anastomoses of the same animal. A, Arterial wall; P, polytetrafluoroethylene prosthesis (stain, orcein; original magnification, ×10). Journal of Vascular Surgery 2006 43, 1021-1027DOI: (10.1016/j.jvs.2006.01.014) Copyright © 2006 The Society for Vascular Surgery Terms and Conditions