Chuanqi Cai1, Binxia Yang2, Sreenivasulu Kilari2, Yiqing Li3, Chenglei Zhao4, Amit Sharma2, Sanjay Misra5. 1. Department of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China; Vascular and Interventional Radiology Translational Laboratory, Department of Radiology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905. 2. Vascular and Interventional Radiology Translational Laboratory, Department of Radiology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905. 3. Department of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. 4. Vascular and Interventional Radiology Translational Laboratory, Department of Radiology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905; Department of Vascular Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China. 5. Vascular and Interventional Radiology Translational Laboratory, Department of Radiology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905; Department of Biochemistry and Molecular Biology Mayo Clinic, Rochester, Minnesota; Department of Radiology, Vascular and Interventional Radiology, Mayo Clinic, 200 First St SW, Rochester, Minnesota, 55905. Electronic address: misra.sanjay@mayo.edu.
Abstract
PURPOSE: To develop a clinically relevant model of percutaneous transluminal angioplasty (PTA) of venous stenosis in mice with arteriovenous fistula (AVF); to test the hypothesis that there is increased wall shear stress (WSS) after PTA; and to histologically characterize the vessels. MATERIALS AND METHODS: Thirteen C57BL/6J male mice, 6-8 weeks old, underwent partial nephrectomy to create chronic kidney disease. Twenty-eight days later, an AVF was created from the right external jugular vein to the left carotid artery. Fourteen days later, an angioplasty or sham procedure was performed, and the mice were sacrificed 14 days later for histologic evaluation to identify the cells contributing to the vascular remodeling (α-SMA, FSP-1, CD31, and CD68), proliferation (Ki-67), cell death (TUNEL), and hypoxia staining (HIF-1α). Histomorphometric analysis was performed to assess lumen area, neointima+media area, and cellular density. Ultrasound was performed weekly after creation of the AVF. RESULTS: Venous stenosis occurred 14 days after the creation of an AVF. PTA-treated vessels had significantly higher WSS; average peak systolic velocity, with increased lumen vessel area; and decreased neointima + media area compared to sham controls. There was a significant decrease in the staining of smooth muscle cells, fibroblasts, macrophages, HIF-1α, proliferation, and apoptosis and an increase in CD31-(+) cells. CONCLUSIONS: A clinically relevant model of PTA of venous stenosis in mice was created. PTA-treated vessels had increased lumen vessel area and WSS. The alterations in tissue markers of vascular remodeling, tissue hypoxia, proliferation, and cell death may be implications for future design of drug and device development.
PURPOSE: To develop a clinically relevant model of percutaneous transluminal angioplasty (PTA) of venous stenosis in mice with arteriovenous fistula (AVF); to test the hypothesis that there is increased wall shear stress (WSS) after PTA; and to histologically characterize the vessels. MATERIALS AND METHODS: Thirteen C57BL/6J male mice, 6-8 weeks old, underwent partial nephrectomy to create chronic kidney disease. Twenty-eight days later, an AVF was created from the right external jugular vein to the left carotid artery. Fourteen days later, an angioplasty or sham procedure was performed, and the mice were sacrificed 14 days later for histologic evaluation to identify the cells contributing to the vascular remodeling (α-SMA, FSP-1, CD31, and CD68), proliferation (Ki-67), cell death (TUNEL), and hypoxia staining (HIF-1α). Histomorphometric analysis was performed to assess lumen area, neointima+media area, and cellular density. Ultrasound was performed weekly after creation of the AVF. RESULTS: Venous stenosis occurred 14 days after the creation of an AVF. PTA-treated vessels had significantly higher WSS; average peak systolic velocity, with increased lumen vessel area; and decreased neointima + media area compared to sham controls. There was a significant decrease in the staining of smooth muscle cells, fibroblasts, macrophages, HIF-1α, proliferation, and apoptosis and an increase in CD31-(+) cells. CONCLUSIONS: A clinically relevant model of PTA of venous stenosis in mice was created. PTA-treated vessels had increased lumen vessel area and WSS. The alterations in tissue markers of vascular remodeling, tissue hypoxia, proliferation, and cell death may be implications for future design of drug and device development.
Authors: Sanjay Misra; David A Woodrum; Jay Homburger; Stephane Elkouri; Jayawant N Mandrekar; Victor Barocas; James F Glockner; Dheeraj K Rajan; Debabrata Mukhopadhyay Journal: Cardiovasc Intervent Radiol Date: 2006 Jul-Aug Impact factor: 2.740
Authors: Sanjay Misra; Alex A Fu; Alessandra Puggioni; James F Glockner; Dheeraj K Rajan; Michael A McKusick; Haraldur Bjarnason; Debabrata Mukhopadhyay Journal: J Vasc Interv Radiol Date: 2008-02 Impact factor: 3.464
Authors: Sanjay Misra; Alex A Fu; Alessandra Puggioni; Kamran M Karimi; Jaywant N Mandrekar; James F Glockner; Luis A Juncos; Bilal Anwer; Antonio M McGuire; Debabrata Mukhopadhyay Journal: Am J Physiol Heart Circ Physiol Date: 2008-03-07 Impact factor: 4.733
Authors: Anton N Sidawy; Lawrence M Spergel; Anatole Besarab; Michael Allon; William C Jennings; Frank T Padberg; M Hassan Murad; Victor M Montori; Ann M O'Hare; Keith D Calligaro; Robyn A Macsata; Alan B Lumsden; Enrico Ascher Journal: J Vasc Surg Date: 2008-11 Impact factor: 4.268
Authors: Chenglei Zhao; Sean T Zuckerman; Chuanqi Cai; Sreenivasulu Kilari; Avishek Singh; Michael Simeon; Horst A von Recum; Julius N Korley; Sanjay Misra Journal: J Am Heart Assoc Date: 2020-12-05 Impact factor: 5.501