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The clinical correlation of race with iliac vein stenting
Vol. 221, No. 4S2, October 2015
models. We developed a decellularization protocol that removed cellular components from normal pig kidneys and the decellularized kidney scaffold maintained vascular patency after implantation (less than 2 h) in vivo. To address the limitation of short term assessment, this study aims to optimize decellularization methods that can preserve functional vascular architecture for long-term implantation. METHODS: We compared three different decellularization protocols (1% Triton X-100, 0.25% and 0.5% SDS) and assessed the effects of the decellularization on the maintenance of pig kidney’s glomeruli and afferent artery using angiography, vascular corrosion casts, and scanning electron microscopy (SEM) analysis. A vascular casting technique was used to analyze normal vascular morphology and functional architecture. RESULTS: Angiographic images of native and decellularized kidneys using three decellularization methods show clear visualization of main renal artery, segmental and lobar arteries, indicating no structural changes after decellularization. SEM analysis of the vascular casts of the different kidneys demonstrate that native 1% Triton treated kidney retained small arteries and glomeruli structures compared with the decellularized kidneys with SDS treatment. CONCLUSIONS: Results demonstrated that the decellularization protocol using 1% Triton X-100 was most effective in preserving microvasculature and that the optimized method can contribute to vascular patency long-term following kidney implantation. TGF-b/Smad3 stimulates CD34 expression, MAPK activation and vascular smooth muscle cell proliferation Xudong Shi, MD, PhD, Katie Wang, Liang-Wang Guo, PhD, Bowen Wang, Mengxue Zhang, MD, Mirnal A Chaudhary, MD, Sarah Franco, Yichen Zhu, K Craig Kent, MD, FACS University of Wisconsin-Madison, Madison, WI INTRODUCTION: Our previous studies show that TGF-b/Smad3 signaling plays an important role in the phenotypic switching of vascular smooth muscle cells (SMCs) from a quiescent to a proliferative state and promotes intimal hyperplasia; TGF-b/Smad3 also regulate stem cell and developmental related genes (such as CD34). In this study, we tested the hypothesis that TGF-b/Smad3 stimulates CD34 expression, MAPK activation and SMC proliferation. METHODS: Microarray, RT-PCR, Western blotting. RESULTS: Microarray analysis showed that w300 genes are altered by TGF-b/Smad3 treatment in vascular SMC. Amongst these genes, CD34 stands out in particular due to its greater than 30-fold upregulation and its reported functions as a progenitor cell marker that regulates cell migration and proliferation. An increase of CD34 mRNA (425.6 fold, n¼3, p<0.05) and protein expression (2.80.35 fold, n¼3, p<0.05) after TGF-b/ Smad3 treatment was confirmed by quantitative RT-PCR and Western blotting, respectively. We generated a panel of Smad3 mutants in which point mutations were introduced to the ‘hot spots’
Scientific Forum: 2015 Clinical Congress
e43
responsible for key protein-protein interactions. Our data showed that mutations that inhibited Smad3’s ability to upregulate CD34 expression and MAPK activation also disrupted its ability to stimulate SMC proliferation. Conversely, the Smad3 mutants that showed greater effects on CD34 expression and MAPK activation produced higher ability to stimulate SMC proliferation. CONCLUSIONS: Our data suggest that CD34 is an important downstream target of TGF-/Smad3 and may play a role in the phenotypic switch of SMCs. Identification of the mutations responsible for TGF-b stimulated CD34 expression, MAPK activation and SMC proliferation might provide novel targets for the pharmacological blockade of intimal hyperplasia. The clinical correlation of race with iliac vein stenting Ahmad A Alsheekh, MD, Anil P Hingorani, MD, FACS, Enrico Ascher, MD, FACS, Natalie Marks, MD, Samson Ferm, Pavel Kibrik Total Vascular Care, Brooklyn, NY INTRODUCTION: There have been well documented implications of race on the outcome of various vascular diseases. Little literature has examined the effect of race on venous disease. Iliac vein stenting is an emerging technology in treating chronic venous insufficiency (CVI). To further characterize this disease and its treatment, we chose to study the effect of race on iliac vein stenosis and its treatment with iliac vein stenting. METHODS: In this observational study, data analysis was performed for 623 patients with CVI who underwent iliac vein stenting during the time period from August 2012 to September 2014. Patients were categorized as Caucasian (n¼396), Black (n¼89) or Hispanic (n¼138) and other (n¼23). These were correlated with the age, gender, percentage of iliac vein stenosis, postoperative thrombosis, CEAP classification and pain score. Pain score was obtained post-operative on a scale of 1-10. Follow up was performed after completion of the procedure, through postoperative visits and duplex exams every 3 months. Statistical analysis performed using Chi-square and Student’s T-test. RESULTS: Average age of the study patients was 67.8 years (age range 23-96 years and SD14.2). 67% of patients were females. Average CEAP score was 3.6 (SD1.2). The average pain score was 2.6 (SD2.9). Average degree of stenosis was 64.9% (SD13.8). The number of patient with iliac vein stent thrombosis was 14 patients (0.02%). When analyzing each race, we found Caucasians were significantly older than Blacks and Hispanics (p<0.0001). There tended to be more females in the Caucasian group as compared to the Hispanics (p¼0.04). Hispanics tended to have higher pain scores post-operatively than Whites (p¼0.01). There were no differences in CEAP classification, degree of stenosis and postoperative iliac vein stent thrombosis between the three groups. CONCLUSIONS: These data do suggest significant differences in post-operative pain between different races. These differences suggest that selective treatment strategies may be warranted by race.
models. We developed a decellularization protocol that removed cellular components from normal pig kidneys and the decellularized kidney scaffold maintained vascular patency after implantation (less than 2 h) in vivo. To address the limitation of short term assessment, this study aims to optimize decellularization methods that can preserve functional vascular architecture for long-term implantation. METHODS: We compared three different decellularization protocols (1% Triton X-100, 0.25% and 0.5% SDS) and assessed the effects of the decellularization on the maintenance of pig kidney’s glomeruli and afferent artery using angiography, vascular corrosion casts, and scanning electron microscopy (SEM) analysis. A vascular casting technique was used to analyze normal vascular morphology and functional architecture. RESULTS: Angiographic images of native and decellularized kidneys using three decellularization methods show clear visualization of main renal artery, segmental and lobar arteries, indicating no structural changes after decellularization. SEM analysis of the vascular casts of the different kidneys demonstrate that native 1% Triton treated kidney retained small arteries and glomeruli structures compared with the decellularized kidneys with SDS treatment. CONCLUSIONS: Results demonstrated that the decellularization protocol using 1% Triton X-100 was most effective in preserving microvasculature and that the optimized method can contribute to vascular patency long-term following kidney implantation. TGF-b/Smad3 stimulates CD34 expression, MAPK activation and vascular smooth muscle cell proliferation Xudong Shi, MD, PhD, Katie Wang, Liang-Wang Guo, PhD, Bowen Wang, Mengxue Zhang, MD, Mirnal A Chaudhary, MD, Sarah Franco, Yichen Zhu, K Craig Kent, MD, FACS University of Wisconsin-Madison, Madison, WI INTRODUCTION: Our previous studies show that TGF-b/Smad3 signaling plays an important role in the phenotypic switching of vascular smooth muscle cells (SMCs) from a quiescent to a proliferative state and promotes intimal hyperplasia; TGF-b/Smad3 also regulate stem cell and developmental related genes (such as CD34). In this study, we tested the hypothesis that TGF-b/Smad3 stimulates CD34 expression, MAPK activation and SMC proliferation. METHODS: Microarray, RT-PCR, Western blotting. RESULTS: Microarray analysis showed that w300 genes are altered by TGF-b/Smad3 treatment in vascular SMC. Amongst these genes, CD34 stands out in particular due to its greater than 30-fold upregulation and its reported functions as a progenitor cell marker that regulates cell migration and proliferation. An increase of CD34 mRNA (425.6 fold, n¼3, p<0.05) and protein expression (2.80.35 fold, n¼3, p<0.05) after TGF-b/ Smad3 treatment was confirmed by quantitative RT-PCR and Western blotting, respectively. We generated a panel of Smad3 mutants in which point mutations were introduced to the ‘hot spots’
Scientific Forum: 2015 Clinical Congress
e43
responsible for key protein-protein interactions. Our data showed that mutations that inhibited Smad3’s ability to upregulate CD34 expression and MAPK activation also disrupted its ability to stimulate SMC proliferation. Conversely, the Smad3 mutants that showed greater effects on CD34 expression and MAPK activation produced higher ability to stimulate SMC proliferation. CONCLUSIONS: Our data suggest that CD34 is an important downstream target of TGF-/Smad3 and may play a role in the phenotypic switch of SMCs. Identification of the mutations responsible for TGF-b stimulated CD34 expression, MAPK activation and SMC proliferation might provide novel targets for the pharmacological blockade of intimal hyperplasia. The clinical correlation of race with iliac vein stenting Ahmad A Alsheekh, MD, Anil P Hingorani, MD, FACS, Enrico Ascher, MD, FACS, Natalie Marks, MD, Samson Ferm, Pavel Kibrik Total Vascular Care, Brooklyn, NY INTRODUCTION: There have been well documented implications of race on the outcome of various vascular diseases. Little literature has examined the effect of race on venous disease. Iliac vein stenting is an emerging technology in treating chronic venous insufficiency (CVI). To further characterize this disease and its treatment, we chose to study the effect of race on iliac vein stenosis and its treatment with iliac vein stenting. METHODS: In this observational study, data analysis was performed for 623 patients with CVI who underwent iliac vein stenting during the time period from August 2012 to September 2014. Patients were categorized as Caucasian (n¼396), Black (n¼89) or Hispanic (n¼138) and other (n¼23). These were correlated with the age, gender, percentage of iliac vein stenosis, postoperative thrombosis, CEAP classification and pain score. Pain score was obtained post-operative on a scale of 1-10. Follow up was performed after completion of the procedure, through postoperative visits and duplex exams every 3 months. Statistical analysis performed using Chi-square and Student’s T-test. RESULTS: Average age of the study patients was 67.8 years (age range 23-96 years and SD14.2). 67% of patients were females. Average CEAP score was 3.6 (SD1.2). The average pain score was 2.6 (SD2.9). Average degree of stenosis was 64.9% (SD13.8). The number of patient with iliac vein stent thrombosis was 14 patients (0.02%). When analyzing each race, we found Caucasians were significantly older than Blacks and Hispanics (p<0.0001). There tended to be more females in the Caucasian group as compared to the Hispanics (p¼0.04). Hispanics tended to have higher pain scores post-operatively than Whites (p¼0.01). There were no differences in CEAP classification, degree of stenosis and postoperative iliac vein stent thrombosis between the three groups. CONCLUSIONS: These data do suggest significant differences in post-operative pain between different races. These differences suggest that selective treatment strategies may be warranted by race.