- Email: [email protected]
Increased estrogen receptor alpha expression in experimental aortic aneurysms in females compared with males
S144
Surgical Forum Abstracts
J Am Coll Surg
⫹/⫺ 0.17 MPa), using an equivalence threshold (difference) of 0.24 MPa (p ⫽ .01). While peak wall stress and maximal diameter were correlated for FAs (r ⫽ .90), the correlation for SAs was less robust (r ⫽ .58).
These data provide mechanistic insight into this potentially devastating complication and suggest a potential therapeutic target.
CONCLUSIONS: Although the SAs were smaller than the FAs, mean peak wall stress was equivalent. In addition, maximum diameter and wall stress were more strongly correlated in FAs. Therefore, factors other than maximum diameter, such as aneurysm shape, may result in small SAs having a rupture risk equivalent to larger FAs. These results provide a rationale for the repair of small saccular descending thoracic aortic aneurysms.
Increased estrogen receptor alpha expression in experimental aortic aneurysms in females compared with males
Paralysis following thoracic aortic stenting is associated with endothelial nitric oxide synthase phosphorylation and nitric oxide production
INTRODUCTION: Estrogen receptor alpha (ERalpha) has been identified in the vessel wall, offering vasoprotective effects when upregulated. Estrogens are known to mediate the inflammatory mileu, and inflammation has long been associated with abdominal aortic aneurysm (AAA) formation. It has therefore been theorized that increased estrogen receptor in females contributes to their relative resistance to AAAs. This study’s objective was to determine gender differences in ERalpha levels during experimental AAA formation.
Christopher A Durham MD, Steven C Agle MD, Michael M McNally MD, Ashley C Mays BS, Abdel A Abdel-Rahman PhD, Michael C Stoner MD, FACS East Carolina University, Greenville, NC INTRODUCTION: Paralysis from spinal cord blood supply interruption after endovascular thoracic aortic repair remains a significant risk. The purpose of this study was to investigate the molecular basis of injury. METHODS: A rabbit model of thoracic endovascular repair was created as follows: animals were treated with aortography alone (control, n⫽7) or covered thoracic aortic stent (n⫽8). Each animal was scored three hours postoperatively by the Tarlov scale from 0 (no movement) to 5 (normal hop). Animals were then euthanized at either 1 or 3 hours postoperatively. In a subset of animals intracellular nitric oxide (NO) and superoxide production in thoracic spinal cord sections were investigated with 4-amino-5-methylamino-2⬘,7⬘dilfuorofluorescein (DAF) and dihydroethidium (DHE). A Western blot analysis was performed on both 1 and 3 hour control and stented tissue, and a phosphorylated endothelial nitric oxide synthase (eNOS): eNOS index was determined. RESULTS: Paralysis scores of stented animals were significantly lower than control animals at three hours postoperatively, indicative of severe neurological injury. In the rabbits euthanized at three hours, intracellular nitric oxide production was significantly increased in stented animals. Superoxide production was present in the stented animals; however this did not reach significance. Analysis of the Western blot revealed stented animals had a higher phosphorylated eNOS: eNOS index than controls at both time points (Table, * p⬍0.05, ** p⬍0.01). p-eNOS : eNOS 1° Aortography
30% ⫾ 1%
DHE
Tarlov Score
43.7 ⫾ 4.6
DAF
12.6 ⫾ 2.8
N/A
1° Stent
39% ⫾ 2%**
44.3 ⫾ 4.4
14.6 ⫾ 5.3
N/A
3° Aortography
30% ⫾ 1%
43.9 ⫾ 4.0
13.3 ⫾ 7.9
4.0 ⫾ 0.0
3° Stent
36% ⫾ 2%*
63.0 ⫾ 4.8**
24.7 ⫾ 3.3
1.34 ⫾ 0.8**
CONCLUSIONS: Thoracic aortic stenting is associated with neurological injury, increased phosphorylated eNOS, and NO production.
Adriana Laser MD, MPH, Abhijit Ghosh PhD, Karen J Roelofs DVM, Paul Dimusto MD, Omar Sadiq, Brendan McEvoy BA, Kristopher Barrett Deatrick MD, Jonathan L Eliason MD, Peter K Henke MD, FACS, Gilbert R Upchurch Jr MD, FACS University of Michigan, Ann Arbor, MI
METHODS: Infrarenal aortas of male and female C57 mice (n⫽18 and n⫽16, respectively) were infused with 0.4% elastase. Diameters were measured at day 0 and postoperative day 14. Aortic mRNA expression of ERalpha was determined on day 3 by RTPCR, while ERalpha protein levels were measured via Western blot. Immunohistochemistry using a rabbit antibody for ERalpha was performed on day 14 samples and quantified. Data were compared for significance using a student t-test. RESULTS: Infrarenal aortic diameter increased in elastase-perfused males (ME) by 80% at 14 days post perfusion, while females (FE) increased by only 35% (p⫽0.0012). Paradoxically, FE had 10x greater ERalpha mRNA expression compared with ME (p⫽0.024). Similarly, ERalpha protein levels were 100% higher in FE compared to ME on day 14. ERalpha visualized via immunohistochemistry was 1.5 fold higher in FE than ME (p⫽0.028). CONCLUSIONS: This study demonstrates an increase in aortic wall ERalpha in females compared with males that correlates inversely with AAA formation. These findings, coupled with our earlier observation that exogenous estrogen inhibits AAA formation in males, further suggest an important protective role for estrogen during AAA formation.
Bilayered vascular scaffolds for engineering cellularized small diameter blood vessels Young Min Ju PhD, Jin San Choi MS, Tamer Aboushwareb MD, PhD, Anthony Atala MD, FACS James Yoo MD, PhD, Sang Jin Lee PhD Wake Forest University, Winston-Salem, NC INTRODUCTION: Vascular scaffolds fabricated by electrospinning techniques provide adequate structural support as well as accommodation of endothelial (EC) and smooth muscle cells (SMC). How-
Surgical Forum Abstracts
J Am Coll Surg
⫹/⫺ 0.17 MPa), using an equivalence threshold (difference) of 0.24 MPa (p ⫽ .01). While peak wall stress and maximal diameter were correlated for FAs (r ⫽ .90), the correlation for SAs was less robust (r ⫽ .58).
These data provide mechanistic insight into this potentially devastating complication and suggest a potential therapeutic target.
CONCLUSIONS: Although the SAs were smaller than the FAs, mean peak wall stress was equivalent. In addition, maximum diameter and wall stress were more strongly correlated in FAs. Therefore, factors other than maximum diameter, such as aneurysm shape, may result in small SAs having a rupture risk equivalent to larger FAs. These results provide a rationale for the repair of small saccular descending thoracic aortic aneurysms.
Increased estrogen receptor alpha expression in experimental aortic aneurysms in females compared with males
Paralysis following thoracic aortic stenting is associated with endothelial nitric oxide synthase phosphorylation and nitric oxide production
INTRODUCTION: Estrogen receptor alpha (ERalpha) has been identified in the vessel wall, offering vasoprotective effects when upregulated. Estrogens are known to mediate the inflammatory mileu, and inflammation has long been associated with abdominal aortic aneurysm (AAA) formation. It has therefore been theorized that increased estrogen receptor in females contributes to their relative resistance to AAAs. This study’s objective was to determine gender differences in ERalpha levels during experimental AAA formation.
Christopher A Durham MD, Steven C Agle MD, Michael M McNally MD, Ashley C Mays BS, Abdel A Abdel-Rahman PhD, Michael C Stoner MD, FACS East Carolina University, Greenville, NC INTRODUCTION: Paralysis from spinal cord blood supply interruption after endovascular thoracic aortic repair remains a significant risk. The purpose of this study was to investigate the molecular basis of injury. METHODS: A rabbit model of thoracic endovascular repair was created as follows: animals were treated with aortography alone (control, n⫽7) or covered thoracic aortic stent (n⫽8). Each animal was scored three hours postoperatively by the Tarlov scale from 0 (no movement) to 5 (normal hop). Animals were then euthanized at either 1 or 3 hours postoperatively. In a subset of animals intracellular nitric oxide (NO) and superoxide production in thoracic spinal cord sections were investigated with 4-amino-5-methylamino-2⬘,7⬘dilfuorofluorescein (DAF) and dihydroethidium (DHE). A Western blot analysis was performed on both 1 and 3 hour control and stented tissue, and a phosphorylated endothelial nitric oxide synthase (eNOS): eNOS index was determined. RESULTS: Paralysis scores of stented animals were significantly lower than control animals at three hours postoperatively, indicative of severe neurological injury. In the rabbits euthanized at three hours, intracellular nitric oxide production was significantly increased in stented animals. Superoxide production was present in the stented animals; however this did not reach significance. Analysis of the Western blot revealed stented animals had a higher phosphorylated eNOS: eNOS index than controls at both time points (Table, * p⬍0.05, ** p⬍0.01). p-eNOS : eNOS 1° Aortography
30% ⫾ 1%
DHE
Tarlov Score
43.7 ⫾ 4.6
DAF
12.6 ⫾ 2.8
N/A
1° Stent
39% ⫾ 2%**
44.3 ⫾ 4.4
14.6 ⫾ 5.3
N/A
3° Aortography
30% ⫾ 1%
43.9 ⫾ 4.0
13.3 ⫾ 7.9
4.0 ⫾ 0.0
3° Stent
36% ⫾ 2%*
63.0 ⫾ 4.8**
24.7 ⫾ 3.3
1.34 ⫾ 0.8**
CONCLUSIONS: Thoracic aortic stenting is associated with neurological injury, increased phosphorylated eNOS, and NO production.
Adriana Laser MD, MPH, Abhijit Ghosh PhD, Karen J Roelofs DVM, Paul Dimusto MD, Omar Sadiq, Brendan McEvoy BA, Kristopher Barrett Deatrick MD, Jonathan L Eliason MD, Peter K Henke MD, FACS, Gilbert R Upchurch Jr MD, FACS University of Michigan, Ann Arbor, MI
METHODS: Infrarenal aortas of male and female C57 mice (n⫽18 and n⫽16, respectively) were infused with 0.4% elastase. Diameters were measured at day 0 and postoperative day 14. Aortic mRNA expression of ERalpha was determined on day 3 by RTPCR, while ERalpha protein levels were measured via Western blot. Immunohistochemistry using a rabbit antibody for ERalpha was performed on day 14 samples and quantified. Data were compared for significance using a student t-test. RESULTS: Infrarenal aortic diameter increased in elastase-perfused males (ME) by 80% at 14 days post perfusion, while females (FE) increased by only 35% (p⫽0.0012). Paradoxically, FE had 10x greater ERalpha mRNA expression compared with ME (p⫽0.024). Similarly, ERalpha protein levels were 100% higher in FE compared to ME on day 14. ERalpha visualized via immunohistochemistry was 1.5 fold higher in FE than ME (p⫽0.028). CONCLUSIONS: This study demonstrates an increase in aortic wall ERalpha in females compared with males that correlates inversely with AAA formation. These findings, coupled with our earlier observation that exogenous estrogen inhibits AAA formation in males, further suggest an important protective role for estrogen during AAA formation.
Bilayered vascular scaffolds for engineering cellularized small diameter blood vessels Young Min Ju PhD, Jin San Choi MS, Tamer Aboushwareb MD, PhD, Anthony Atala MD, FACS James Yoo MD, PhD, Sang Jin Lee PhD Wake Forest University, Winston-Salem, NC INTRODUCTION: Vascular scaffolds fabricated by electrospinning techniques provide adequate structural support as well as accommodation of endothelial (EC) and smooth muscle cells (SMC). How-