- Email: [email protected]
Androgens Promote Endothelial Progenitor Cell (EPC) Mobilisation in Response to Ischaemia
S10
Heart, Lung and Circulation 2012;21:S1–S142
CSANZ 2012 Abstracts
ABSTRACTS
21 Acute Reversal of Chronic Atrial Stretch is Associated Left Atrial Endothelial Dysfunction C. Schultz 1,∗ , S. Willoughby 1 , S. Kumar 2 , P. Shenbaga 2 , G. Joseph 2 , S. Chandran 2 , A. Srivastava 2 , S. Chandy 2 , B. John 2 , P. Sanders 1 1 Centre
for Heart Rhythm Disorders, University of Adelaide, Royal Adelaide Hospital, Australia 2 Christial Medical College, Vellore, India Introduction: Chronic atrial stretch is associated with a heightened risk of atrial fibrillation (AF) and thrombosis. Asymmetrical dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase (NOS), which leads to decreased nitric oxide (NO) levels, and produces endothelial dysfunction. Elevated ADMA levels are also linked to increased thrombotic risk. Therefore we investigated ADMA levels between peripheral and cardiac sites in chronic atrial stretch due to mitral stenosis and immediately after stretch reversal by balloon mitral valvuloplasty (BMV). Methods: Nineteen patients with mitral stenosis (32 ± 8 years, 8 males) in sinus rhythm undergoing a BMV were studied. Blood samples were withdrawn from the femoral vein (FV), right atria (RA) and left atria (LA) at the start of procedure and then again at the completion of the valvuloplasty. Plasma levels of ADMA were measured as a marker of endothelial dysfunction by conventional ELISA. Results: BMV was successful in all patients. There was no significant difference in ADMA levels between sampling sites at the beginning of the procedure (figure = 0.5). Following BMV there was a dramatic 80-fold increase in LA ADMA levels compared to the FV and RA (p < 0.0001).
culating EPCs are decreased in hypogonadal men, and increased with testosterone treatment, suggesting a role for androgens in EPC-mediated angiogenesis. This study investigated the role of androgens in EPC mobilisation following ischaemia. Methods: Male C57Bl/6J mice were castrated two weeks prior to the induction of unilateral hindlimb ischaemia (HLI) and implanted with a DHT or placebo implant. Laser Doppler Perfusion Imaging (LDPI) was performed to assess flow recovery. Mice were sacrificed and EPCs were harvested from blood, bone marrow and spleen. Sca1+/CXCR4+ EPCs were enumerated using flow cytometry and colony forming unit (CFU) progenitors were assessed using a methylcelluose based assay. Adductor muscle from the ischaemic and non-ischaemic limbs were harvested for qRT-PCR and western blotting. Results: Following HLI, animals given DHT showed significantly increased LDPI flow recovery vs. placebo treated mice (P < 0.05). Sca1+/CXCR4+ EPCs isolated from blood and bone marrow three days post-HLI were greater in DHT treated mice compared with those administered a placebo (P < 0.05). Spleen Sca1+/CXCR4+ cells were not significantly different between groups. The number of CFU progenitors from blood and bone marrow were greater in DHT treated mice than in placebo (P < 0.05). No significant difference in spleen CFU progenitor colonies were observed between treatment groups. Differences in pro-angiogenic factors were observed between DHT and placebo treated mice. Conclusion: This study demonstrates that DHT is efficient in enhancing EPC mobilisation and pro-angiogenic factors following ischaemic injury. http://dx.doi.org/10.1016/j.hlc.2012.05.032 23 Aorto-Coronary Haemodynamics: Aortic Distensibility and Coronary Flow Reserve A. Nelson 1,∗ , R. Puri 1 , J. Cameron 2 , B. Dundon 1,2 , J. Richardson 1 , D. Wong 1,2 , S. Worthley 1 , M. Worthley 1 1 Cardiovascular
Conclusion: Acute reversal of chronic atrial stretch is associated with a significant increase in LA ADMA levels; potentially resulting in a hypercoaguable state. http://dx.doi.org/10.1016/j.hlc.2012.05.031 22 Androgens Promote Endothelial Progenitor Cell (EPC) Mobilisation in Response to Ischaemia L. Lecce 1,∗ , M. Lam 1 , M. Ng 1,2 1 Heart 2 Royal
Research Institute, Australia Prince Alfred Hospital, Australia
Background: The role of androgens in angiogensis has received little attention compared to the extensively researched female counterpart, oestrogen. In humans, cir-
Research Centre, Royal Adelaide Hospital, Australia 2 Monash Cardiovascular Research Centre, Monash Medical Centre, Australia Background: Large artery stiffness has been strongly linked to an increased risk for major adverse cardiac events, with impaired diastolic coronary perfusion believed to be the key mechanistic factor. We undertook to determine, for the first time, the relationship between coronary blood flow and regional aortic distensibility, utilising gold standard invasive techniques and the latest advances in cardiovascular magnetic resonance imaging. Methods: Patients with no significant atheroma on coronary angiography were investigated. Doppler flow wire assessment of the study vessel was performed with measurement of average peak velocity (APV) at rest and during hyperaemia induced by intracoronary infusion of adenosine. Coronary flow reserve (CFR = APVmax/APVrest)
Heart, Lung and Circulation 2012;21:S1–S142
CSANZ 2012 Abstracts
ABSTRACTS
21 Acute Reversal of Chronic Atrial Stretch is Associated Left Atrial Endothelial Dysfunction C. Schultz 1,∗ , S. Willoughby 1 , S. Kumar 2 , P. Shenbaga 2 , G. Joseph 2 , S. Chandran 2 , A. Srivastava 2 , S. Chandy 2 , B. John 2 , P. Sanders 1 1 Centre
for Heart Rhythm Disorders, University of Adelaide, Royal Adelaide Hospital, Australia 2 Christial Medical College, Vellore, India Introduction: Chronic atrial stretch is associated with a heightened risk of atrial fibrillation (AF) and thrombosis. Asymmetrical dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase (NOS), which leads to decreased nitric oxide (NO) levels, and produces endothelial dysfunction. Elevated ADMA levels are also linked to increased thrombotic risk. Therefore we investigated ADMA levels between peripheral and cardiac sites in chronic atrial stretch due to mitral stenosis and immediately after stretch reversal by balloon mitral valvuloplasty (BMV). Methods: Nineteen patients with mitral stenosis (32 ± 8 years, 8 males) in sinus rhythm undergoing a BMV were studied. Blood samples were withdrawn from the femoral vein (FV), right atria (RA) and left atria (LA) at the start of procedure and then again at the completion of the valvuloplasty. Plasma levels of ADMA were measured as a marker of endothelial dysfunction by conventional ELISA. Results: BMV was successful in all patients. There was no significant difference in ADMA levels between sampling sites at the beginning of the procedure (figure = 0.5). Following BMV there was a dramatic 80-fold increase in LA ADMA levels compared to the FV and RA (p < 0.0001).
culating EPCs are decreased in hypogonadal men, and increased with testosterone treatment, suggesting a role for androgens in EPC-mediated angiogenesis. This study investigated the role of androgens in EPC mobilisation following ischaemia. Methods: Male C57Bl/6J mice were castrated two weeks prior to the induction of unilateral hindlimb ischaemia (HLI) and implanted with a DHT or placebo implant. Laser Doppler Perfusion Imaging (LDPI) was performed to assess flow recovery. Mice were sacrificed and EPCs were harvested from blood, bone marrow and spleen. Sca1+/CXCR4+ EPCs were enumerated using flow cytometry and colony forming unit (CFU) progenitors were assessed using a methylcelluose based assay. Adductor muscle from the ischaemic and non-ischaemic limbs were harvested for qRT-PCR and western blotting. Results: Following HLI, animals given DHT showed significantly increased LDPI flow recovery vs. placebo treated mice (P < 0.05). Sca1+/CXCR4+ EPCs isolated from blood and bone marrow three days post-HLI were greater in DHT treated mice compared with those administered a placebo (P < 0.05). Spleen Sca1+/CXCR4+ cells were not significantly different between groups. The number of CFU progenitors from blood and bone marrow were greater in DHT treated mice than in placebo (P < 0.05). No significant difference in spleen CFU progenitor colonies were observed between treatment groups. Differences in pro-angiogenic factors were observed between DHT and placebo treated mice. Conclusion: This study demonstrates that DHT is efficient in enhancing EPC mobilisation and pro-angiogenic factors following ischaemic injury. http://dx.doi.org/10.1016/j.hlc.2012.05.032 23 Aorto-Coronary Haemodynamics: Aortic Distensibility and Coronary Flow Reserve A. Nelson 1,∗ , R. Puri 1 , J. Cameron 2 , B. Dundon 1,2 , J. Richardson 1 , D. Wong 1,2 , S. Worthley 1 , M. Worthley 1 1 Cardiovascular
Conclusion: Acute reversal of chronic atrial stretch is associated with a significant increase in LA ADMA levels; potentially resulting in a hypercoaguable state. http://dx.doi.org/10.1016/j.hlc.2012.05.031 22 Androgens Promote Endothelial Progenitor Cell (EPC) Mobilisation in Response to Ischaemia L. Lecce 1,∗ , M. Lam 1 , M. Ng 1,2 1 Heart 2 Royal
Research Institute, Australia Prince Alfred Hospital, Australia
Background: The role of androgens in angiogensis has received little attention compared to the extensively researched female counterpart, oestrogen. In humans, cir-
Research Centre, Royal Adelaide Hospital, Australia 2 Monash Cardiovascular Research Centre, Monash Medical Centre, Australia Background: Large artery stiffness has been strongly linked to an increased risk for major adverse cardiac events, with impaired diastolic coronary perfusion believed to be the key mechanistic factor. We undertook to determine, for the first time, the relationship between coronary blood flow and regional aortic distensibility, utilising gold standard invasive techniques and the latest advances in cardiovascular magnetic resonance imaging. Methods: Patients with no significant atheroma on coronary angiography were investigated. Doppler flow wire assessment of the study vessel was performed with measurement of average peak velocity (APV) at rest and during hyperaemia induced by intracoronary infusion of adenosine. Coronary flow reserve (CFR = APVmax/APVrest)