TY - JOUR
T1 - Enhanced NO Signaling in Patients with Takotsubo Cardiomyopathy: Short-Term Pain, Long-Term Gain?
AU - Nguyen, Thanh
AU - Neil, Christopher
AU - Sverdlov, Aaron
AU - Ngo, Doan
AU - Chan, Wai
AU - Heresztyn, Tamila
AU - Chirkov, Yuliy
AU - Tsikas, Dimitrios
AU - Frenneaux, Michael
AU - Horowitz, John
PY - 2013/12
Y1 - 2013/12
N2 - Purpose Little information is available concerning the mechanism( s) underlying Takotsubo cardiomyopathy (TTC), other than evidence of associated catecholamine secretion. Given the known effects of catecholamines on endothelial function, we tested the hypothesis that TTC might also be associated with impairment of nitric oxide (NO) signaling. We now report an evaluation of NO signaling in TTC patients (vs. aged-matched controls) in relation to (a) severity of the acute attack and (b) rate of recovery. Methods In 56 patients with TTC, we utilized (1) platelet responsiveness to NO and (2) plasma levels of asymmetric dimethylarginine (ADMA) as indices of integrity of the cyclic guanosine monophosphate (cGMP) pathway. Additionally, endothelial progenitor cell (EPC) counts, which are partially NO-dependent, were evaluated. These parameters were measured at the time of diagnosis and 3 months thereafter, and compared with an aging female cohort (n=81). Results The data suggested that both NO generation and effect were accentuated in TTC patients: ADMA concentrations were lower (p=0.003), and responsiveness to NO substantially greater (p=0.0001) than in controls both acutely and after 3 months. Markers of severity of TTC attacks directly correlated with NO responsiveness, while extent of recovery at 3 months varied inversely with ADMA concentrations. Conclusion TTC is associated with intensification of NO signaling relative to that in normal age-matched females. Our data are consistent with this intensified signal's potential contribution to the extent of initial myocardial injury, but conversely to accelerated recovery.
AB - Purpose Little information is available concerning the mechanism( s) underlying Takotsubo cardiomyopathy (TTC), other than evidence of associated catecholamine secretion. Given the known effects of catecholamines on endothelial function, we tested the hypothesis that TTC might also be associated with impairment of nitric oxide (NO) signaling. We now report an evaluation of NO signaling in TTC patients (vs. aged-matched controls) in relation to (a) severity of the acute attack and (b) rate of recovery. Methods In 56 patients with TTC, we utilized (1) platelet responsiveness to NO and (2) plasma levels of asymmetric dimethylarginine (ADMA) as indices of integrity of the cyclic guanosine monophosphate (cGMP) pathway. Additionally, endothelial progenitor cell (EPC) counts, which are partially NO-dependent, were evaluated. These parameters were measured at the time of diagnosis and 3 months thereafter, and compared with an aging female cohort (n=81). Results The data suggested that both NO generation and effect were accentuated in TTC patients: ADMA concentrations were lower (p=0.003), and responsiveness to NO substantially greater (p=0.0001) than in controls both acutely and after 3 months. Markers of severity of TTC attacks directly correlated with NO responsiveness, while extent of recovery at 3 months varied inversely with ADMA concentrations. Conclusion TTC is associated with intensification of NO signaling relative to that in normal age-matched females. Our data are consistent with this intensified signal's potential contribution to the extent of initial myocardial injury, but conversely to accelerated recovery.
KW - Asymmetric dimethylarginine
KW - Nitric oxide signaling
KW - Platelet responsiveness to NO
KW - Takotsubo cardiomyopathy
UR - http://www.scopus.com/inward/record.url?scp=84892365821&partnerID=8YFLogxK
U2 - 10.1007/s10557-013-6481-x
DO - 10.1007/s10557-013-6481-x
M3 - Article
VL - 27
SP - 541
EP - 547
JO - CARDIOVASCULAR DRUGS AND THERAPY
JF - CARDIOVASCULAR DRUGS AND THERAPY
SN - 0920-3206
IS - 6
ER -