Enhanced NO Signaling in Patients with Takotsubo Cardiomyopathy: Short-Term Pain, Long-Term Gain?

Thanh Nguyen, Christopher Neil, Aaron Sverdlov, Doan Ngo, Wai Chan, Tamila Heresztyn, Yuliy Chirkov, Dimitrios Tsikas, Michael Frenneaux, John Horowitz

    Research output: Contribution to journalArticlepeer-review

    23 Citations (Scopus)

    Abstract

    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.

    Original languageEnglish
    Pages (from-to)541-547
    Number of pages7
    JournalCARDIOVASCULAR DRUGS AND THERAPY
    Volume27
    Issue number6
    DOIs
    Publication statusPublished - Dec 2013

    Keywords

    • Asymmetric dimethylarginine
    • Nitric oxide signaling
    • Platelet responsiveness to NO
    • Takotsubo cardiomyopathy

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