Enhanced NO Signaling in Patients with Takotsubo Cardiomyopathy: Short-Term Pain, Long-Term Gain?
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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.
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).
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.
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.
KeywordsTakotsubo cardiomyopathy Nitric oxide signalling Platelet responsiveness to NO Asymmetric dimethylarginine
- 24.Schiller NB, Shah PM, Crawford M, DeMaria A, Devereux R, Feigenbaum H, et al. Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. American Society of Echocardiography Committee on Standards, Subcommittee on Quantitation of Two-Dimensional Echocardiograms. J Am Soc Echocardiogr. 1989;2:358–67.PubMedGoogle Scholar
- 25.Neil C, Nguyen TH, Kucia A et al. Slowly resolving global myocardial inflammation/oedema in Tako-Tsubo cardiomyopathy: evidence from T2-weighted cardiac MRI. Heart (British Cardiac Society) 2012;98:1278–84.Google Scholar
- 31.Antoniades C, Shirodaria C, Leeson P, Antonopoulos A, Warrick N, Van-Assche T, et al. Association of plasma asymmetrical dimethylarginine (ADMA) with elevated vascular superoxide production and endothelial nitric oxide synthase uncoupling: implications for endothelial function in human atherosclerosis. Eur Heart J. 2009;30:1142–50.PubMedCrossRefGoogle Scholar
- 44.Chong CR, Law G, Neil CJ, Nguyen TH, Horowitz JD. Dissociation between severity of takotsubo cardiomyopathy and presentation with shock or hypotension. Clin Cardiol. 2013;36:401–6.Google Scholar