Immunolocalisation and activity of DDAH I and II in the heart and modification post-myocardial infarctioN

Gray, G. A., Patrizio, M., Sherry, L., Miller, A. A. , Malaki, M., Wallace, A. F., Leiper, J. M. and Vallance, P. (2010) Immunolocalisation and activity of DDAH I and II in the heart and modification post-myocardial infarctioN. Acta Histochemica, 112(5), pp. 413-423. (doi:10.1016/j.acthis.2009.02.009) (PMID:19481782)

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Abstract

Summary: Asymmetric dimethylarginine (ADMA) and NG monomethyl-l-arginine (l-NMMA) are endogenous inhibitors of nitric oxide synthases (NOS) and their local concentration is determined by the activity of dimethylarginine dimethylaminohydrolases (DDAHs). The current study in male Wistar rats was designed to immunolocalise DDAH I and II in relation to NOS and to investigate changes in distribution, activity and ADMA content in the acute period following myocardial infarction (MI) resulting from coronary artery ligation. Seven days after the coronary artery ligation, l-Arg and methylated arginine content, as well as DDAH activity were determined in homogenates of left ventricular (LV) infarct and border. The distribution of immunoreactive DDAH I, DDAH II, eNOS and iNOS were determined in sections of LV. In healthy hearts, DDAH I was absent, however, DDAH II was localized to endothelium and endocardium with a similar distribution to that of eNOS. Following MI, LV DDAH activity was increased (to 210±19% of control, P<0.05). Both DDAH I and DDAH II proteins were detected in peri-infarct cardiomyocytes, while DDAH II immunoreactivity was additionally localized to infiltrating inflammatory cells and blood vessels in the healing infarct. Both plasma and LV concentrations of the DDAH substrate, ADMA, were increased post-MI, although the ratio of Arg:ADMA was retained in the LV post-MI relative to sham operated controls. In conclusion, DDAH II has a distribution similar to eNOS in healthy myocardium. The increased levels and activity of DDAH I and DDAH II enzymes following myocardial infarction suggest a potential role for them in local protection of NOS enzymes from inhibition by methylated arginines during infarct healing.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Miller, Dr Alyson and Leiper, Professor James
Authors: Gray, G. A., Patrizio, M., Sherry, L., Miller, A. A., Malaki, M., Wallace, A. F., Leiper, J. M., and Vallance, P.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Acta Histochemica
Publisher:Elsevier
ISSN:0065-1281
ISSN (Online):1618-0372
Published Online:29 May 2009

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