LETTER TO THE EDITOR
NAD(P)H oxidase in the failing human heart
P. A. J. Krijnen, MSc*,
C. Meischl, MD, PhD*,
C. A. Visser, MD, PhD*,
C. E. Hack, MD, PhD*,
H. W. M. Niessen, MD, PhD* and
D. Roos, PhD*
* VU University Medical Center, Department of Pathology, Room 0E16, De Boelelaan 1117, 1007 MB Amsterdam, The Netherlands
paj.krijnen{at}vumc.nl
With great interest we read the recent JACC editorial comment by Warnholtz and Munzel (1) in which they emphasize the importance of NAD(P)H-derived reactive oxygen species in heart failure. This comment was for the greater part inspired by the interesting study by Heymes et al. (2) published in the same issue of JACC, which shows by immunohistochemistry that gp91phox is expressed in human cardiomyocytes.
In their editorial comment, Warnholtz and Munzel state that Heymes et al. (2) for the first time provide evidence of the activation and expression of the NAD(P)H oxidase in human cardiomyocytes. However, in March 2003 we already published a study in which we provided evidence for the expression of gp91phox (Nox2) in human cardiomyocytes (3). This was proven not only by immunohistochemistry but also by Western blot analysis on isolated human cardiomyocytes instead of total-tissue homogenates.
Although both studies describe the expression of Nox2 in human cardiomyocytes, there are some differences. For example, Heymes et al. (2) show by Western blot on total-tissue homogenates that there is no difference in Nox2 expression between failing and nonfailing hearts, whereas we demonstrated by immunohistochemistry that the number of Nox2-expressing cardiomyocytes within the infarction area is significantly increased after acute myocardial infarction (AMI). We have to keep in mind, however, that with AMI we have studied an acute phenomenon, whereas congestive heart failure (CHF) is a more or less chronic process. This might explain the interesting differences in the pattern of Nox2 expression between acute and chronic heart disease and could point to a different regulation of Nox2 expression in both phenomena.
The data of Heymes et al. (2) therefore, corroborate our own findings in that we both, using different antibodies, show that Nox2 is expressed in human cardiomyocytes. Their measured increase in NAD(P)H oxidase activity after CHF and our increased Nox2 expression after AMI emphasize the role of the NAD(P)H oxidase(s) in human cardiovascular pathophysiology. We completely agree with Warnholtz and Munzel that the possible co-expression of other Nox isoforms, the functional contribution of the cardiomyocyte-specific oxidases to the ROS-mediated effects observed in cardiac tissue homogenates, and the search for possibilities of pharmacological intervention are important issues that need to be addressed now.
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References
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1. Warnholtz A, Munzel T. The failing human heart: Another battlefield for the NAD(P)H oxidase? J Am Coll Cardiol. 2003;41:2172–2174[Free Full Text]
2. Heymes C, Bendall JK, Ratajczak P, et al. Increased myocardial NADPH oxidase activity in human heart failure. J Am Coll Cardiol. 2003;41:2164–2171[Abstract/Free Full Text]
3. Krijnen PA, Meischl C, Hack CE, et al. Increased Nox2 expression in human cardiomyocytes after acute myocardial infarction. J Clin Pathol. 2003;56:194–199[Abstract/Free Full Text]
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