DISPARATE ROLES OF TNF AND NO FOR DEVELOPMENT OF ANEMIA IN MURINE MODELS OF HEART FAILURE
Abstract number: O-SUN-1-2
Aim: Ischemic heart failure (CHF) with anemia carries a poor prognosis. Whether anemia develops in non-ischemic CHF is uncertain. The hematopoietic inhibitors TNFa and NO are activated in ischemic CHF. Here we examined if ischemic and non-ischemic CHF mice develop anemia, and the putative roles of TNFa and NO. Methods: We studied mice (n = 7-9 per group) with CHF either due to myocardial infarction (MI, Iversen et al. 2002), or to overexpression of the Ca2+-binder calsequestrin (CSQ, Harding et al. 2001), or to induced cardiac disruption of the sarcoplasmic reticulum Ca2+-ATPase2 gene (SERCA2 KO, Andersson et al. 2009). Hematopoiesis was analyzed by colony formation of CD34+ bone marrow cells. Results: Hemoglobin concentration was 14.0 ± 0.4 g/dl (mean ± SD) in controls, while it was decreased to 10.1 ± 0.4, 9.7 ± 0.4 and 9.6 ± 0.3 g/dl in MI, CSQ and SERCA2 KO, respectively (P < 0.05). Colony numbers per 100,000 CD34+ cells were reduced to 33 ± 3 (MI), 34 ± 3 (CSQ) and 39 ± 3 (SERCA2 KO) compared with 68 ± 4 in controls (P < 0.05). Only in MI plasma TNFa nearly doubled, and addition of anti- TNFa antibody normalized colony formation. Inhibition of colony formation was abolished with blockade of endothelial NO synthase in CSQ and SERCA2 KO, but not in MI. Conclusion: The mechanisms of anemia in CHF depend on its etiology: whereas TNFa impairs hematopoiesis in MI-induced CHF, NO inhibits blood cell formation in non-ischemic CHF. References 1. Andersson, K.B., Birkeland, J.A.K., Finsen, A.V., Louch, W.E., Sjaastad, I., Wang, Y., Chen. J., Molkentin, J.D., Chien, K.R., Sejersted, O.M. & Christensen, G. 2009. J Mol Cell Cardiol 47, 180-187. 2. Harding, V.B., Jones, L.R., Lefkowitz, R.J., Koch, W.J., Rockman, H.A. & Harding, V.B. 2001. Proc Natl Acad Sci U S A 98, 5809-5814 begin_of_the_skype_highlightingend_of_the_skype_highlighting. 3. Iversen, P.O., Woldbaek, P.R., Tonnessen, T. & Christensen, G. 2002. Am J Physiol Regul Integr Comp Physiol 282.