Research

Potential advantages of cell administration on the inflammatory response compared to standard ACE inhibitor treatment in experimental myocardial infarction

Michele M Ciulla^1,2 , Elisa Montelatici^2,3 , Stefano Ferrero⁴ , Paola Braidotti⁴ , Roberta Paliotti^1,2 , Giuseppe Annoni^1,2 , Elisa De Camilli⁴ , Giuseppe Busca^1,2 , Luisa Chiappa^1,2 , Paolo Rebulla² , Fabio Magrini^1,2 and Lorenza Lazzari^2,3

¹  Istituto di Medicina Cardiovascolare, Centro di Fisiologia Clinica e Ipertensione, University of Milan, Italy

²  Fondazione Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, IRCCS, Milan, Italy

³  Cell Factory "Franco Calori", Milan, Italy

⁴  II Cattedra di Anatomia Patologica, University of Milan, DMCO A.O. San Paolo, Milan, Italy

author email corresponding author email

Journal of Translational Medicine 2008, 6:30doi:10.1186/1479-5876-6-30

Published:	12 June 2008

Abstract

Background

Bone Marrow (BM) progenitor cells can target the site of myocardial injury, contributing to tissue repair by neovascolarization and/or by a possible direct paracrine effect on the inflammatory cascade. Angiotensin Converting Enzyme inhibitors (ACE-I) are effective in reducing mortality and preventing left ventricular (LV) function deterioration after myocardial infarction.

Methods

We investigated the short term effects of BM mononuclear cells (BMMNCs) therapy on the pro-inflammatory cytokines (pro-CKs) and on LV remodelling and compared these effects over a standard ACE-I therapy in a rat model of myocardial cryodamage.

Forty two adult inbread Fisher-F344 rats were randomized into three groups: untreated (UT; n = 12), pharmacological therapy (ACE-I; n = 14, receiving quinapril), and cellular therapy (BMMNCs; n = 16, receiving BMMNCs infusion). Rats underwent to a standard echocardiogram in the acute setting and 14 days after the damage, before the sacrifice. Pro-CKs analysis (interleukin (IL)1β, IL-6, tumor necrosis factor (TNF)α was performed (multiplex proteome arrays) on blood samples obtained by direct aorta puncture before the sacrifice; a control group of 6 rats was considered as reference.

Results

Concerning the extension of the infarcted area as well as the LV dimensions, no differences were observed among the animal groups; treated rats had lower left atrial diameters and higher indexes of LV function. Pro-Cks were increased in infarcted-UT rats if compared with controls, and significantly reduced by BMMNCs and ACE-I ; TNFα inversely correlated with LV fractional shortening.

Conclusion

After myocardial infarction, both BMMNCs and ACE-I reduce the pattern of pro-Ck response, probably contributing to prevent the deterioration of LV function observed in UT rats.