Potential advantages of cell administration on the inflammatory response compared to standard ACE inhibitor treatment in experimental myocardial infarction.
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)1beta, IL-6, tumor necrosis factor (TNF)alpha 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 ; TNFalpha inversely correlated with LV fractional shortening.


CONCLUSIONS
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.
Ciulla
Michele M
MM
Istituto di Medicina Cardiovascolare, Centro di Fisiologia Clinica e Ipertensione, University of Milan, Italy. michele.ciulla@unimi.it
Montelatici
Elisa
E
Ferrero
Stefano
S
Braidotti
Paola
P
Paliotti
Roberta
R
Annoni
Giuseppe
G
De Camilli
Elisa
E
Busca
Giuseppe
G
Chiappa
Luisa
L
Rebulla
Paolo
P
Magrini
Fabio
F
Lazzari
Lorenza
L
D000465:Algorithms; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology / Q000502:physiology*; D004195:Disease Models, Animal; D006352:Heart Ventricles / Q000473:pathology; D007249:Inflammation / Q000209:etiology / Q000628:therapy*; D008297:Male; D009203:Myocardial Infarction / Q000097:blood / Q000150:complications / Q000473:pathology / Q000628:therapy*; D011897:Random Allocation; D051381:Rats; D011916:Rats, Inbred F344; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D000806:Angiotensin-Converting Enzyme Inhibitors; D014409:Tumor Necrosis Factor-alpha