Right ventricular effects of intracoronary delivery of mesenchymal stem cells (MSC) in an animal model of pressure overload heart failure.
In a rat model of left ventricular pressure overload hypertrophy with biventricular failure, we studied the effects of intracoronary delivery of mesenchymal stem cells (MCS) upon right ventricular hemodynamic performance, profiles of local inflammation and apoptosis, and determinants of extracellular matrix remodeling. Sprague-Dawley rats underwent aortic banding and were followed by echocardiography. After a decrease in left ventricular fractional shortening of 25% from the baseline (relative 50% reduction), animals were randomized to an intracoronary injection of MSC (n=28) or PBS (n=20). Right ventricular hemodynamic assessment and measurement of local inflammatory markers, proapoptotic factors, and determinants of extracellular matrix remodeling were performed on post-transplantation day 7, 14, 21 or 28. MSC injection improved right ventricular systolic function in the MSC group compared to the control group (mean+/-SD, max dP/dt 772+/-272 mm Hg/s vs. 392+/-132 at 28 days, P<0.01). Diastolic function was similarly improved (mean+/-SD, max -dP/dt -558+/-171 mm Hg/s vs. -327+/-131 at 28 days, P<0.05). Right ventricular levels of IL-1, IL-6, TNF-alpha, bax, bak and p38 were significantly decreased in the MSC treated animals. Expression of MMP-3, MMP-6, MMP-9, TIMP-1 and TIMP-3 declined in the MSC group compared with controls after 28 days. In this model of left ventricular pressure overload hypertrophy and biventricular failure, intracoronary delivery of MSC was associated with an improvement in the right ventricular hemodynamic performance, profiles of local inflammation and apoptosis, and determinants of extracellular matrix remodeling.
Molina
Ezequiel J
EJ
Division of Cardiac and Thoracic Surgery, Temple University School of Medicine, Philadelphia, PA 19140, USA.
Palma
Jon
J
Gupta
Dipin
D
Gaughan
John P
JP
Houser
Steven
S
Macha
Mahender
M
D000818:Animals; D017209:Apoptosis; D004195:Disease Models, Animal; D004452:Echocardiography; D005109:Extracellular Matrix / Q000378:metabolism; D006333:Heart Failure / Q000503:physiopathology / Q000628:therapy*; D006439:Hemodynamics; D017379:Hypertrophy, Left Ventricular / Q000150:complications / Q000503:physiopathology / Q000628:therapy*; D007249:Inflammation / Q000503:physiopathology / Q000628:therapy; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016278:Ventricular Function, Right; D017725:Ventricular Pressure; D020257:Ventricular Remodeling