Cell therapy prevents structural, functional and molecular remodeling of remote non- infarcted myocardium Leonardo dos Santos, Giovana A. Gonçalves, Ana.

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Date of download: 5/28/2016 Copyright © The American College of Cardiology. All rights reserved. From: Contractile Function During Angiotensin-II Activation:

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Cell therapy prevents structural, functional and molecular remodeling of remote non- infarcted myocardium Leonardo dos Santos, Giovana A. Gonçalves, Ana Paula Davel, Alexandra A. Santos, José E. Krieger, Luciana V. Rossoni, Paulo J.F. Tucci International Journal of Cardiology Volume 168, Issue 4, Pages 3829-3836 (October 2013) DOI: 10.1016/j.ijcard.2013.06.026 Copyright © 2013 Elsevier Ireland Ltd Terms and Conditions

Fig 1 Repercussions induced by sudden afterload stress in LV maximal rate of pressure rise (+dP/dtmax); stroke volume; cardiac work and LV end-diastolic pressure. Positive or negative values result from relative increase or decrease on that parameter. Sham (n=8); Saline (n=7); BM-MNC (n=7). Values are means±SEM. *P<0.05 vs. Sham; #P<0.05 vs. Saline. International Journal of Cardiology 2013 168, 3829-3836DOI: (10.1016/j.ijcard.2013.06.026) Copyright © 2013 Elsevier Ireland Ltd Terms and Conditions

Fig. 2 In panel A: Original representative recordings of papillary muscles isolated from a Sham-operated rat (Sham), a post-MI injected with cell-free saline solution (Saline), and a post-MI transplanted with bone marrow cells (BM-MNC). Inotropic response to increased Ca2+ (B) or isoproterenol (C) on bath solution. Example record of a stretch–tension protocol (D) and summary data of developed tension (E) and passive tension (F) in response to stretching. Bars represent slopes of the linear regressions. Sham (n=7); Saline (n=6); BM-MNC (n=7). Values are means±SEM. *P<0.05 vs. Sham; #P<0.05 vs. Saline. International Journal of Cardiology 2013 168, 3829-3836DOI: (10.1016/j.ijcard.2013.06.026) Copyright © 2013 Elsevier Ireland Ltd Terms and Conditions

Fig. 3 In panel A: Example record of post-rest potentiation protocol in papillary muscle isolated from a Sham-operated rat. Arrow heads indicate the pauses of stimulation. In B: Effect of increasing pause durations on the relative contraction PRC/SSC (post-rest divided by steady state contraction). Sham (n=7); Saline (n=6); BM-MNC (n=7). Values are means±SEM. *P<0.05 vs. Sham; #P<0.05 vs. Saline. International Journal of Cardiology 2013 168, 3829-3836DOI: (10.1016/j.ijcard.2013.06.026) Copyright © 2013 Elsevier Ireland Ltd Terms and Conditions

Fig. 4 Protein content of sarcoplasmic reticulum Ca2+-ATPase (SERCA2), phospholamban (PLB), phosphorylated phospholamban (Ser16-PLB), α1 and α2 isoforms of Na+, K+-ATPase (NKA), and Na+/Ca2+-exchanger (NCX) on microsomal fractions of reminiscent myocardium from experimental groups. Sham (n=6); Saline (n=6); BM-MNC (n=6). Bars are means±SEM, and lower pictures are example Western blots. *P<0.05 vs. Sham; #P<0.05 vs. Saline. International Journal of Cardiology 2013 168, 3829-3836DOI: (10.1016/j.ijcard.2013.06.026) Copyright © 2013 Elsevier Ireland Ltd Terms and Conditions

Fig. 5 Representative microphotographs of the remote remodeled myocardium stained with (A–C) Periodic acid-Schiff for capillary counting (400× original magnification, arrows indicate some capillaries), and (D–F) eosin–Picrossirius red for interstitial fibrosis evaluation (200× original magnification). Remodeling parameters including myocyte hypertrophy (G–H), capillarity (I–J), and interstitial fibrosis (K) were evaluated in remote myocardial samples from experimental groups. Bars are means±SEM. *P<0.05 vs. Sham; #P<0.05 vs. Saline. International Journal of Cardiology 2013 168, 3829-3836DOI: (10.1016/j.ijcard.2013.06.026) Copyright © 2013 Elsevier Ireland Ltd Terms and Conditions