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(Circulation. 2004;110:962-968.)
© 2004 American Heart Association, Inc.

Original Articles

Endothelial Cells Promote Cardiac Myocyte Survival and Spatial Reorganization

Implications for Cardiac Regeneration

Daria A. Narmoneva, PhD; Rada Vukmirovic, MS; Michael E. Davis, PhD; Roger D. Kamm, PhD; Richard T. Lee, MD

From the Cardiovascular Division (D.A.N., R.V., M.E.D., R.T.L.), Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, and the Division of Biological Engineering, Massachusetts Institute of Technology (D.A.N., R.D.K., R.T.L.), Cambridge, Mass.

Correspondence to Richard T. Lee, MD, Partners Research Facility, Room 279, 65 Landsdowne St, Cambridge, MA 02139. E-mail rlee{at}rics.bwh.harvard.edu

Received July 8, 2003; de novo received December 17, 2003; revision received March 16, 2004; accepted March 22, 2004.

Background— Endothelial–cardiac myocyte (CM) interactions play a key role in regulating cardiac function, but the role of these interactions in CM survival is unknown. This study tested the hypothesis that endothelial cells (ECs) promote CM survival and enhance spatial organization in a 3-dimensional configuration.

Methods and Results— Microvascular ECs and neonatal CMs were seeded on peptide hydrogels in 1 of 3 experimental configurations: CMs alone, CMs mixed with ECs (coculture), or CMs seeded on preformed EC networks (prevascularized). Capillary-like networks formed by ECs promoted marked CM reorganization along the EC structures, in contrast to limited organization of CMs cultured alone. The presence of ECs markedly inhibited CM apoptosis and necrosis at all time points. In addition, CMs on preformed EC networks resulted in significantly less CM apoptosis and necrosis compared with simultaneous EC-CM seeding (P<0.01, ANOVA). Furthermore, ECs promoted synchronized contraction of CMs as well as connexin 43 expression.

Conclusions— These results provide direct evidence for a novel role of endothelium in survival and organization of nearby CMs. Successful strategies for cardiac regeneration may therefore depend on establishing functional CM–endothelium interactions.

Key Words: endothelium • cardiomyopathy • heart failure • tissue

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