Published Online
on August 9, 2004

A more recent version of this article appeared on August 24, 2004

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Submitted on July 8, 2003
Revised on March 16, 2004
Accepted on March 22, 2004

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, and 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.

^* To whom correspondence should be addressed. E-mail: rlee{at}rics.bwh.harvard.edu.

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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