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The relationship between cardiac endothelium and fibroblasts: it’s complicated
Ravi Karra, … , Agoston O. Walter, Sean M. Wu
Ravi Karra, … , Agoston O. Walter, Sean M. Wu
Published June 26, 2017
Citation Information: J Clin Invest. 2017;127(8):2892-2894. https://doi.org/10.1172/JCI95492.
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Commentary

The relationship between cardiac endothelium and fibroblasts: it’s complicated

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Abstract

Coronary revascularization is an effective means of treating ischemic heart disease; however, current therapeutic revascularization strategies are limited to large caliber vessels. Because the mammalian heart scars following cardiac injury, recent work showing that cardiac fibroblasts can transdifferentiate into new coronary endothelium raises a new and exciting approach to promoting endogenous revascularization following cardiac injury. In this issue of the JCI, He et al. report on their employment of a battery of lineage-tracing tools to address the developmental origins of fibroblasts that give rise to new endothelial cells. Surprisingly, cardiac fibroblasts did not appear to contribute appreciably to regeneration of cardiac endothelium. Instead, cardiac endothelial cells were likely to proliferate and generate new endothelium following injury. As these conclusions diverge from prior findings, additional work will be required to understand the sources that generate cardiac endothelium in new blood vessels after injury. Clarification of the origins of coronary endothelial cells during cardiac repair is essential for identifying improved approaches to revascularizing damaged myocardium in patients with ischemic heart disease.

Authors

Ravi Karra, Agoston O. Walter, Sean M. Wu

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Figure 1

Divergent models of the source of new cardiac endothelial cells following injury.

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Divergent models of the source of new cardiac endothelial cells followin...
(A) Using a transgenic Col1a2-CreER mouse model, Ubil et al. found that preexisting cardiac fibroblasts contribute 30% to 40% of new endothelial cells following ischemia-reperfusion injury. (B) In this issue, He et al. performed lineage-tracing and dilution experiments in multiple mouse models to characterize the source of new endothelium following ischemia-reperfusion. Surprisingly, Col1a2-, Pdgfra-, or Tcf21-expressing fibroblasts, Sox9-expressing mesenchymal cells, and Postn-expressing myofibroblasts do not contribute to new coronary endothelial cells following injury. However, preexisting Cdh5-, Apln-, or Fabp4-expressing endothelial cells were a major source of new endothelial cells.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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