Reprogramming the Endocardium
Trials and Tribulations
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- coronary vessels
- embryonic structures
- myocardial infarction
Normal cardiac function is heavily dependent on effective coronary circulation. Coronary perfusion abnormalities, congenital or, much more commonly, acquired, are the leading cause of cardiovascular morbidity and mortality. Despite many advances in our understanding of fundamentals of heart and blood vessel biology, therapeutic options for patients with advanced coronary artery disease are still pretty much limited to mechanical interventions and palliation. Recent discoveries in developmental cardiovascular biology, combined with a better understanding of cellular reprogramming, offer new insights into the origin of coronary vasculature that, perhaps, one day can lead to new therapeutic applications.1
Article, see p 984
The embryonic heart emerges at E7.5 as a cardiac crescent2 and remains avascular until the establishment of coronary circulation after midgestation.3 Although the last few years have witnessed an emergence of a broad outline of key steps involved in formation of the coronary vasculature, many important questions remain. In particular, the origin(s) of coronary endothelial and smooth muscle cells and geographical and temporal specification of their precursors remain the matter of an ongoing debate. Equally important unresolved questions center on what accounts for a relatively high degree of coronary patterning, differences in embryonic versus adult coronary vascular bed growth and regeneration, specification of arterial versus venous endothelial cell identity, and the nature of signaling pathways regulating and guiding coronary vascular growth.
While it is commonly accepted that proepicardium contributes to the development of coronary smooth muscle cell,3,4 the origin of coronary vascular endothelial cells (CVECs) has been long mired in controversy. The advent of Cre-loxP reporter-based lineage tracing techniques has greatly advanced our ability to study developmental cell origins, but these tools are not without their own problems and limitations.3 Data derived from analysis of epicardium-specific Cre mouse lines showed that although …