Abstract
Cardiovascular diseases including coronary artery disease are the leading cause of death worldwide. Unraveling the developmental origin of coronary vessels could offer important therapeutic implications for treatment of cardiovascular diseases. The recent identification of the endocardial source of coronary vessels reveals a heterogeneous origin of coronary arteries in the adult heart. In this review, we will highlight recent advances in finding the sources of coronary vessels in the mammalian heart from lineage-tracing models as well as differentiation studies using pluripotent stem cells. Moreover, we will also discuss how we induce neovascularization in the damaged heart through transient yet highly efficient expression of VEGF-modified mRNAs as a potentially therapeutic delivery platform.
Highlights
It has been reported that heart vessels supply nutrients and oxygen to the heart, and provide regenerative cues in pathological conditions such as coronary artery disease and subsequently myocardial infarction
While Wu et al show that ventricular endocardium is the primary source of intramyocardial coronary vessels using the Nfatc1-Cre lineage-tracing line [14], Tian et al demonstrate that only little ventricular endocardial cells migrate into the myocardium of free ventricular wall in the embryonic heart [10]
Using the Apelin-1-Cre lineage tracing line, it was found that the Apelin-1-derived subepicardial endothelial cells are the major source of intramyocardial coronary vessels in the embryonic heart (E10.5–11.5) which invade the compact myocardium to form coronary arteries and remain on the surface to produce the vein [10]
Summary
It has been reported that heart vessels supply nutrients and oxygen to the heart, and provide regenerative cues in pathological conditions such as coronary artery disease and subsequently myocardial infarction (for review, see [1,2]). The heart muscle does not significantly regenerate, and disease progression from blocked heart vessels in some patients cannot be delayed by medical or surgical interventions, including balloon angioplasty or coronary artery bypass [3]. The regeneration of coronary arteries through stem-cell-based tissue engineering, paracrine-factor-based approaches, or both offers great potential in the treatment of cardiovascular diseases. Together, understanding the developmental origins of coronary vessels in the heart could shed light on novel treatment options for both congenital and adult cardiovascular diseases. Identifying the cellular origins and sources of coronary vessels is essential in tracing development as well as uncovering mechanisms of coronary artery disease and regeneration. We will highlight recent advances in finding the origins and sources of coronary vessels in the heart using lineage-tracing mouse models and pluripotent stem cell tools. We will discuss a potential therapeutic delivery platform via the transient yet highly efficient expression of modified mRNAs for upregulating paracrine factors of interest and inducing neovascularization in the damaged heart
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