Pericardial Mesoderm Generates a Population of Coronary Smooth Muscle Cells Migrating into the Heart along with Ingrowth of the Epicardial Organ

Abstract

The vascular smooth muscle cells of coronary arteries are distinguished from those of the proximal aorta by a number of structural and functional criteria which may include an increased propensity for atherosclerotic transformation. At present, the source of this variation between smooth muscle subpopulations is uncertain. Whilst smooth muscle of the proximal aorta is thought to be derived from neural crest, the origin of coronary vascular smooth muscle remains uncharacterized. We have previously shown that precursors of the coronary vasculature enter the tubular heart on the same day as the epicardial mantle starts to envelop the myocardium and that coronary vessels form by ingrowth of these migratory precursors and not by outgrowth from the aorta (Mikawa and Fischman, 1992). To study the origin of coronary smooth muscle cells, the proepicardial organ, from which epicardial cells arise, was tagged with either a vital dye (DiI) or replication-defective retroviruses encoding beta-galactosidase. Cellular lineage marking was achieved by either direct targeting of putative vasculogenic cells in the proepicardium in ovo or tagging dissected proepicardial cells in vitro followed by transplantation to stage-matched host embryos. Monitoring of tagged cells during coronary vasculogenesis indicate incorporation of proepicardial-derived cells into three vessel-associated populations; coronary smooth muscle, perivascular connective tissue, and endothelial cells. Immunoconfocal microscopy identified both endothelial and smooth muscle cell populations within the proepicardial organ. The results demonstrate that: (1) the proepicardium contains a progenitor population of coronary smooth muscle cells that migrates into the heart along with ingrowth of the epicardium and (2) prior to the migration, the coronary smooth muscle lineage is established.

Vasculogenesis of the embryonic heart: Origin of blood island‐like structures

“…The proepicardium is generally known as the precursor of the epicardial mesothelium, which, after mesenchymal transformation, gives rise to cellular components of the coronary vasculature (Mikawa and Gourdie, 1996;Muñ ozChá puli et al, 1996, 2002Dettmann et al, 1998;Gittenberger-de Groot et al, 1998;Pérez-Pomares et al, 2002;Poelmann et al, 2002). The proepicardium has also been acknowledged as having a potential to deliver endothelial cell precursors when transplanted to fetal liver (Pérez-Pomares et al, 2004).…”

“…Some cells of the epicardial mesothelium possess the ability to migrate to the subepicardial space undergoing epicardial-mesenchymal transformation. These mesenchymal cells are considered to be a source of smooth muscle cells that make up the tunica media of coronary vasculature and interstitial fibroblasts as well as fibroblasts of the adventitia (Mikawa and Gourdie, 1996;Dettman et al, 1998;Gittenberger-de Groot et al, 1998;Vrancken Peeters et al, 1999;Wada et al, 2003). Subepicardial space, particularly at the atrioventricular and interventricular sulcuses, is filled with blood cells, angioblasts, mesenchymal cells, and extracellular matrix material (Virá gh et al, 1993;Ká lmá n et al, 1995).…”

“…One theory claims that endothelial cells derive from liver primordium/sinus venosus region and are transported via proepicardium to the heart's surface (Poelmann et al, 1993(Poelmann et al, , 2002. According to the other theory, endothelial cells derive from mesenchymal cells after epithelial-mesenchymal transformation of the epicardial mesothelium (Mikawa and Gourdie 1996;Muñ oz-Chá puli et al, 1999, 2002Pérez-Pomares et al, 2002). Although both theories have accumulated some experimental evidence, the derivation of endothelial cells within the embryonic heart is ambiguous.…”

The Development of the Epicardium in the Sturgeon Acipenser naccarii

“…A feature common to all the species studied is that, following myocardial covering, part of the epicardial cells colonize the space between the epicardium and the myocardium and transform into mesenchyme (Icardo et al, 1990). At subsequent developmental stages, epicardium-derived cells invade the myocardium giving rise to coronary endothelial and smooth muscle cells, cardiac fibroblasts, and blood progenitors (Mikawa and Gourdie, 1996;Pérez-Pomares et al, 1998, 2002Gittenberger-de Groot et al, 1998;Dettman et al, 1998;Männer, 1999;Vrancken Peeters et al, 1999;Pérez-Pomares et al, 2003) (reviewed in Muñ oz-Chápuli et al, 2002;Wessels and Pérez-Pomares, 2004). Epicardium-derived cells also contribute to valve development and to the formation of the fibrous heart skeleton (Gittenbergerde Groot et al, 1998;Lie-Venema et al, 2008).…”

Transplantation Induced Functional/Morphological Changes in Rat Aorta Allografts Differ from Those in Arteries of Rat Kidney Allografts

“…At least two main hypotheses can be drawn from the literature. On the one hand, it may reflect the high degree of phenotypic heterogeneity that is seen within the vascular SMCs in different segments of the arterial tree (23). For example, phenotypic differences between vascular SMCs were proposed to explain why a greater incidence of arteriosclerotic plaque was seen in dog abdominal vs. thoracic aorta homografts (24).…”