Abstract
Background: Capillary tube formation is essential for angiogenesis. It was previously thought that capillary tubes are formed through self-division of pre-existing endothelial cells (ECs) or folding of EC-progenitor cells. We found that circulating mononuclear cells that express β-actin (β-MNCs), participate in arteriogenesis, (formation of arterioles and arteries, and their growth) but it remained obscure whether and how they participate in capillary tube formation. Methods: We induced acute myocardial infarction in beagles, and examined the process of capillary tube formation by β-MNCs in the infarcted myocardium. Results: β-MNCs were recruited to coronary vessels, in particular to capillaries, in the border zone of infarcted myocardium. β-MNC nuclei were either round or flat, indicating existence of several species of β-MNCs. They sprouted out from a pre-existing coronary arteriole, capillary or venule into the interstitial space, and adhered to each other in tandem. An intracellular cavity was formed by the loss of granular cytoplasm in each cell. The intercellular junctions which connected cell-to-cell disappeared, and the cavities connected with each other to form a capillary tube. New β-MNCs moved to the distal end of the tube and migrated outside to extend the capillary tube. ECs of the capillary tubes thus formed possessed CD31, a marker for EC, but not β-actin. Their nuclei were either round or flat, indicating existence of two different capillary tubes. Conclusions: Coronary capillary tube formation in the ischemic myocardium is initiated by β-MNCs, not by their folding but by intracellular cavity formation through the loss of their granular cytoplasm and consequent tube formation by cavity-to-cavity connection.
Highlights
Capillary tube formation is an essential process of angiogenesis
Identify substances that accelerate or inhibit capillary tube formation [612], there has been a dearth of in vivo investigations of the mechanisms of capillary tube formation in ischemic tissues. It remains to be elucidated whether changing shape by endothelial cells (ECs) initiates capillary tube formation, as seen in vitro, and whether and in what way precursor cells participate in capillary tube formation, especially in ischemic tissues in vivo
These β-MNCs were filled with β-actin-positive granular cytoplasm but had no intracellular cavities, indicating that they were immature capillary tubes (Figure 4A, 4B)
Summary
Capillary tube formation is an essential process of angiogenesis. It was previously thought that differentiated endothelial cells (ECs) form capillary tubes by self-division or folding [1,2,3,4,5] (Figure 1). a number of in vitro studies have been performed toA. Capillary tube formation is an essential process of angiogenesis. It was previously thought that differentiated endothelial cells (ECs) form capillary tubes by self-division or folding [1,2,3,4,5] (Figure 1). It remains to be elucidated whether changing shape by ECs initiates capillary tube formation, as seen in vitro, and whether and in what way precursor cells participate in capillary tube formation, especially in ischemic tissues in vivo. Angiogenesis is known to occur [13], and capillary tube formation has been confirmed, in the ischemic myocardium [14]. It was previously thought that capillary tubes are formed through self-division of pre-existing endothelial cells (ECs) or folding of EC-progenitor cells. We found that circulating mononuclear cells that express β-actin (β-MNCs), participate in arteriogenesis, (formation of arterioles and arteries, and their growth) but it remained obscure whether and how they participate in capillary tube formation
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