Migration of Mononuclear Cells Expressing β-Actin Through the Adventitia into Media and Intima in Coronary Arteriogenesis and Venogenesis in Ischemic Myocardium

Abstract

SummaryIt was previously thought that arteriogenesis and venogenesis are induced not only by proliferation of vessel-resident smooth muscle cells (SMCs) and endothelial cells (ECs) but also by migration of their precursors. However, it is not well understood through what route(s) the precursors migrate into the existing vessels.We examined through what route or routes circulating mononuclear cells expressing β-actin (β-MNCs), which we identified in canine coronary vessels, migrate into coronary vessel walls and cause arteriogenesis and venogenesis at 1, 2, 4 and 8 weeks after induction of myocardial infarction.The following changes were observed: (1) The β-MNCs migrated via coronary microvessels to the interstitial space at one week; (2) β-MNCs traversed the adventitia into the media and settled in parallel with pre-existing smooth muscle cells (SMCs) in arterioles and arteries and lost β-actin and acquired α-smooth muscle actin (α-SMA) to become mature SMCs at 2-4 weeks; (3) at the same time, other β-MNCs migrated across the adventitia and media into the intima and settled in parallel with pre-existing endothelial cells (ECs) and lost β-actin, while acquiring CD 31 , to become mature ECs, resulting in arteriogenesis; (4) Similarly, β-MNCs migrated into venular and venous walls and became SMCs or ECs, resulting in venogenesis.β-MNCs in the interstitial space expressed CD 34 but not other major vascular cell markers. β-MNCs, possibly a vascular progenitor, migrate not from the lumen but across the adventitia into the media or intima of coronary vessels and transit to SMCs or ECs, and participate in arteriogenesis and venogenesis in ischemic myocardium. (Int Heart J 2012; 53: 54-63)

Process of Coronary Capillary Tube Formation by Mononuclear Cells Expressing β-Actin in the Ischemic Myocardium

“…They contained CD 34 , indicating a bone marrow origin. β-MNCs however did not contain α-SMA, CD 31 , and vimentin as shown in our previous study [22]. …”

“…In a previous study using the same infarction model in beagles, we found that β-MNCs migrate into the interstitial space and then from outside of the adventitia into the media of the existing arterioles or arteries to become SMCs by loosing β-actin and acquiring α-SMA, and into the intima to become ECs by acquiring CD 31 , indicating that the β-MNCs are multipotent vascular progenitor cells [22].…”

“…These findings indicate that not differentiated ECs but rather β-MNCs, multipotent precursor cells [22], form capillary tubes, and that loss of intracellular granular cytoplasm is the initiating mechanism of capillary tube formation. However, the mechanism of loss of granular cytoplasm remains unclear.…”

“…Although the present study was a spot-to-spot observation and not the observation of the time-course changes in the same β-MNCs, the following process is considered to take place in capillary tube formation: on myocardial infarction production, β-MNCs are recruited to the coronary vessels, especially to capillaries [22]; they sprout out from the pre-existing coronary vessels, adhering to each other in tandem; an intracellular cavity is formed as a consequence of loss of intracellular β-actin-positive granular cytoplasm; intercellular junctions disappear and the cavities connect with each other to form a capillary tube; new β-MNCs are recruited to the terminal end of the capillary tube, migrate outside and adhere to each other in tandem; blood cells drained into the lumen, and these processes are repeated to extend the capillary tube (Figure 7). …”

“…These β-MNCs were present not only in the coronary vessels, but also in the interstitial spaces of the ischemic myocardium. We found that β-MNCs participate in arteriogenesis (formation of arterioles and arteries, and their growth) [22]. Their role in angiogenesis (capillary formation) and how they form coronary capillary tube however remained to be elucidated.…”