Microscopic observations on the extra‐endothelial cells of living mammalian blood vessels

Abstract

INTRODUOTIONThe growth of new blood vessels in the living mammal, as observed in transparent chambers installed in the ears of rabbits, has been studied microscopically and described in detail ( Sandison, '28 ; Clark et al., '31 ; Clark and Clark, '39).Briefly, it was found that new capillaries arose as endothelial outgrowths from preexisting vascular endothelium, which advanced as blindly ending sprouts, anastomosed with neighboring sprouts to form loops and continued to advance as a plexus with a growing edge of new sprouts. Although the pattern of the new vascular network in each chamber, like that of the intact ear, was different, in standard round table chambers of uniform size and controlled thickness, the tempo at which new capillaries entered the observation space (average of 7 days after the operation) and the rate at which they advanced across it (0.2 to 0.65 mm. per diem) were relatively uniform.The primitive form of the growing vascular network was at first that of an indifferent capillary plexus but as it continued to advance the older portions of the plexus near the table edge soon showed differentiation of vessels receiving a greater supply and drainage into arterioles and venules. Simultaneously, many of the intervening capillaries retracted and disappeared. Vascularization of the table space was usually complete at 2 to 3 weeks after the operation when the sprouts from opposite sides of the table met and anastomosed.

Optimality in the developing vascular system: Branching remodeling by means of intussusception as an efficient adaptation mechanism

“…Further evidence for the essential role played by blood flow in IBR is furnished by Clark and Clark (1940). The latter authors demonstrated that vessel complexity could be increased by the formation of multiple "secondary loops" after an inflammation-induced enhancement of blood flow.…”

Intussusceptive angiogenesis and its role in vascular morphogenesis, patterning, and remodeling

“…During development, sensitivity to the local hemodynamic environment facilitates assembly and remodeling of appropriate microvascular network structures and may continue to be critical in maintaining and remodeling capillary networks in adulthood [51]. The essential role played by hemodynamics was demonstrated many decades ago by Clarke and Clarke [52] when they illustrated increase in vessel complexity as a result of enhanced blood flow subsequent to inflammation. The latter authors showed that such an alteration in hemodynamics resulted in formation of secondary loops and that the vasculature reverted to the simple architecture after relief from inflammation (Fig.…”

“…VEGF is essential for early blood vessel formation and mice deficient in VEGF gene die early during embryogenesis with severe defects in blood vessel formation [63,64]. In contrast, Ang-1 is necessary for later stages of vessel development, and mice with deficiency die of problems associated with vessel [52] remodeling and maturation [57]. Future studies on molecular control of intussusceptive angiogenesis are persuaded to focus on the interactions between angiogenic growth factors (especially VEGF), angiopoetins and their cognate receptors.…”

Apoptosis During Cardiovascular Development

“…In 1918, Clark 69 had argued that all endothelial cells of regressing embryonic vessels retracted into neighboring vessels; however, he later described degeneration and "disappearance" of smooth muscle in these vessels. 70 Early descriptions of ultrastructurally identifiable apoptosis of endothelial cells were based on TEM showing vascular changes in the regressing corpus luteum 71 ; however, there has subsequently been surprisingly few studies of the role of cell death in vascular development.…”