Intussusceptive angiogenesis: pillars against the blood flow

Abstract

Adaptation of vascular networks to functional demands needs vessel growth, vessel regression and vascular remodelling. Biomechanical forces resulting from blood flow play a key role in these processes. It is well-known that metabolic stimuli, mechanical forces and flow patterns can affect gene expression and remodelling of vascular networks in different ways. For instance, in the sprouting type of angiogenesis related to hypoxia, there is no blood flow in the rising capillary sprout. In contrast, it has been shown that an increase of wall shear stress initiates the splitting type of angiogenesis in skeletal muscle. Otherwise, during development, both sprouting and intussusception act in parallel in building the vascular network, although with differences in spatiotemporal distribution. Thereby, in addition to regulatory molecules, flow dynamics support the patterning and remodelling of the rising vascular tree. Herewith, we present an overview of angiogenic processes with respect to intussusceptive angiogenesis as related to local haemodynamics.

Cell behaviors and dynamics during angiogenesis

“…Intussusceptive angiogenesis (also referred to as intussusceptive sprouting) is the process in which a blood vessel splits longitudinally into two (Styp-Rekowska et al, 2011). This event was first reported during rat lung development (Burri et al, 1974).…”

Inhibition of Notch signaling induces extensive intussusceptive neo-angiogenesis by recruitment of mononuclear cells

“…In liver regeneration models and in postpneumonectomy alveolar angiogenesis, intussusception has been identified as the predominant mode of growth, and also in extraembryonic vasculatures including the vitelline circulation, intussusception appears to prevail over sprouting [7][8][9]. Surprisingly, the cellular and molecular regulation of intussusception is less well known, but recent evidence suggests that it might involve components regulated by blood flow and Notch signaling [6,7]. Here, we provide evidence showing that Notch regulates intussusception involving interaction with circulating mononuclear cells in developing vascular networks.…”

“…This results in formation of supplying and draining vessels, pruning of arteries and veins, and finally remodeling of the primitive capillary plexuses. IA is a step process involving intussusceptive microvascular growth, intussusceptive arborization, and intussusceptive remodeling [2,3,5,6]. The processes lead to formation of hierarchically organized and mature vascular networks.…”

Role of Notch, SDF-1 and Mononuclear Cells Recruitment in Angiogenesis

“…The intensive work of our group in the past few decades clearly documented the morphological features of this specific angiogenic mode and demonstrated its definite presence during development and tumorigenesis as a complementary to sprouting vessel growth. Surprisingly, the cellular and molecular regulation of intussusception is less well known but recent evidence suggests that it might involve a component regulated by blood flow and Notch signaling [7,9]. We provided with evidence showing that Notch regulates intussusception involving interaction with circulating mononuclear cells in developing vascular networks [11].…”

“…The effect is the formation of hierarchically organized vessels with supplying and draining function, pruning of arteries, and veins, and finally development of the primitive capillary plexuses into the functional vascular system. IA is a process with several consecutive steps, including intussusceptive microvascular growth, intussusceptive arborization, and intussusceptive remodeling [2,3,6,7]. These processes end in the formation of mature vascular networks.…”