Building better blood vessels: new insight on the molecular control of arteriogenesis
Authors: A Strauch
Journal: Cardiovascular Research (2003)

See article by Boengler et al. [2] (pages 573-581) insubsequent release of monocyte chemotactic and survival this issue.factors such as MCP-1 and GM-CSF [6].Once inflamma-Our understanding of the initial steps in blood vessel tion begins, a second remodeling phase follows driven by formation has been advanced through studies employing unknown agents but seemingly down-stream of activated transgenic and knock-out mouse models [1] as well as TGFb1 that accumulates within the tunica media through isolated cells cultivated under conditions of altered oxygen the actions of continuously infiltrating monocytes and level and shear stress.From the standpoint of identifying macrophages.Developmentally, TGFb1 has been associbasic biological controls, examination of the tumor vascu-ated with perivascular cell recruitment and neovessel larization process also has provided insight concerning the stabilization through coordinated regulation of genes enmolecular pathways required to form and sustain the coding smooth muscle contractile proteins such as vascular microvasculature.However, much remains to be discov-smooth muscle a-actin and extracellular matrix proteins ered about the far slower, adaptive process of ar-such as type I collagen [1].Mice defective for TGFb1 teriogenesis whereby pre-existing arterioles adopt new have numerous deficiencies associated with poor host structural features required for sustaining blood flow defense responses and microvessel wall weakness.Imaround vascular obstructions.Especially fascinating are portantly, TGFb1 elicited a strong, local arteriogenic molecular events that occur in the vicinity of obstruction response within the rabbit hindlimb collateral circulation points where oxygen levels are near normal but flow rates when infused directly into the obstructed femoral artery significantly altered.An interesting report by Boengler and [4].Boengler et al.[2] extend these observations by colleagues, appearing in this issue of Cardiovascular showing that local infusion of activated TGFb1 into the Research [2], has helped in this regard by identifying links obstructed hindlimb circulation evokes more than a threebetween biomechanical stress and expression of specific fold increase in CARP mRNA expression within a 24 h transcription factors in the arterial wall.Importantly, two period. of these factors, the cardiac ankyrin repeat protein (CARP)What does elevated expression of CARP in the collateral and Egr-1, previously have been implicated in car-bed tell us about the molecular control of arteriogenesis?diovascular diseases associated with both vascular and Currently, our information on the biochemical properties myocardial tissue remodeling [1,3].of this nuclear protein comes primarily from the cardiac Arteriogenesis is proposed to consist of two phases morphogenesis literature where CARP has been identified [4,5].The initiating event appears to be endothelial cell as a negative regulator of ventricular-specific myosin light damage produced by high fluid shear forces generated chain-2 (MLC-2v) gene transcription [3].CARP-mediated through pre-existing collaterals that by-pass flow around an transcriptional repression in the developing mouse heart obstructed vessel segment.Biomechanical stress on the appears to be based on its ability to sequester the YB-1 tunica intima within by-pass vessels promotes inflamma-cold shock domain protein (also known as MSY1) required tory cell adhesion to activated endothelial cells with for MLC-2v promoter activation.Additionally, CARP is a down-stream target of the mammalian Nkx 2.5 gene required for specification of the ventricular chambers and