Vascular Basement Membrane Components in Angiogenesis — An Act of Balance

Lars Jakobsson,Lena Claesson-Welsh

doi:10.1100/tsw.2008.155

Abstract

Angiogenesis is crucial in the progression of a number of pathological conditions, such as diabetic retinopathy, rheumatoid arthritis, psoriasis, and cancer. In contrast to vessels in healthy tissues, the vasculature in these pathologies is highly unstable, constantly dissolving and renewing. Characteristically, vessels in pathologies have discontinuous basement membrane (BM) coverage. The consequences of shifts in BM density and composition are still relatively unknown. Several studies have illustrated that partial loss of the vascular BM during development results in the widening of vessels. This has been suggested to be a result of reduced mechanical resistance to the force inflicted by the blood pressure. However, recent data indicate that depletion of BM laminins (LMs) leads to enlarged vessels even in the absence of cardiac activity and blood pressure. A key question is whether single BM components or fragments thereof play distinct roles in the angiogenic process, or if it is the balance between the different components of the BM that guides the morphology of the new vessel.

Highlights

All endothelial cells (ECs) in the body rest on basement membrane (BM) composed of intricate networks of matrix proteins, such as fibronectins, collagen IV, and LMs
In a recent study[3], we examined the role of BM LMs in the formation of vascular structures in spheroids of differentiating embryonic stem cells, denoted embryoid bodies[9]
Since there is no flow in embryoid bodies, we conclude that widening of the vessel lumen in the absence of LM deposition is not a consequence of decreased resistance to shear stress or blood pressure in this model

Summary

Introduction

All endothelial cells (ECs) in the body rest on BMs composed of intricate networks of matrix proteins, such as fibronectins, collagen IV, and LMs. LMs are heterotrimeric glycoproteins composed of α-, β-, and γ-chains. The lama4-/- (lacking the LM α4-chain) mice suffer from hemorrhages and display enlarged blood vessel width during embryonic and neonatal stages[8]. In a recent study[3], we examined the role of BM LMs in the formation of vascular structures in spheroids of differentiating embryonic stem cells, denoted embryoid bodies[9].

Results

Conclusion