Vascular basement membrane components in angiogenesis--an act of balance

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.