Tài liệu Báo cáo khoa học: Brain angiogenesis in developmental and pathological processes:

MINIREVIEW

Brain angiogenesis in developmental and pathological

processes: regulation, molecular and cellular

communication at the neurovascular interface

Hye Shin Lee1,2, Jiyeon Han1,2, Hyun-Jeong Bai1,2 and Kyu-Won Kim1,2,3

1 Neurovascular Coordination Research Center, College of Pharmacy, Seoul National University, Korea

2 Research Institute of Pharmaceutical Science, Seoul National University, Korea

3 Department of Molecular Medicine and Biopharmaceutical Sciences, Seoul National University, Korea

Development of the brain vasculature

Blood vessels form via two distinct processes: vasculo￾genesis and angiogenesis. Vasculogenesis involves the

proliferation and differentiation of mesoderm-derived

angioblasts into endothelial cells [1]. Before the heart

even begins to beat, the primary vascular plexus is

formed throughout the body by vasculogenesis [2]. The

extracerebral vascular plexus is established by vasculo￾genesis within the brain vasculature [2]. Early in

embryogenesis, angioblasts invade the head region and

form the perineural vascular plexus, which ultimately

covers the entire neural tube [3]. After the primary vas￾cular plexus is formed by vasculogenesis, a more com￾plex vascular network is established via angiogenesis

(i.e. the production of vessel branches from pre-exist￾ing vessels). Indeed, the vascular network of the brain

is predominantly formed by angiogenesis. During this

Keywords

astrocyte; barriergenesis; blood–brain

barrier; brain angiogenesis; endothelial cell;

neuron; neurovascular interface; pericyte;

perivascular macrophage; smooth muscle

cell

Correspondence

K.-W. Kim, Neurovascular Coordination

Research Center, College of Pharmacy,

Seoul National University, Seoul 151-742,

Korea

Fax: +82 2 885 1827

Tel: +82 2 880 6988

E-mail: [email protected]

(Received 19 February 2009, revised 6 May

2009, accepted 10 June 2009)

doi:10.1111/j.1742-4658.2009.07174.x

The vascular network of the brain is formed by the invasion of vascular

sprouts from the pia mater toward the ventricles. Following angiogenesis

of the primary vascular network, brain vessels experience a maturation pro￾cess known as barriergenesis, in which the blood–brain barrier is formed.

In this minireview, we discuss the processes of brain angiogenesis and bar￾riergenesis, as well as the molecular and cellular mechanisms underlying

brain vessel formation. At the molecular level, angiogenesis and barriergen￾esis occur via the coordinated action of oxygen-responsive molecules (e.g.

hypoxia-inducible factor and Src-suppressed C kinase substrate ⁄AKAP12)

and soluble factors (e.g. vascular endothelial growth factor and angiopoie￾tin-1), as well as axon guidance molecules and neurotrophic factors. At the

cellular level, we focus on neurovascular cells, such as pericytes, astrocytes,

vascular smooth muscle cells, neurons and brain macrophages. Each cell

type plays a unique role, and works with other types to maintain environ￾mental homeostasis and to respond to certain stimuli. Taken together, this

minireview emphasizes the importance of the coordinated action of mole￾cules and cells at the neurovascular interface, with regards to the regulation

of angiogenesis and barriergenesis.

Abbreviations

Ang-1, angiopoietin-1; AQP4, aquaporin4; BBB, blood–brain barrier; BDNF, brain-derived neurotrophic factor; CNS, central nervous system;

HIF, hypoxia-inducible factor; NGF, nerve growth factor; NT, neurotrophins; SEMA, semaphorin; SSeCKS, Src-suppressed C kinase

substrate; TGF, transforming growth factor; VEGF, vascular endothelial growth factor; VEGFR, vascular endothelial growth factor receptor;

vSMC, vascular smooth muscle cell.

4622 FEBS Journal 276 (2009) 4622–4635 ª 2009 The Authors Journal compilation ª 2009 FEBS