高级病理生理学 高级病生-血管新生与疾病
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Angiogenesis first described by Dr John Hunter
1990s
1800 1971 1989
Several German pathologists observe that some human tumours are highly vascularised, leading to the
Discovery by Napoleone Ferrara and colleagues of possibly the most important
angiogenic factor, VEGF
1Ferrara. Nat Rev Cancer 2002 6 2Folkman. NEJM 1971
VEGF
Smooth Muscle Cells
Basement Membrane
Endothelium
New Lumen Formation
13
Angiogenesis - Vascular Maturation
VEGF
Smooth Muscle Cells
Basement Membrane
Endothelium
Vasculogenesis Formation of blood vessels by differentiation from (hem)angioblasts
4
Angiogenesis and vasculogenesis
5
Key landmarks in understanding angiogenesis
2
Outline
1- Angiogenesis and vasculogenesis 2- Important factors, receptors and signaling pathways 3- Tumor angiogenesis 4- Angiogenesis-related diseases
Mouse cornea: wounding induces angiogenesis, chemotactic response to angiogenic factors
9
Angiogenesis - Basement Membrane Breakdown
Angiogenic Stimulus (VEGF)
suggestion that the new vessels have an important pathogenic role in the cancer process1
Landmark publication: Judah Folkman proposes tumour growth is angiogenesis-dependent2
பைடு நூலகம்
Nascent Vascular Sprouts
11
Angiogenesis - Endothelial Cell Proliferation
VEGF
Smooth Muscle Cells
Basement Membrane
Endothelium
Sprout Elongation
12
Angiogenesis - Capillary Morphogenesis
Structure of vessels and capillaries
Small artery: Capillary: endothelial cell, basal lamina, pericytes
7
Angiogenesis: Sprouting angiogenesis
8
Angiogenesis: Sprouting angiogenesis
SMC, pericyte recruitment
14
Angiogenesis - Vascular Maturation
Smooth Muscle Cells
Basement Membrane
Endothelium
Endothelial cell-cell junctions
15
Non-Sprouting Angiogenesis (Intussuseptive angiogenesis)
5- Anti-angiogenesis therapies and therapeutic Angiogenesis 6- Angiogenesis assay model
3
Angiogenesis and vasculogenesis
Angiogenesis Sprouting or Non-sprouting of cells from mature endothelial cells of the vessel wall
16
Normal Angiogenesis in Children
17
Normal Angiogenesis in Adults
Angiogenesis in uterine lining
Angiogenesis in tissue during wound healing
Smooth Muscle Cells
Basement Membrane
Endothelium
Proteases
10
Angiogenesis - Endothelial Cell Migration
VEGF
Smooth Muscle Cells
Basement Membrane
Endothelium
ANGIOGENESIS
1
CoCnotnatcatcttotomme e
• 上海市东安路130号西7号楼212室 复旦大学上海医学院生理与病理生理学系 Tel:021-54237392 Email:dmeng@
• Dan Meng, M.D., Associate Professor Department of Physiology & Pathophysiology Fudan University Room 212, West 7 th Building, 130 Dongan Road Shanghai 200032, China. Tel: 86-21-54237392 Email:dmeng@