Chapter 7 - Arteriogenesis and angiogenesis

Question 1

Arteriogenesis vs angiogenesis

Answer 1

Arteriogenesis: collateral circulation to bypass obstructed vessel

Angiogenesis: increase capillary density

Question 2

Components of neovascularization

Answer 2

1) vasculogenesis
2) arteriogenesis
3) angiogenesis

Question 3

Vasculogenesis definition

Answer 3

de novo formation of embryonic blood vessels from vascular progenitor cells/hemangioblasts

Question 4

Trigger of arteriogenesis

Answer 4

Narrow artery –> pressure difference –> fluid shear stress –> endothelium activation –> collateral vessel formation

Question 5

Triggers of angiogenesis

Answer 5

Reduced tissue perfusion –> decrease oxygen tension –> increase hypoxia-inducible factor-1 (HIF-1) –> VEGF production

Question 6

Action of VEGF

Answer 6

1) increase endothelial permeability

2) MMP release to degrade basement membrane and extracellular matrix

Question 7

Key transcription factors

Answer 7

HIF-1 = induced by hypoxia
-induces angiogenesis

EGR-1 = induced by shear stress, mechanical injury, hypoxia
- regulator of cell cycle in vascular cells

Question 8

Key growth factors

Answer 8

VEGF - proliferation, migration, lumen formation; monocyte chemotaxis

FGF - endothelial/SMC proliferation, potentiates VEGF

TGF beta - in developing collateral arteries to stimulate arteriogenesis

TNF alpha - angiogenesis; activation and adhesion of monocytes; migration of hematopoietic cells to endothelium

GM-CSF - hematopoietic stem cells proliferation and differentiation; mobilize endothelial progenitor cells

HGF - augments arteriogenesis by enhancing endothelial cell function

Question 9

Key ECM protein involved with angiogenesis

Answer 9

Del-1

Question 10

Key chemokines

Answer 10

MCP-1 (CCR2)

ELR-containing CXC

Question 11

Key cell adhesion molecules

Answer 11

ICAM
VCAM-1
PECAM

Question 12

Fluid shear stress calculation

Answer 12

1) proportional to flow velocity

2) inversely proportional to radius cubed

Question 13

Increase fluid shear stress causes

Answer 13

1) NO synthase –> increase NO –> SMC relaxation –> vasodilation beyond occlusion
2) NO –> stimulate VEGF –> chemoattraction of leukocyte

Question 14

Circumferential wall stress activation

Answer 14

stimulate vascular SMC growth –> increase vessel thickness

Question 15

Pruning define

Answer 15

regression of smaller collaterals and persistence of fewer larger collaterals

regression cause by intimal proliferation to occlusion

Question 16

Opposing pathways of angiogenesis for regulation

Answer 16

VEGF - sprout

Notch signalling - stops sprout

Question 17

Interssusceptive angiogenesis definition

Answer 17

Formation of transcapillary tissue pillars that fuse to form new vessels

Question 18

Three basic mechanisms of intussusception angiogenesis

Answer 18

Intussusceptive microvascular growth = for tissue pillars
Arborization = develop vertical pillars
Intussuscpetive branching remodeling = vascular pruning and branching

Question 19

Benefit of intussusceptive growth

Answer 19

1) minimal endothelial proliferation
2) low vascular permeability
3 minimal tissue disruption

Question 20

Current gene/protein based therapy targets

Answer 20

1) VEGF - VEGF-PVD, RAVE
2) FGF - TAMARIS, TALISMAN
3) HGF (hepatocyte) - HGF-STAT
4) Del-1 - DELTA
5) HIF-1 - WALK

Question 21

Current cell-based therapies

Answer 21

1) Endothelial progenitor cells - START
2) bone marrow-derived cell - PROVASA, RESTORE-CLI
3) fully differentiated cells