Translation of Pro-Angiogenic and Anti-Angiogenic Therapies into Clinical Use - Mechanical and Chemical Signaling in Angiogenesis - page 257

Excess
Angiogenesis:
Inflammation
Retinopathy
Nephropathy
Tumor formation

Optimal
Angiogenesis

Insufficient
Angiogenesis:
Deficient wound healing
Ulcer formation
Ischemia

Fig. 1 Implications of insufficient angiogenesis and excess angiogenesis for human disease

Table 1 The role of angiogenesis in the global burden of disease
Cause of death Annual deaths

worldwide, in
millions

%of
all
deaths

Role of angiogenesis in therapy

Coronary heart
disease

7.20 12.2 Improved angiogenesis may speed recovery

of cardiac muscle

Stroke and other
cerebrovascular
disease

5.71 9.7 Improved angiogenesis in the brain may

speed functional recovery

Chronic obstructive
pulmonary
disease

3.02 5.1 Improved angiogenesis of lung microvessels

may allow alveolar regeneration

Trachea, bronchus,
lung cancers

1.32 2.3 Blocking angiogenesis will halt growth of

malignant tumors

Diabetes mellitus 1.10 1.9 Improved angiogenesis will enable wound

healing; blocking angiogenesis will
prevent retinopathy

TOTAL 18.35 31.2

2 Angiogenic and Angiostatic Regulators

Angiogenesis is finely controlled, both spatially and temporally, via an intricate
system of molecular inducers and inhibitors. At least 50 different endogenous
molecules are known to regulate angiogenesis [ 6 ]. The most important pro-
angiogenic molecule is vascular endothelial growth factor (VEGF) [ 7 ], which
serves as a master regulator of physiological and pathological angiogenesis [ 8 ].
VEGF is produced and secreted by cells in response to hypoxia; under conditions
of low oxygen, a transcription factor known as hypoxia-inducible factor (HIF)