Table 4 THE SPIRIT OF VASCULARIZATION (SEE FIGURE 6)
Process | Plaque Angiogenesis: Induced | Arteriogenesis: Impaired |
|---|---|---|
Substrate S | Capillary | Arterioles |
Promoter P | Hif-1 TACGTGCT and VEGF | Shear Stress SSRE: GAGACC |
Inducer I | Ischemia | Shear Stress |
Result R | More Capillaries | Larger remodeled Arteriole |
Inflammation I | (+) increases | (+) increases |
Time T | Hours → Days | Days → Weeks → Months |
PAI-1 Increased in Diabetes | (0) neutral Neutral effect: In Plaque. Ischemia "Shoulder" Macrophage and Hif-1 → VEGF override. Net effect neutral Plaque Angiogenesis remains induced: See Promoter and Inducer above. | (-) IMPAIRS Impairs Remodeling Collateralization due to negative effects on MMP activation and impaired ECM clearance for the remodeling collateralization mechanism. |
ROS Increased in Diabetes | (+) increases SYNERGISTIC (to the above) SPIRIT of vascularization | (-) IMPAIRS ? Neutral to Negative in Collateral Vessels: See Promoter and Inducer above. Shear Stress → eNOS upregulation and eNO may override the negative effect of redox stress. In the eNOS knockout model: Collateral formation was not impaired and the decreased flow could be restored with exogenous NO. This area of study needs further evaluation. |
Oxygen Content | HYPOXIA | NORMOXIA |