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