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Table 4 THE SPIRIT OF VASCULARIZATION (SEE FIGURE 6)

From: Vasa vasorum in plaque angiogenesis, metabolic syndrome, type 2 diabetes mellitus, and atheroscleropathy: a malignant transformation

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