Table 1.

Therapeutic interventions that might improve vasculopathy.

InterventionMechanismEvidence
Sildenafil ↑ NO generation
 ↓ Platelet activation Human clinical trials46,74
 Case reports75,76  
Transfusion ↓ Hemolysis
 ↓ Inflammation Human clinical trials69,77,78  
Arginine ↑ NO generation
 ↓ Hemolysis
 ↓ Platelet activation
 ↓ Oxidative stress Human clinical trials36,38,79,81
 Sickle cell mouse studies37,39,82  
Glutamine ↓ Hemolysis
 ↓ Oxidative stress Human clinical trials83
 Endothelial culture experiments35  
Statins ↓ Oxidative stress
 ↑ NO generation Sickle cell mouse studies84  
Niacin ↑ ApoA-1
 ↑ HDL Human clinical trials85  
ApoA-1 mimetic (L-4F) ↓ Inflammation Sickle cell mouse studies50  
Hydroxyurea ↑ NO generation
 ↓ Hemolysis 2°
 ↑ Fetal Hb Human clinical trials86
 Endothelial culture experiments87  
InterventionMechanismEvidence
Sildenafil ↑ NO generation
 ↓ Platelet activation Human clinical trials46,74
 Case reports75,76  
Transfusion ↓ Hemolysis
 ↓ Inflammation Human clinical trials69,77,78  
Arginine ↑ NO generation
 ↓ Hemolysis
 ↓ Platelet activation
 ↓ Oxidative stress Human clinical trials36,38,79,81
 Sickle cell mouse studies37,39,82  
Glutamine ↓ Hemolysis
 ↓ Oxidative stress Human clinical trials83
 Endothelial culture experiments35  
Statins ↓ Oxidative stress
 ↑ NO generation Sickle cell mouse studies84  
Niacin ↑ ApoA-1
 ↑ HDL Human clinical trials85  
ApoA-1 mimetic (L-4F) ↓ Inflammation Sickle cell mouse studies50  
Hydroxyurea ↑ NO generation
 ↓ Hemolysis 2°
 ↑ Fetal Hb Human clinical trials86
 Endothelial culture experiments87  

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