|
| Molecular target | Downstream effect | Statin effect | References |
|
| OATP2B1 | Drug entry into the platelet | Atorvastatin (act)
Simvastatin (act)
Pravastatin (act) | [9] |
|
| Phospholipase A2-thromboxane A2 (TXA2), MAP kinase | ↓ Ca inside the platelets
↓ COX-1 activity
↓ quantity and activity of prostaglandins | Pravastatin (inact)
Simvastatin (act)
Atorvastatin (act)
Rosuvastatin (act) | [13]
[14]
[15]
[16]
[17] |
|
| eNOS (NO synthase) | ↑ NO
↓ Ca inside the platelets | Pravastatin (act) | [36] |
|
| HO-1 | Antioxidant effect | Rosuvastatin (act) | [24] |
|
| CD36, LOX1 (ox-LDL receptors) | Modulation of the quantity and quality of these two receptors, both strong platelet activators | Atorvastatin (act)
Pravastatin (act)
Simvastatin (act)
Rosuvastatin (act) | [26]
[27]
[28]
[29]
[17] |
|
| NADPH-NOX-2 | ↓ isoprostanes, family of chemically stable eicosanoids that contribute to propagation of platelet activation via upregulation of the glycoprotein IIb/IIIa (GpIIb/IIIa)
↓ ROS
↑ NO
↓ PKC phosphorylation and p47phox translocation | Rosuvastatin (act)
Atorvastatin (act) | [30]
[23]
[31]
[32]
[16]
[33]
[20] |
|
| CD40L | ↓ proinflammatory and prothrombotic activity, including increased expression of matrix metalloproteinases and chemokines | Atorvastatin (act) | [34] |
|
| PAR-1 (protease-activated receptor-1) | ↓ PAR-1, responsible for attracting thrombin to the platelet surface, serving as a modulator between platelet activation and thrombin formation and its shredding from the cell surface | Atorvastatin (act)
Fluvastatin (act)
Lovastatin (act)
Pravastatin (act)
Rosuvastatin (act)
Simvastatin (act) | [37] |
|
| Mitochondrial respiration enzymes (complex I-linked respiration) | Unknown | Simvastatin (act) | [38] |
|
| TF, TF-PCA, membrane cholesterol content | GPIba-mediated activation of platelet TF triggers the generation of FXa
Platelet TF has the capacity to initiate the clotting process
Membrane cholesterol content plays important roles in platelet activation and calcium signaling | Rosuvastatin (act)
Atorvastatin (inact) | [39] |
|
| CD62 (P-selectin) | ↓ P-selectin regulates adhesion of activated platelets to neutrophils and monocytes and also to the endothelium and stabilizes the initial GPIIb/IIIa-fibrinogen interaction, allowing the formation of large, stable platelet aggregates | Atorvastatin (inact) | [40] |
|
| DKK-1 | ↓ mevalonate pathway | Atorvastatin (act) | [42] |
|
| PPAR alfa and PPAR gamma | ↓ AKT
↑ cAMP
↓ ERK
↓ p38
↓ MAPK
↓ Ca cytosol
↓ protein kinase C | Simvastatin (act)
Atorvastatin (act) | [18]
[11] |
|
| Circulating microparticles (cMPS) | TF (tissue factor)
P-selectin
CD14
GPIIIa | Atorvastatin (inact)
Pravastatin (inact)
Simvastatin (inact)
Rosuvastatin (inact)
Lovastatin(inact) | [46]
[43]
[44]
[45] |
|
| GRP78 | Chaperon protein | Rosuvastatin (act) | [47] |
| miRNA | miR-155 expression through interfering with the mevalonate-geranylgeranyl-pyrophosphate-RhoA signaling pathway and then increasing endothelial NO synthase expression and endothelium-dependent vasodilation | Atorvastatin (act)
Simvastatin (act) | [48] |
|
| BCL2-caspase, TNF | ↑ apoptosis | Lovastatin (act) | [2] |
|
