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Table 1 Possible therapeutic impact of selected anti-platelet agents in systemic vasculitides and systemic sclerosis

From: Parietal and intravascular innate mechanisms of vascular inflammation

Drug

Mechanism of action

Possible applications

Aspirin

• COX inhibition

• Inhibition of vessel remodeling in large vessel vasculitides (conflicting results in clinical trials)

 

â—‹ TXA2 inhibition

â—‹ Inhibition of vessel remodeling and vasoconstriction (possibly in synergy with PGI2 analogues) in SSc (limited data supporting modest efficacy in clinical settings)

 

â—‹ Inhibition of EGFR signaling and reduction of VEGF, MMP and IL-12 production

 
 

• Non-COX-dependent inhibition of leukocyte infiltration of the vessel walls

 

Dipyridamole

• Adenosine reuptake inhibition and cyclic nucleotide phosphodiesterase inhibition

• Inhibition of PDGF-mediated vessel remodeling and platelet-leukocyte interactions in giant cell arteritis

 

• Interference with platelet–leukocyte aggregation

• Vasodilation and interference with vessel and tissue remodeling in SSc (promising results from preclinical studies, but nonconclusive results in clinical studies)

 

• Inhibition of PDGF secretion from platelets

 

Vorapaxar, atopaxar

• Thrombin receptor (PAR-1) antagonism

• Prevention of thrombotic events due to enhanced endothelial and platelet activation in vasculitides with frequent thrombosis (for example, Buerger’s disease, Behçet’s disease or AAV)

 

• Inhibition of platelet activation

 
 

• Inhibition of endothelial activation

 

Sarpogrelate

• Serotinin 5HT2A,B receptor antagonism: impaired loading and release of serotonin by platelets

• Inhibition of fibrosis and vessel remodeling and reduced pulmonary hypertension in SSc (two small Japanese studies report apparent benefits in the control of skin ulcers and improvement in right ventricular ejection fraction, CO diffusion and pulmonary arterial pressure)

 

â—‹ Inhibition of serotonin-induced vasoconstriction

• Inhibition of vessel remodeling and pulmonary hypertension in Behcet’s disease, Takayasu’s arteritis and other inflammatory conditions

 

â—‹ Inhibition of serotonin-mediated endothelial toxicity

 
 

â—‹ Inhibition of serotonin-induced platelet activation

 
 

â—‹ Inhibition of serotonin-induced fibrosis

 
  1. AAV, anti-neutrophil cytoplasmic antibody-associated vasculitides; CO, carbon monoxide; COX, cyclooxygenase, EGFR, epidermal growth factor receptor; IL, interleukin; MMP, matrix metalloproteinases; PAR-1, protease activated receptor-1; PDGF, platelet-derived growth factor; SSc, systemic sclerosis; TXA2, thromboxane A2; VEGF, vascular endothelial growth factor.