Fig. 6

Scheme depicting the role of Shh signaling in stimulated platelets. Short-range autocrine/juxtacrine/paracrine signaling by Shh amplifies thrombin-induced platelet activation responses through non-canonical activation of RhoA and AMP-activated protein kinase (AMPK) in a feed-froward loop akin to those involving ADP and TxA2. Shh antagonists (cyclopamine/vismodegib), cyclooxygenase inhibitors (aspirin), and P2Y12 antagonists (clopidogrel) target these feed-forward loops to limit platelet activity