The Multifaceted Role of Platelets in Atherosclerosis and Ischemic Disease: Pathogenesis, Inflammation, and Therapeutic Opportunities

Figures

• 

  Figure 1. Mechanisms of platelet-mediated plaque formation and rupture. Increased adhesion molecules, CD36 and complement activation, increased production of chemokines and cytokines, increased immune cell recruitment contributing to chronic inflammation, and growth factors promoting angiogenesis contribute to plaque formation. Persistent inflammation and matrix degeneration results in plaque rupture, thrombus formation, and acute ischemic events. ↑ indicates increased expression and ↓ indicates decreased expression.

• 

  Figure 2. Plaque formation and rupture involving platelets. Activated platelets secrete platelet granules which in turn activate CD40-CD40L interaction. This increases immune cell recruitment in the vessel contributes to plaque formation. This also increases foam cell formation, vascular smooth muscle cell (VSMCs) proliferation, angiogenesis contributing to plaque progression. Persistent inflammation and immune cells, oxidative stress, and collagen degradation results in thin fibrous cap, the point of plaque rupture. ↑ indicates increased expression and ↓ indicates decreased expression.

• 

  Figure 3. Platelets and plaque rupture. Increased reactive oxygen species (ROS) contribute to endothelial dysfunction, oxidized low density lipoprotein (ox-LDL) accumulation, and immune cell recruitment leading to plaque progression. Further, increased matrix metalloproteinases (MMPs) contribute to collagen and elastin degradation resulting in thin fibrous cap. Persistent inflammation and the presence of necrotic core in the plaque results in plaque rupture. ↑ indicates increased expression.

• 

  Figure 4. Targeting platelets to attenuate plaque progression and rupture. Inhibiting platelet activation, the interaction between platelets and immune cells, and platelet aggregation are potential strategies to attenuate platelet progression and rupture thereby reducing acute ischemic events.