Plaque Biology: Interesting Science or Pharmacological Treasure Trove?

Potentially unstable carotid plaque demonstrating thin fibrous cap and lipid rich core.

Unstable carotid plaque with evidence of ulceration, cap rupture and thrombus formation.

Histological sections of carotid plaques revealing features of plaque instability. H&E stained (a) carotid plaque with intraplaque haemorrhage (IPH), and EVG stained (b) plaque rupture (PR), (c) plaque cap thinning (PCT), and (D) plaque necrosis (PN). Magnification × 10.

The stages of plaque provide numerous potential targets for pharmacotherapy. Endothelial damage allows passage of inflammatory cells and LDL into the vessel intima; free radicals are responsible for oxidation of the deposited LDL; oxidized-LDL promotes cytokine and protease release from macrophages; proteases degrade the fibrous cap causing disruption; exposure of the thrombogenic core to the blood results in clot formation; local thrombotic and fibrinolytic activity determine the degree of thrombus progression or dissolution.

The level of MMP9 in carotid plaques from patients with thrombo-embolic symptoms within 4 weeks of surgery (group 4) was significantly higher the asymptomatic (group 1), and patients with symprtoms >6 months and 1–6 months before surgery (groups 2 and 3 respectively. MMP9 represents a potential target to prevent plaque destabilisation.

Immunostain demonstrating intense staining for MMP9 in the shoulder of an unstable carotid plaque, in an area of intense inflammatory infiltration.

Levels of control of MMP activity providing numerous potential targets for pharmacotherapy to alter the balance between proteolysis and matrix synthesis.