Commentary: On the Pathophysiology of Coronary Heart Disease

This article highlights some important aspects of the pathophysiology of coronary artery disease, namely: • The distribution of lesions within the arterial tree at sites of low wall shear stress. • The potential role of low flow-mediated arterial dilatation at sites of low wall stress. • Low flow-mediated dilatation leads to low nitric oxide production by the arterial endothelium and consequent reduced protection against lesion formation. • Flow-mediated dilatation is reduced by high lumenal glucose concentration. • The role of the glycocalyx dysfunction in mediating flow-mediated dilatation and consequent reduced NO production by the arterial endothelium and cell adhesion. • Stenoses cause convective acceleration of blood velocity and a consequent increase in platelet shear stress. • Increased platelet shear stress activates platelets with release of serotonin. • Serotonin activates more platelet activation via the 5HT2A platelet receptor causing a positive feedback and thrombus growth. • Arterial thrombus growth is abolished by 5HT2A receptor antagonists, the key to improved treatment of the disease. • One 5HT2A receptor antagonist has been shown in humans to be safe and to cause no excess bleeding from wounds.