Journal of Medical & Surgical Pathology
Open Access

Abstract

Commentary: On the Pathophysiology of Coronary Heart Disease

Mark I.M. Noble

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.