2014 Williams Harvey Lecture: importance of coronary vasomotion abnormalities-from bench to bedside

Area of Science:

• Cardiovascular Medicine
• Molecular Biology
• Physiology

Background:

• Coronary vasomotion abnormalities are central to ischemic heart disease pathogenesis.
• Endothelial vasodilator functions vary by vessel size, with nitric oxide (NO) dominant in conduit arteries and endothelium-derived hyperpolarizing factor (EDHF) in resistance arteries.
• Endothelium-derived hydrogen peroxide is a key EDHF in resistance arteries.

Discussion:

• Coronary artery spasm, driven by vascular smooth muscle cell (VSMC) hypercontraction via Rho-kinase activation, is a major factor in ischemic heart disease.
• The Rho-kinase pathway is implicated in various cardiovascular diseases, with inhibitors in development.
• Deletion of all three NO synthases reveals the importance of both NO and EDHF in cardiovascular and metabolic health.

Key Insights:

• Heterogeneity in endothelial vasodilator functions (NO vs. EDHF) based on vessel size.
• Rho-kinase pathway's critical role in VSMC contraction and coronary artery spasm.
• The combined importance of NO and EDHF in maintaining cardiovascular and metabolic homeostasis.

Outlook:

• Ongoing international registry studies aim to further elucidate vasospastic angina.
• Coronary vasomotion abnormalities represent a significant therapeutic target in cardiovascular medicine.
• Development of novel Rho-kinase inhibitors holds promise for treating cardiovascular diseases.