Fundamentals of Endothelial Function for the Clinical Cardiologist

Case presentation 1: Mr Gundry is a 42-year-old construction worker who has had type II diabetes mellitus for the past 6 years. He has no other vascular risk factors and is currently asymptomatic. Is this patient at risk of developing endothelial dysfunction?Case presentation 2: Mr Sinha is a 64-year-old man who presents to your office for symptomatic intermittent claudication. Past medical history is unremarkable except for the presence of multiple vascular risk factors (smoking, hypertension, dyslipidemia, and obesity). How do vascular risk factors cause endothelial dysfunction? Is endothelial dysfunction treatable?A survey of medical history will reveal that major breakthroughs are often a result of simple and at times unexpected observations. Indeed, the era of endothelial biology was brought to the forefront through a simple pharmacological experiment conducted approximately 2 decades ago in Dr Furchgott’s laboratory.1 In this landmark study, the authors described the essential role of the endothelium in mediating the vasodilatory actions of acetylcholine, now known to be dependent on the release of nitric oxide (NO) from the endothelium. No one could have predicted that this observation would have the gargantuan impact on vascular biology that is evident today. Endothelial dysfunction now is implicated in the pathogenesis and clinical course of the majority of cardiovascular diseases. The purpose of this “Clinical Cardiology: Physician Update” is to provide the busy cardiovascular specialist with some of the fundamental principles of endothelial function as they relate to cardiovascular health and disease.The endothelium is a single-cell lining covering the internal surface of blood vessels, cardiac valves, and numerous body cavities. The strategic location of the endothelium allows it to “sense” changes in hemodynamic forces and blood-borne signals and “respond” by releasing vasoactive substances. A critical balance between endothelium-derived relaxing and contracting factors maintains vascular homeostasis. When this balance is …