What is Endothelial Dysfunction?  

What is the endothelium?

The endothelium is the inner lining of blood vessels, serving as an interface between them and the blood. It allows blood to flow smoothly within blood vessels. In 1980, scientists discovered that the endothelium is more than just a "Teflon like” lining – it’s actually the largest secreting organ in the body. The endothelium is a highly active organ which is involved in regulating homeostasis through numerous functions such as, blood pressure, inflammatory processes and coagulation. In 1998 Robert F Furchgott, Louis J Ignarro and Ferid Murad were awarded the Nobel Prize in medicine for this important discovery.

What is endothelial function?

The “normal” or healthy endothelium is involved in regulating homeostasis by secreting substances which protect vascular health. Chief among these substances is Nitric-Oxide – a two atom molecule, which is considered to be the hallmark of normal endothelial function. Together with several other substances, Nitric Oxide is involved in locally regulating processes such as

• Vascular tone
• Inflammation
• Coagulation
• Oxidation

If these processes are not strictly regulated, they can lead to impairment of vascular health, leading the way to subclinical atherosclerosis, all the way to cardiovascular disease.

Endothelial dysfunction

Endothelial Dysfunction is the result of the cumulative damage to the endothelium by cardiovascular disease risk factors such as genetics, smoking, Diabetes, high blood pressure and others. These risk factors cause the endothelium to malfunction: it secretes less of the protective molecules, such as Nitric-Oxide, and secretes substances which promote atherosclerotic plaque formation. Leading doctors at the Mayo Clinic proclaimed in a 2003 paper that “endothelial dysfunction may be regarded as the 'ultimate risk of the (cardiovascular) risk factors.'" It was identified as the missing link between cardiovascular risk factors and subclinical atherosclerosis. Endothelial dysfunction is now widely recognized in the medical community as the earliest clinically-detectable indication of heart disease. Unlike subclinical atherosclerosis, endothelial dysfunction, with proper treatment, is reversible.

How is endothelial dysfunction diagnosed?

Until recently, experts used various methods to assess endothelial function. These methods are categorized as either:

Invasive - which is painful and with a certain amount of risk; or

Noninvasive – which is user-dependent, meaning test results are prone to high variability between users, limiting its use to expert research sites.

To diagnose something as serious as endothelial dysfunction, a method is needed that can function with consistent accuracy, independently of the user. The Endo-PAT provides this combination of noninvasive, ease-of-use, independent of the user, while providing reliability. It has been scientifically validated in close to a hundred publications from clinical studies in top research centers (e.g., Framingham Heart Study, Harvard, Mayo Clinic and hundreds of others) around the world and is the method used to assess endothelial function in leading centers.   

In order to avoid confusion, please note that there are several noninvasive methodologies to assess cardiovascular disease risk. But all of them target subclinical atherosclerosis, which is when vascular health has already been compromised to a certain extent. This degeneration of the vasculature is irreversible. While endothelial dysfunction plays a key role throughout these phases of the atherosclerotic disease, it is not what these tests of cardiovascular risk measure.

Resources:

Bonetti OP, Lerman LO, Lerman A: Endothelial Dysfunction:       A Marker of Atherosclerotic Risk Arterioscler. Thromb. Vasc. Biol. 23, 168-175, 2003