The Endothelium in Diabetes
It is well known that cardiovascular disease (CVD) is a major cause of morbidity and mortality for individuals with diabetes. The common conditions that coexist with type 2 diabetes, such as hypertension and dyslipidemia, are clear risk factors for CVD. There have been a number of studies that have shown the efficacy of controlling individual cardiovascular risk factors in preventing or slowing CVD.
Researchers are studying the role of endothelial dysfunction as a possible mechanism by which Type 2 diabetes increases the risk of CVD.
The endothelium, a single layer of cells that lines the heart and blood vessels, is responsible for maintaining vascular homeostasis. Endothelial cells cover a surface area larger than the skin, and form a barrier between a blood vessel’s lumen and its smooth muscle lining. The endothelium is metabolically active, and releases nitric oxide and other vasoactive substances that influence thrombosis, fibrinolysis, antiproliferation, and the inflammatory response.
Researchers have been interested in the vascular endothelium and its role in the development of heart disease and diabetic retinopathy. Endothelial dysfunction, a condition in which the blood vessels are unable to dilate fully when needed, is thought to be one the earliest signs of atherosclerosis. Research indicates that endothelial dysfunction tends to develop before the blood vessel walls start to thicken and before atherosclerotic plaques begin to appear on them. The dysfunction of the endothelium may cause atherosclerosis by promoting stiffening of the blood vessels, adhesion of platelets to the inner walls of blood vessels, inflammation, and blood clotting.
The health of the endothelium can be assesses either invasively, or by noninvasive methods. One invasive method is a quantitative coronary angiography, which involves injecting acetylcholine into the vasculature. If the endothelium is healthy, the vessels relax. Endothelial dysfunction is indicated by vessel constriction. Various noninvasive tests include Doppler echocardiogram, positron emission tomography and magnetic resonance imaging. The flow-mediated dilation of the brachial artery is a simple test that is conducted at the Vascular Clinical and Translational Center (VCTRC) at the University of Pittsburgh. The procedure includes placement of a blood pressure cuff on a patient’s arm, inflating the cuff above the systolic pressure for five minutes, and releasing the cuff, and using Doppler flow to look at the reactive hyperemia that occurs. If blood vessels dilate as the blood rushes back, this indicates that the endothelium is healthy. If the endothelium is dysfunctional, the blood vessels do not respond.
In addition to promotion of a healthy lifestyle, by the reduction of modifiable risk factors, research is being conducted on improving the health of the endothelium, and ultimately, reducing the risk of heart disease. One area of study is the development of drugs (anti-VEGFs) that block the receptors within the endothelium that tend to promote the growth of new blood vessels. The receptors on the endothelial cells tend to promote angiogenesis, with the help of growth factors such as vascular endothelial growth factor (VEGF). These cells can adversely affect diabetic retinopathy by promoting the development of abnormal new blood vessels in the retina. Diabetic retinopathy may be stopped or delayed with the use of drugs that block the action of VEGF.
A healthy endothelium is necessary to maintain vascular homeostasis and to reduce the risk of cardiovascular disease. It is likely that the endothelium’s influence on the cardiovascular system will become more important in clinical medicine. With increased understanding of the endothelium’s crucial role in disease and health, the diabetes educator can help people with diabetes adopt healthy lifestyles.
Louise DeRiso, MSN, CRNP, CDE
Nurse Manager, Vascular CTRC
University of Pittsburgh