Atherosclerosis from the slightest exposure to lead
(Vienna, 11 August 2010) Even in quantities well below the guidelines, lead damages health and is a serious risk factor for cardiovascular diseases. In their research, scientists at MedUni Vienna have also been able to describe for the first time the mechanism of action of the toxic metal on the human blood vessel walls.
Although cardiovascular diseases are the main cause of death worldwide (in Austria this is more than 50%) and many risk factors are described for these diseases, it is estimated that up to 25% of all cardiovascular diseases can still not be explained by known risk factors.
This is why the working group headed by Priv. Doz. Dr. David Bernhard at the Department of Surgery (Surgical Research Laboratories, Division of Heart Surgery) has been busy looking for new - so far unknown - risk factors for several years. One particular area of focus here has been metals. Dr. Iris Zeller, a researcher in Bernhard's group, has now been able to identify lead as one such risk factor in a human trial with young probands and also describe its mode of action.
According to these findings, lead levels in the blood serum which are much below the currently applicable guidelines already lead to changes in the blood vessel walls, which can be considered as preliminary stages of atherosclerosis. The underlying pathomechanism has also been described in detail: once lead has entered the bloodstream and is absorbed by endothelial cells (the first cell layer facing the bloodstream – "intima"), it activates the transcription factor Nrf2. Nrf2 activation by lead leads to the synthesis of interleukin-8 (IL-8), which is released by endothelial cells. In turn this IL-8 stimulates the migration of smooth muscle cells from a deeper layer ("media") of the blood vessel wall into the intima and makes them swell and change. This process is a key element in the development of atherosclerosis.
Although the harmful effect of lead has been known for a long time and the heavy metal is number two among the most dangerous substances, today it is still found in industrial waste gases (coal combustion), water pipes in older buildings, in varnishes, paints, etc., which is why its importance as a risk factor for cardiovascular diseases is being underlined. With such prevalence the study author Bernhard sees the high relevance of the findings: "Based on this study, exposure to lead should be reassessed as a risk factor for cardiovascular diseases even in small concentrations of the metal." The work was published in the internationally renowned specialist magazine ATVB (Arteriosclerosis, Thrombosis, and Vascular Biology).
» Picture: Shown here is a cross-section of a human artery which has been treated with lead in organ culture. The dark wavy line is the so-called "basal lamina", which separates the intima from the media. Smooth muscle cells are coloured red. Muscle cells between the basal lamina and the lower vessel edge (the vessel lumen is in the bottom part of the picture) were stimulated to migrate by lead. These cells are missing in untreated controls. Image width = approx. 150µm