|
Atomic absorption spectroscopy was key to research that really gets to the heart of the problem of arterial plaques. Xi-Ming Yuan of Linköping University, Sweden, and colleagues there and at the University of Louisville, Kentucky, have identified the toxic components of arterial plaques seen in atherosclerosis, that kill the white blood cells that would otherwise help the body break down the plaques. The researchers say that the insoluble material within advanced atherosclerotic plaques contains calcium and iron and despite its fluorescent nature, closely resembles hydroxyapatite and dentin, the minerals of bone and teeth. Previously, Yuan and his colleagues suggested that the plaques, or more formally atheroma lesions, represent a "death zone" in the artery. This region contains toxic materials that can prevent invading white blood cells, or macrophages, from carrying out their normal function and even kill them. The result is that atheroma lesions are not removed and ultimately lead to heart problems and failure. These plaques can break apart at any stage in a person's life, whether they are otherwise fit or not, leading to cardiac arrest and death, this seems to occur most commonly in middle age. The researchers have now extracted the insoluble material present in atheroma lesions and used atomic absorption, Fourier transform infrared, and Raman spectroscopies to analyse its constituents. They have also shown that these isolates - so-called non-fractionated "gruel" and insoluble, ceroid-like, material - are cytotoxic to macrophages. The gruel component contains abundant carbonyl compounds and aldehydes and was shown to be more toxic than the ceroid-like fraction. The team incubated the crude gruel and ceroid with various compounds, such as borohydrides, to mop up the iron, calcium, and reactive aldehyde compounds and fount that they could effectively reduce cytotoxicity, suggesting that it is these components that are responsible for the cytotoxicity. Atheroma lesions are notoriously persistent once their formation has been initiated. This is in stark contrast to other lesions in the body that are usually acted on by macrophages and other inflammatory cells to remove or heal damaged tissue. Yuan and his colleagues discovery of the death zone in arterial plaques and their analysis of its constituents offer one explanation of why this is the case. It also suggests a novel approach to treating atherosclerosis using compounds that can chelate the cytotoxic components of the plaque and allow it to be broken down by macrophages. More detailed studies will be needed before such a therapeutic approach could be followed. "Atherosclerosis includes the processes of both atherosis and sclerosis of arterial walls," Yuan told SpectroscopyNOW.com, "In general, we know much more of atherosis than sclerosis. This study may offer useful approaches to further investigate both process in atherogenesis." The researchers have also recently developed a promising approach to investigating the pathophysiological effects of oxysterols, a group of compounds the activity of which is closely related to the effects of the death zone (See Free Radic Biol Med, 2006, 41, 902-910 and related commentary in Free Radic Biol Med, 2006, 41, 872-873). Related links:
|
Death zone keeps arteries clogged |
