ALBA Synchrotron’s X-ray microscope enabled researchers to obtain 3D images of cells full of tiny cholesterol crystals, which may yield clues to how plaques form in blood vessels
Barcelona's Synchrotron Park; inset: Neta Varsano
PhD student Neta Varsano from the Weizmann Institute of Science recently examined samples of immune cells called macrophages at the MISTRAL microscope – a part of the ALBA synchrotron in Barcelona, Spain, headed by Dr. Eva Pereiro. This high-powered x-ray microscope – one of only three in the world — enables scientists to obtain 3-D images of the whole cell, without the need to slice it in thin layers. In other words, the images are obtained in very life-like conditions. The macrophages enriched with cholesterol were prepared and characterized by advanced microscopy techniques by the Israeli team, including Dr. Tali Dadosh.
Macrophages that carry cholesterol in the bloodstream have been implicated in inflammation and the subsequent formation of harmful deposits known as atheroma plaques. These macrophages first excrete the cholesterol crystals and then leave them behind on the blood vessel walls when the cells die. As more and more cholesterol is laid down in these plaques, blood vessels become blocked and atherosclerosis results.
When there is a glut of cholesterol, the macrophages swell, becoming lipid-filled “foam cells”
Although the process of plaque formation has been well studied, it is still not clear how the cholesterol crystals form within the immune cells. The Weizmann Institute of Science team is led by Profs. Lia Addadi and Leslie Leizerowitz, in collaboration with Dr. Howard Kruth of the Laboratory of Experimental Atherosclerosis in NIH. The scientists explain that the immune system responds to an excess of the LDL lipoproteins – proteins that carry cholesterol – in the bloodstream. They appear, initially, to go to the artery walls where the LDL is arrested in order to clean up the excess cholesterol. But when there is a glut of cholesterol, the macrophages swell, becoming lipid-filled “foam cells” that eventually die, leaving cholesterol crystals and other debris to form plaques on the blood vessel lining.
The results of the ALBA experiment are giving the researchers insight into what happens inside the macrophages between the time they ingest the cholesterol and the time that cholesterol is laid down, crystallized, in atheroma plaques.
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