Monday, November 7, 2011

Probe detects early form of dangerous blood cloths

A new molecular probe developed by Massachusetts General Hospital seems able to detect changes in walls of arteries that reveal early deposits of substance that could later break loose and turn into a blood cloth. These, often fatty, deposits also cause the vascular wall to become narrow, thereby restraining blood flow. The newly developed probe is able to travel through the arteries, and because it has a fluorescent label attached to it, will light up the places in our vascular network where a possible dangerous placque is developing.

For the development of the probe, the scientists took a small molecule that is able to recognize other molecules that are often involved with formation of the placques found in atherosclerosis, a disease where the vascular walls get covered by fatty deposits, impairing the function of the blood vessel. This is especially problematic in the largest arteries of our vascular network, which have a high elasticity to deal with the highly pressurized blood that is pumped into our system by the heart. A protein called fibrin is important in forming blood cloths, by deploying a threadlike structure that functions as a net, to "capture" other blood proteins. This is, in an early stage, detected by the probe. It also recognizes cathepsin B, which is found in the most dangerous of placques. By this, the detector is able to distinguish between severity of the deposits that are being found on vascular walls. It also shows whether the placques found have a big risk of detaching from the vascular wall, and form a dangerous blood cloth.

Existing probes make use of cameras, so doctors have to physically observe the placques in order to determine the risk of developing possibly lethal blood cloths and assess the disturbed blood flow by the thickened vascular walls. However, when the deposits are visible, the disease process is not in an early phase anymore. The molecular probe is better suited to detect risks on developing full-blown atherosclerosis early, so the patient can start changing his or her lifestyle, to prevent complications in a later phase.

Atherosclerosis, which is marked by deposit of fatty substance on the vascular wall, is highly prevalent in the western world, as it is caused by fatty foods and high cholesterol. Over time, arterial walls can lose their elastic and muscular strength because fatty substances accumulate and form a placque. This poses several risks. A complicated placque can rupture, causing internal bleeding which can lead to death. In addition, thickening of the vascular wall can cause hypoxia; a lack of oxygen. Placques can also detach from the vascular wall and start travelling through the blood. This is known as an embolism, and it is extremely dangerous. A solid placque could end up in the brain, causing an infarct.
From top to bottom, the different stages in placque formation.
Detecting specific molecules is nothing new. It is already being deployed for countless of therapies in the medical world. A molecular probe for the detection of possibly hazardous cloths, however, did not yet exist. Detection of specific molecules is performed with molecules that are derived from our body's own immune system. Antibodies, produced by white blood cells called B lymphocytes, only recognize a very specific structure, and billions of different versions can be created by our body, to ensure that we can recognize every single foreign molecule that is out there, including pathogens such as bacteria and viruses. Antibody-based therapy is also deployed in cancer, for example. By attaching a cytotoxical compound to an antibody, a lethal dose of 'cell poison' can be delivered specifically to the cells that we want to kill. A lot of these so-called 'magic bullets' are in clinical trials. 

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