Self-cleaning of vessels prevents serious diseases

A biological mechanism has been discovered that cleans capillaries of microthrombs
LifeSciencesToday based on Nature News Blog:
New clot-clearing mechanism has implications for many big diseasesSome articles, which, as it seems, should have immediately attracted the attention of scientists, at first do not receive a proper response from the scientific community.

So it happened with the article by neurologist Jaime Grutzendler, MD, published in the journal Nature last May (Lam et al., Embolus extravasation is an alternative mechanism for cerebral microvascular recanalization). He described a previously unknown amazing biological mechanism by which the smallest capillaries of the brain are cleared of blood micro-clots and other "garbage", including fragments of cholesterol plaques and cell decay products.

Using modern microscopy techniques, Grootzendler and his group, then working at Northwestern University, Chicago, showed that the endothelial membrane of the capillary quickly covers blood clots. Then a gap forms in the capillary wall, through which the clot is removed from the vessel into the perivascular parenchyma. The membrane that has already formed around the breach immediately "seals" it, forming a new vessel wall. This prevents the formation of a hole in the capillary through which blood can leak, and local damage to the brain. Grootzendler calls this mechanism angiophagy. Scientists have shown that its effectiveness decreases with age.

Professor Grootzendler, who now works at Yale University, has just presented the continuation of this work at a meeting of the American Neurological Society (Society for Neuroscience), held this year in Washington, DC. He described how this mechanism functions throughout the body. Previously, it was assumed that it is present only in the capillaries of the brain.

This discovery has an impact on understanding the development of many diseases, for example, stroke, which is caused by blood clots blocking normal-sized cerebral blood vessels. Treatment with thrombolytic enzymes, such as tissue plasminogen activator (TAP), leads to the release of tiny fragments of blood clots into the bloodstream, which can eventually block microvessels. An ineffective angiophagy system cannot cope with microthrombs, which potentially explains why TAP therapy is sometimes unable to prevent brain damage.

A blood vessel in the mouse brain
First day: the inner lining of the blood vessel begins to spread (arrow)
a fragment of a cholesterol plaque (orange) is placed on the blocking lumen of the vessel.
Day three: The membrane surrounded cholesterol and created a pathway from the blood vessel (highlighted by arrows).
Day five: the blood clot has gone beyond the blood vessel, the lumen of which is now free (asterisk).

The same mechanism is involved in the development of dementia. Dementia is a consequence of vascular damage, or (in the case of classical Alzheimer's disease) amyloid pathology, or both at the same time. Often micro-strokes go unnoticed, as they are not accompanied by any symptoms. Ineffective angiophagy can accelerate the slow accumulation of damage around the smallest blocked capillaries to a destructive level. In addition, in Alzheimer's disease, amyloid peptides can be deposited not only around neurons, but also in blood vessels, thus complementing the damage caused by plaques, vascular damage, if the capillaries are unable to effectively clear them.

The new data obtained by Grootzendler show that ineffective angiophagy can also aggravate some peripheral diseases. These, for example, include temporary blindness, which develops as a result of the formation of blood clots in the blood vessels of the retina. The imperfection of this process can also have an impact on recovery after a myocardial infarction, the scientist believes.

 
Capillary ejecting thrombus
The shooting took place over five days (Photo: Jaime Grutzendler, Nature)

"I think that at first the article did not receive a wide response, because it turned out to be between areas of interest – "Alzheimer's disease" was really not its keyword," says Grootzendler. "But now invitations to speak at meetings of specialists are beginning to arrive little by little."

Now Grootzendler and his colleagues are trying to analyze the molecular components of angiophagy in the hope of finding targets for drugs.

Portal "Eternal youth" http://vechnayamolodost.ru
22.11.2011