Heart attack treatment: liposomes call for help
Synthetic "dead men" treat the heart after a heart attack
text: Alla Solodova, Infox.ru
Cardiologists are able to restore the heart after a "rupture" – myocardial infarction (MI). To save the patient's life, cardiologists need, firstly, to minimize the area of myocardial damage, and secondly, to stimulate the restoration (replacement) of damaged tissue.
The eaters are dismantling the rubbleImmediately after MI, local and external immune cells-eaters (macrophages) in response to necrotic biochemical signals are activated – cells accumulate in the area of the affected tissue.
Macrophages begin to "sort out the rubble": dispose of dead cells and repair a damaged heart. At the biochemical level, macrophages control the formation of new capillaries and the healing of heart wounds. However, the positive effect of immune cells does not manifest itself immediately. This happens only after another subpopulation of devouring cells stops causing inflammation. That is, first macrophages cause inflammation, then lick wounds. The degree of heart damage depends on the duration and scale of action of macrophages-inflammations.
Deceive the immune systemResearchers from Israeli universities led by Tamar Harel-Adar from Ben-Gurion University of the Negev have proposed a fundamentally new strategy for therapeutic control of infarction: in order to stop the lesion, it is necessary to attract the attention of a subpopulation of macrophages-restorers, giving signals about mass cell apoptosis and incipient necrosis.
That is, scientists decided to deceive the immune system by exaggerating the scale of the disaster in the "molecular biochemical report". Theoretically, the deceived immune system should throw anti-inflammatory cytokines (TGFß, IL-10) into the affected area and activate the necessary receptors (CD206). At least, this is what happens in the biological system without outside interference: when macrophages recognize a dead cell by a specific molecule (ligand) on its surface, they stop secreting inflammatory compounds and move from destruction to creation.
For the experiment, scientists synthesized small bubbles (liposomes), on the surface of which there is a "cell death signal" – phosphatidylserine (FS, in the figure – PS). The size of liposomes (1.2±0.3 microns) corresponded to the absorbing abilities of macrophages: phosphatidylserine receptors (PSR in the figure) effectively bound to FS, and the liposome "did not become in the middle of the throat" of the devouring cell. The therapeutic viability of the deception strategy was tested by scientists in in vitro and in vivo experiments. Biologists compared the obtained results with the action of liposomes-pacifiers and with inactivity.
Immunity believedScientists were convinced of the viability of FS-liposomes, after which they moved on to animal experiments.
The researchers provoked myocardial infarction in mice and treated the animals with direct injections of FS-liposomes into the affected area. In this experiment, Tamar Harel-Adar and colleagues did not restore the heart, but carried out a qualitative and quantitative analysis of macrophages. As expected, after the injection, the ratio of inflammatory and regenerating macrophages changed in favor of the latter. Moreover, under the influence of FS-liposomes, macrophages began to synthesize anti-inflammatory cytokines on the third day. Without FS-liposomes, this process started a day later.
In the next experiment, the scientists successfully treated laboratory rats: FS liposomes were injected into the femoral vein 48 hours after myocardial infarction. On the fourth day of experimental therapy, macrophages have already begun to restore the heart. The hearts of the animals from the control group continued to ache and slowly die.
"Histological, cytological and biochemical analyses confirm the therapeutic efficacy of PS-liposomes," write the authors of the article Modulating of cardiac macrophages by phosphatidylserine-presenting liposomes improves infarct repair, published in PNAS. Scientists also explain that it was previously proposed to treat hearts with dead cells, which, according to the same principle, activated the creative functions of immunity. However, this approach has been associated with a high risk of autoimmune diseases. Synthetic "dead men" control macrophages locally and, apparently, do not threaten the health of other tissues and organs.
For the practical application of the proposed strategy, it is necessary to conduct a number of more studies.
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19.01.2011