Cinaciguat restored the ability of aged rat livers to clear beta-amyloid and 'bad' cholesterol from the blood

An experimental drug restored the blood-filtering function of an aged liver

Scientists at the Keck School of Medicine of the University of Southern California tested whether age-related changes in the liver can be reversed with the experimental drug cinaciguat. The results of the study were published in the Journal of Biological Chemistry; Gazeta.Ru reports on the findings.

How the liver filter works and what changes with age

The researchers focused on the cells lining the sinusoids — specialized blood vessels of the liver. Normally, their surface is perforated with pores through which large molecules gain access to hepatocytes, the liver's main cells, which capture and process substances from the blood. With age, the number and size of the pores decrease, and such a filter works less effectively.

What the rat experiments showed

Old rats were given cinaciguat for two weeks and were compared with young animals and untreated old rats. After the course, the structure of the vascular cells became closer to that of young animals, and the liver's ability to remove substances from the bloodstream was restored. Beta-amyloid levels fell by roughly half, reaching values observed in young animals; the content of low-density lipoproteins — 'bad' cholesterol — also decreased.

The discovered mechanism and its significance for medicine

The effect turned out to be linked not only to the restoration of the pores: the scientists identified a signaling mechanism through which the cells of the vascular wall release the growth factor HB-EGF and help hepatocytes capture molecules more efficiently. With age, this connection weakens, and the drug made it possible to restore it. Since beta-amyloid is involved in the pathological processes of Alzheimer's disease, and excess LDL is linked to atherosclerosis, the liver is seen as a potential target for preventing age-related diseases. Earlier, as Gazeta.Ru notes, scientists had already linked cholesterol accumulation to impaired brain clearance.

Limitations and what remains unknown

The authors emphasize that lower levels in the blood do not yet prove protection of the brain or heart. The result has so far been obtained only in rats; whether the intervention prevents disease development and whether it would be safe for humans remains to be determined separately. The editorial board notes that the practical significance of the work is still limited to the preclinical stage: the publication contains no data on the drug's tolerability in humans or on clinical effects.