Cinaciguat halved amyloid beta in old rats — ScienceDaily
Researchers at the Keck School of Medicine of the University of Southern California found that the experimental drug cinaciguat restored the function of specialized liver cells in old rats. After two weeks of treatment, the concentration of amyloid beta in the animals’ blood decreased by about 50% and reached the level seen in young rats. The level of low-density lipoprotein LDL, often called “bad” cholesterol, also declined to the levels of young animals.
ScienceDaily reports on the results, published in the Journal of Biological Chemistry. The researchers studied liver sinusoidal endothelial cells, or LSECs. They line small blood vessels in the organ and have microscopic pores through which large molecules can reach hepatocytes involved in blood purification.
Restoring liver filters
With age, pores in LSECs narrow or disappear, making it more difficult for some molecules to reach hepatocytes for subsequent removal from the body. The scientists suggested that this process may explain the reduced ability of the liver to clear amyloid beta from the blood in old animals. After treatment with cinaciguat, the structure and functions of LSECs were restored; in particular, the drug helped reopen microscopic pores.
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LDL was initially measured as a comparative indicator: its particles are small enough to leave the bloodstream without passing through LSEC pores. Therefore, the scientists did not expect the drug to have a significant effect on its concentration. However, LDL levels in old rats treated with cinaciguat also decreased to the values seen in young animals.
Signal between cells
Further analysis showed that cinaciguat activates the enzyme soluble guanylate cyclase in LSECs. In response, these cells release the growth factor HB-EGF, which transmits a signal to neighboring hepatocytes. The hepatocytes then alter their surface so that they can capture more LDL and amyloid beta from the blood.
The authors emphasize that the results were obtained only in rats. A reduction in the concentration of amyloid beta in the blood does not automatically mean a reduction in amyloid plaques in the brain or prevention of Alzheimer’s disease. The researchers plan to continue experiments in rats to determine whether this effect influences protection against the disease.
