An experimental drug restored important features of aging liver cells in older rats and reduced two substances in their blood linked to age-related disease, according to a study by researchers at the Keck School of Medicine of USC. After two weeks of treatment with cinaciguat, amyloid beta levels fell by about 50%, while LDL cholesterol dropped to levels observed in younger animals.
The study, published in the Journal of Biological Chemistry, examined liver sinusoidal endothelial cells, which line small blood vessels in the liver. These cells have tiny openings that help larger molecules reach neighboring liver cells, or hepatocytes, which process and remove substances from the body. With age, the openings can shrink or disappear, making the liver less effective at clearing some compounds from the blood.
In treated rats, cinaciguat restored the structure and function of these cells, including reopening their microscopic pores. The researchers also found that the drug activated a signaling pathway between the endothelial cells and hepatocytes. The pathway involves the enzyme soluble guanylate cyclase and the growth factor HB-EGF; signals from HB-EGF prompt hepatocytes to capture more amyloid beta and LDL from the bloodstream.
The LDL result surprised the researchers. They had expected the treatment to have little effect on LDL because the particles are small enough to pass through the bloodstream without relying on the liver cells’ pores. The finding suggested that cinaciguat may improve liver function through cell-to-cell communication as well as by restoring the physical filters.
Amyloid beta is associated with Alzheimer’s disease, while elevated LDL contributes to fatty deposits in arteries. However, the researchers cautioned that reducing amyloid beta in the blood does not establish that brain plaques will decline or that Alzheimer’s can be prevented. The results have so far been demonstrated only in rats, and further work is needed to determine whether the findings could lead to benefits in humans.
The team plans to continue studying whether cinaciguat’s effects on amyloid beta translate into measurable protection against Alzheimer’s disease. The study was led by Sam J. de Leve and Laurie D. DeLeve, alongside Xiangdong Wang, Helia Alavifard and Lily Dara, and received funding from the National Institutes of Health.
Sources: ScienceDaily.