# Cinaciguat Restores Liver Clearance and Halves Amyloid-Beta 40 in Aging Rats

- Published: 2026-11-06 19:08 UTC
- Section: Life & Health › Medicine
- Tags: cinaciguat liver clearance, amyloid beta 40 reduction, liver sinusoidal endothelial cells, pseudocapillarization aging, HB EGF paracrine signaling, LDL receptor surface expression
- URL: https://realtech.media/news/rt-f5fae619025954ffa11815fd_cinaciguat_restores_liver/

**A two-week treatment restored liver cell fenestration and paracrine signaling in aging rats, cutting circulating amyloid-beta 40 levels by half.**

![Cinaciguat Restores Liver Clearance and Halves Amyloid-Beta 40 in Aging Rats](https://sgzwpqqelzmajkcubgkl.supabase.co/storage/v1/object/public/rt-media/2026/11/e760cdf831e91a54.webp)
*ScienceAlert*

Researchers at the University of Southern California have restored liver clearance functions and reduced circulating levels of amyloid-beta 40 by half in two-year-old rats using the experimental compound cinaciguat, according to a study published in the Journal of Biological Chemistry [1]. The two-week regimen returned the concentration of this protein fragment, which is linked to Alzheimer's disease, to levels typically observed in four-month-old animals.

In a healthy liver, blood-borne macromolecules move into the space of Disse through fenestrations in liver sinusoidal endothelial cells (LSECs). During aging, these pores close in a process known as pseudocapillarization, blocking large triglyceride-rich lipoproteins that carry most circulating amyloid-beta. Daily administration of cinaciguat, an activator of soluble guanylate cyclase, reversed this degradation and reopened the endothelial fenestrations [1]. Unexpectedly, the treatment also lowered levels of low-density lipoprotein (LDL), a smaller particle that usually crosses the endothelial barrier regardless of fenestration loss.

## Endothelial signaling mechanisms

To understand the reduction in LDL, investigators evaluated intercellular communication between LSECs and hepatocytes. Primary hepatocytes cultured alone showed minimal clearance of amyloid-beta 40 or LDL, but medium conditioned by young rat LSECs preserved their uptake capacity [1]. In contrast, medium from untreated aged LSECs failed to stimulate clearance unless the donor animals had received cinaciguat.

## Growth factor secretion

The team identified heparin-binding epidermal growth factor-like growth factor (HB-EGF) as the primary paracrine mediator of this interaction [1]. While aged LSECs continued to synthesize HB-EGF precursors, they failed to secrete the active soluble protein. Cinaciguat treatment restored HB-EGF secretion, which in turn reinstated surface expression of the low-density lipoprotein receptor (LDLR) and low-density lipoprotein receptor-related protein-1 (LRP1) on hepatocytes [1]. The researchers noted that further studies are required to determine whether enhanced hepatic clearance influences amyloid accumulation in the brain.

## Sources

1. [Journal of Biological Chemistry](https://doi.org/10.1016/j.jbc.2026.113608)
2. [ScienceAlert](https://www.sciencealert.com/drug-restores-liver-function-in-aging-rats-and-halves-levels-of-an-alzheimers-linked-protein)

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Source: RealTech, realtech.media — https://realtech.media/news/rt-f5fae619025954ffa11815fd_cinaciguat_restores_liver/