Cardiology · 1 h ago
CTSA Inhibition Preserves LDL Receptors in Mice on High-Cholesterol Diets
A Nature study using mice and human cells identified a pathway linking dietary cholesterol to reduced liver LDL-receptor availability. Blocking the enzyme CTSA stabilized the receptors and lowered circulating LDL cholesterol in mice; the approach has not been tested for cholesterol lowering in humans.
- Dietary cholesterol activated a Ral–CTSA pathway in experiments.
- CTSA inhibition lowered LDL cholesterol in mice.
- Human cholesterol-lowering efficacy has not been tested.
- An unnamed inhibitor previously completed Phase 1 safety testing.
Researchers at the University of California San Diego used mouse experiments and human cells to investigate how a high-cholesterol diet can impair the liver’s clearance of LDL cholesterol. They identified a pathway in which dietary cholesterol activates the protein Ral, leading to cathepsin A (CTSA)-related depletion of LDL receptors on liver cells.
In mice, a small-molecule CTSA inhibitor stabilized LDL receptors and dramatically reduced circulating LDL cholesterol. The study describes a pathway distinct from those targeted by statins and PCSK9 inhibitors. The source provides no numerical effect size or sample size.
The findings are preclinical and do not establish that CTSA inhibition lowers cholesterol in people. A CTSA inhibitor developed for heart failure previously completed a Phase 1 safety trial, but the drug and trial results are not identified in the source. The researchers say it could be considered for a Phase 2 trial in high cholesterol; effectiveness in humans remains unknown. The work received partial NIH and American Diabetes Association funding.
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Nature (via ScienceDaily): Scientists discover a hidden driver of high cholesterol and a way to stop it ↗This is an automated AI-condensed summary that has not yet been reviewed by an editor. Always consult the full item at the original source.