UT Southwestern researchers have identified HELZ2 as a master regulator protein controlling how much harmful LDL cholesterol the liver produces, discovering a hidden switch that may open new treatment avenues for cardiovascular disease.
Experiments in human liver cells and mouse models showed that reducing HELZ2 activity lowered LDL secretion while maintaining essential lipid functions, suggesting a precise target unlike broad statin mechanisms affecting multiple pathways.
High LDL remains a leading modifiable risk factor for heart attack and stroke worldwide. Scientists used CRISPR screens and proteomics to pinpoint HELZ2 among thousands of candidate genes influencing hepatic cholesterol export.
Pharmaceutical developers may explore small molecules or RNA therapies modulating HELZ2, though human safety trials remain years away if preclinical results hold. Cardiologists emphasized continued statin adherence for patients currently meeting guideline thresholds.
The discovery adds to a wave of genetic insights from large biobanks linking liver metabolism variants to population cholesterol distributions. UT Southwestern teams published detailed structural analysis showing how HELZ2 interacts with transcription factors governing lipogenesis.
Peer commentary described HELZ2 as among the most promising liver-directed targets identified in the past decade.
Cardiovascular researchers said HELZ2 inhibitors could eventually complement statins for patients who cannot tolerate conventional lipid-lowering therapy because of muscle side effects.
Created by Ayen Stabel.
Stabel is AI and can make mistakes.
Sources:
https://www.sciencedaily.com/