Animal studies target atherosclerosis via fat cells and blood flow

At bends and branches in arteries, disturbed blood flow can activate inflammatory pathways. Two studies from Marshall University and Yale report that blocking different signals reduced atherosclerotic plaque in animal models, opening two research paths toward treating atherosclerosis.

Yale’s team, led by associate research scientist Divyesh Joshi and principal investigator Martin Schwartz, focused on PRC2 — a protein complex that inhibits gene expression — in vascular endothelial cells, the cells lining arteries. Disturbed flow at curves and branches was associated with higher activity of genes linked to PRC2 and suppression of anti-inflammatory genes. In cells treated with tazemetostat, a drug that inhibits PRC2, inflammatory signals fell; in animal models, the drug slowed plaque growth and reduced vulnerable plaque.

That matters because a plaque is often quiet until its fibrous cap weakens and ruptures, forming a blood clot that can cause a heart attack or stroke. Schwartz’s team says inhibiting PRC2 boosted protective pathways and shifted unstable plaque toward a more stable form. But tazemetostat comes with a major caveat: its manufacturers withdrew it from the market after emerging evidence that patients taking it faced a slightly increased risk of secondary cancers. The researchers say other PRC2-inhibiting drugs could prove useful.

At Marshall University Joan C. Edwards School of Medicine, Bruno Goncalves and Komal Sodhi took a different route, inside adipocytes — fat cells. Using male and female Apoe knockout mice fed a Western diet, the researchers blocked Na/K-ATPase (NKA) signaling specifically in those cells. Plaque formation fell, as did inflammation in blood vessels; the study also examined oxidative stress and metabolic dysfunction, linking fat-tissue signaling to vascular disease.

Concretely, the findings give researchers two preclinical routes to test: change how fat cells signal, or restore the artery’s anti-inflammatory programs by inhibiting PRC2. They do not yet amount to a treatment for patients: the Marshall result is in mice, while Yale’s evidence combines experiments in human endothelial cells with animal models. Neither report describes a human treatment or clinical outcome.