ATAC-seq revealed that simvastatin-treated cells had closed chromatin structures that reduced the expression of genes that cause the endothelial-to-mesenchymal transition. Working backward, the researchers found that simvastatin prevents a protein known as YAP from entering the nucleus and opening chromatin.

The YAP protein is known to play important roles in development, such as regulating the size of our organs, but also has been implicated in the abnormal cell growth seen in cancer.

To see the drug in context, the researchers tested simvastatin on diabetic mice. Diabetes causes subtle changes to blood vessels that mimic the damage commonly seen in people who are prescribed statins older patients who do not have a cardiovascular condition, Liu said.

They found that after eight weeks on simvastatin, the diabetic mice had significantly improved vascular function, with arteries that more easily relaxed and contracted.

If we can understand the mechanism, we can fine-tune this drug to be more specific to rescuing vascular function, Liu said.

The findings also provide a more detailed picture of the vascular disease process, which could help doctors identify and treat early signs of vascular damage.

Ive been taking statins for the past 10 years to keep my cholesterol down. I also knew it has good vascular effects. I just didnt know how it does it, said Wu, the Simon H. Stertzer, MD, Professor who is also the director of the Stanford Cardiovascular Institute. This study explains how.

Researchers from the University of North Texas and the Ohio State University College of Medicine contributed to this study.

The study was supported by funding from the National Institutes of Health (grants R01 HL130020, R01 HL150693, R01 HL163680, R01 HL145676, P01 HL141084, R01 HL141371, R01 HL126527, R01 HL15864, R01 HL161002, R01 HL155282 and 18CDA34110293), an American Heart Association SFRN grant, an AHA Career Development Award and the Tobacco-Related Disease Research Program.

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Researchers solve mystery of how statins improve blood vessel health - Stanford Medical Center Report