Statins: protecting blood vessels beyond lowering cholesterol

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Statins, cholesterol-lowering medications taken by over 40 million Americans, have been found to provide benefits beyond just reducing “bad” cholesterol.

A recent study has provided insights into how these drugs protect the cells lining blood vessels, offering potential explanations for their broad health benefits observed in the clinic, including in conditions like arteriosclerosis and diabetes.

Statins were initially developed in the 1980s to regulate cholesterol production in the liver. Clinical trials, however, have shown they also protect against cardiovascular disease beyond their cholesterol-lowering capacity.

For instance, heart failure patients on statins are less likely to have a second heart attack, and the drugs are also associated with the prevention of artery clogging, reduction of inflammation, and even lower cancer risk.

The exact mechanisms behind these benefits have remained unclear.

In a study published in Nature Cardiovascular Research, the team focused on statins’ effects on endothelial cells, which form the lining of blood vessels.

These cells can transform into a different cell type, mesenchymal cells, in various diseases, leading to tissue stiffness and impacting their ability to relax or contract.

The researchers, using lab-grown human endothelial cells, found that statins could reduce this harmful transition.

Using a technique called ATAC-seq, they discovered that the drugs caused changes at the epigenetic level, altering gene expression without changing the genetic sequence.

Specifically, statins were found to prevent a protein known as YAP from entering the cell nucleus and opening chromatin (a complex of DNA and protein), which in turn reduced the expression of genes causing the endothelial-to-mesenchymal transition.

When tested on diabetic mice, a condition that causes subtle vascular changes similar to those seen in older statin-prescribed patients without cardiovascular conditions, simvastatin significantly improved vascular function over an eight-week period.

This new understanding of statins’ mechanism could allow for the fine-tuning of the drug to be more specific to rescuing vascular function, as well as providing a more detailed picture of the vascular disease process, aiding doctors in early detection and treatment of vascular damage.

The study was a collaborative effort involving researchers from Stanford, the University of North Texas, and the Ohio State University College of Medicine, with funding provided by the National Institutes of Health, the American Heart Association, and the Tobacco-Related Disease Research Program.

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The study was published in Nature Cardiovascular Research.

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