How statins improve blood vessel health


Introduction to Statins
Statins are a commonly prescribed medication used by over 40 million Americans to lower their cholesterol levels.
Developed in the 1980s, these drugs primarily target an enzyme that controls cholesterol production in the liver.
Despite their primary use, clinical studies have shown that beyond their cholesterol-lowering effects, statins also provide protective benefits against cardiovascular disease.
However, the underlying mechanisms of these effects have so far been a mystery.
Extensive Benefits of Statins: A Mystery Solved
Stanford Medicine researchers have used new genetic tools to study how statins work in human cells and mice.
Their study, published in Nature Cardiocular Research, has shed light on how these cholesterol-lowering drugs protect the cells that line blood vessels.
Heart failure patients who take statins have a reduced risk of having a second heart attack. Statins have also been shown to prevent clogged arteries, reduce inflammation, and even lower the risk of cancer.
“This study gives us an understanding at a very deep mechanistic level of why statins have such a beneficial effect that goes beyond lowering LDL or ‘bad’ cholesterol,” said Professor Joseph Wu, MD, Ph.D., of Stanford Medicine.
Detailed study of statins and blood vessels
To understand the effects of statins on blood vessels, the researchers tested a common statin, simvastatin, on laboratory-grown human endothelial cells.
These cells line our blood vessels and often transform into another type of cell called mesenchymal cells in various diseases.
When treated with simvastatin, these endothelial cells formed more capillary-like tubes, a sign of an improved ability to grow into new blood vessels.
Discovering the Mechanism: The Role of ATAC-seq
The researchers got their breakthrough when they used a technique called ATAC-seq. This method sheds light on what is happening at the epigenetic level – changes in gene expression that do not involve changes in the genetic sequence.
ATAC-seq showed that the changes in gene expression are due to the way DNA is packaged in the nucleus.
DNA does not exist in our cells as loose strands, but as a series of tight coils wrapped around proteins known collectively as chromatin. The revealing or hiding of specific DNA sequences in these coils determines their expression.
The researchers found that cells treated with simvastatin had closed chromatin structures that reduced the expression of genes that trigger the transition from endothelium to mesenchyme.
This process revealed that simvastatin prevented a protein called YAP from entering the nucleus and opening up the chromatin.
Statins and diabetes: tests in mice
The researchers then tested simvastatin on diabetic mice. Diabetes causes minor changes in blood vessels that resemble the damage that often occurs in people prescribed statins.
After eight weeks of treatment with simvastatin, the diabetic mice showed significantly improved vascular function, with the arteries relaxing and contracting more easily.
Conclusion: A better understanding of statins
The results allow for a more detailed understanding of the vascular disease process and could help physicians identify and treat early signs of vascular damage.
The study provides valuable insight into the benefits of statins, including a deeper understanding of how they protect blood vessels, their effects on gene expression, and how they may improve vascular function in conditions like diabetes.
“This study explains how statins provide vascular benefits,” Professor Wu said.
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The study was published in natural cardiovascular research.
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