Introduction to Statins
Statins are widely prescribed medications, with over 40 million Americans taking them to lower their cholesterol levels.
These drugs were developed in the 1980s and primarily target an enzyme that controls cholesterol production in the liver.
Despite their primary use, clinical trials have indicated that statins also offer protective benefits against cardiovascular disease beyond their cholesterol-lowering ability.
The underlying mechanisms for these effects, however, have been a mystery until now.
Broad Benefits of Statins: A Mystery Unraveled
Stanford Medicine researchers have used new genetic tools to study how statins work in human cells and mice.
Their study, published in Nature Cardiovascular Research, has shed light on how these cholesterol-lowering drugs protect the cells lining blood vessels.
Patients with heart failure who take statins are less likely to have a second heart attack. Statins have also shown to prevent arterial clogging, reduce inflammation, and even decrease cancer risk.
“This study gives us an understanding, at a very deep mechanistic level, of why statins have such a positive effect outside of reducing LDL or ‘bad’ cholesterol,” said Professor Joseph Wu, MD, Ph.D., of Stanford Medicine.
Detailed Study of Statins and Blood Vessels
To understand the effect of statins on blood vessels, the researchers tested a common statin, simvastatin, on lab-grown human endothelial cells.
These cells line our blood vessels and often transform into a different cell type, known as mesenchymal cells, in various diseases.
When treated with simvastatin, these endothelial cells formed more capillary-like tubes, a sign of improved ability to grow into new blood vessels.
Discovering the Mechanism: The Role of ATAC-seq
The breakthrough came when the researchers used a technique called ATAC-seq. This method illuminates what happens at the epigenetic level – changes to gene expression that do not involve changes to the genetic sequence.
ATAC-seq showed that the changes in gene expression resulted from the way DNA is packaged inside the cell nucleus.
DNA exists in our cells not as loose strands but as a series of tight spools around proteins, together known as chromatin. The exposure or concealment of specific DNA sequences in these spools determines their expression.
The researchers found that simvastatin-treated cells had closed chromatin structures that reduced the expression of genes triggering the endothelial-to-mesenchymal transition.
This process revealed that simvastatin prevents a protein known as YAP from entering the nucleus and opening chromatin.
Statins and Diabetes: Testing on Mice
The researchers then tested simvastatin on diabetic mice. Diabetes causes subtle changes to blood vessels that mimic the damage commonly seen in people who are prescribed statins.
The diabetic mice showed significantly improved vascular function after eight weeks on simvastatin, with arteries that relaxed and contracted more easily.
Conclusion: A Better Understanding of Statins
The findings offer a more detailed understanding of the vascular disease process, which could help doctors 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 impact on gene expression, and their potential for improving vascular function in conditions like diabetes.
“This study explains how statins work to provide vascular benefits,” said Professor Wu.
If you care about heart health, please read studies about COVID infection and vaccination linked to heart problems, and how to drink coffee to prevent heart disease and stroke.
For more information about heart health, please see recent studies about common food that may strongly increase heart disease risk, and results showing Vitamin K2 could help reduce heart disease risk.
The study was published in Nature Cardiovascular Research.
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