Researchers solve mystery of how statins improve blood vessel health (Simvastatin)

Medical Xpress / Stanford Cardiovascular Institute / Nature Cardiovascular Research ^ | May 11, 2023 | Nina Bai / Chun Liu et al

[ConservativeMind]

Using new genetic tools to study statins in human cells and mice, researchers have uncovered how the cholesterol-lowering drugs protect the cells that line blood vessels.

The findings provide new insight into statins' curiously wide-ranging benefits, for conditions ranging from arteriosclerosis to diabetes, that have long been observed in the clinic.

Liu tested simvastatin on lab-grown human endothelial cells. Endothelial cells make up the lining of blood vessels, but in many diseases they transform into a different cell type, known as mesenchymal cells.

"Mesenchymal cells are less functional and make tissues stiffer so they cannot relax or contract correctly," Liu said.

The researchers suspected that statins could reduce this harmful transition. Indeed, endothelial cells treated with simvastatin in a dish formed more capillary-like tubes, a sign of their enhanced ability to grow into new blood vessels.

RNA sequencing of the treated cells offered few clues. The researchers "didn't find anything interesting," Liu said.

It was not until they employed a newer technique called ATAC-seq that the role of statins became apparent.

DNA exists in our cells not as loose strands but as a series of tight spools around proteins, together known as chromatin.

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.

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

[El Laton Caliente]

The wife is trying flush niacin to lower cholesterol.