Blocking Blood Vessel Inflammation to Diminish Atherosclerosis
Researchers have a found a way to selectively interfere with inflammatory processes in blood vessel walls so as to slow the onset of atherosclerosis:
Normally, the lining of blood vessels, or endothelium [ignores] the many cells and other factors rushing by in the bloodstream. But in response to inflammatory signals, as well as other stimuli, endothelial cells change suddenly and dramatically - sending out beacons to attract inflammatory cells, changing their surface so those cells can stick to and enter tissues, and initiating a complex cascade of responses essential to fighting infection and dealing with injury. Unfortunately, these same endothelial responses also promote atherosclerosis, the build-up of plaque in arteries that cause heart attacks, strokes, and other inflammatory diseases.A [new study] is the first to demonstrate that BET bromodomain-containing proteins help execute inflammation in the endothelium while inhibition of BET bromodomain can significantly decrease atherosclerosis in vivo. "BET bromodomain-containing proteins have been studied in cancer for some time, where they are in therapeutic trials, but now we have mechanistic evidence for how BETs and their inhibition can impact endothelial inflammation and atherosclerosis."
In preclinical models, the researchers found that activating NF-kB, a canonical mediator of inflammation, rapidly redistributed the BET protein known as BRD4 to chromosomal sites where super enhancers driving expression of nearby inflammatory genes are located. Bromodomains are amino acid regions that bind to specifically modified sites on histones, the proteins around which DNA is coiled. By binding to these amino acid regions, BET bromodomain inhibitors block the assembly of protein complexes that drive expression of certain genes. In these studies, inhibiting BET bromodomains turned off an inflammatory program in human endothelial cells, decreased white blood cells adhering to endothelial cells, and decreased atherosclerosis in mice.
Link: http://news.harvard.edu/gazette/story/2014/09/a-way-to-inhibit-inflammation-of-blood-vessel-linings/
It seems a little bit insane that all these (clever and difficult) efforts are being made to slow things down a bit, yet no one ever thought to try the SENS approach of using enzymes to remove the oxidized LDL from the foam cells.