Study shows how blood flow force prevents heart attack and stroke
Researchers are closer to understanding exactly how blood flow force through the arteries prevents heart attack and stroke. Exercise is well known for its role in heart attack and stroke prevention, but the exact reason exercise protects is through a series of reactions that occur in the lining of the blood vessels related to force of blood flow.
New research conducted at the University of Rochester Medical Center suggest that the enzyme histone deacetylase 5 (HDAC5) is influenced by blood flow. Two genes, Krüppel-like factor 2 (KLF2) and endothelial nitric oxide synthase (eNOS), are switched on by blood flow force to reverse atherosclerosis. The study showed for the first time that it is blood flow force that triggers the HDAC5 enzyme that subsequently turns on the two genes to reverse buildup of artery plaque, or atherosclerosis.
“Obviously we should all be exercising to get our hearts pumping fast, which increases blood flow force through our vessels with all of these molecular benefits," said Zheng-Gen Jin, Ph.D., associate professor of Medicine within the Aab Cardiovascular Research Institute (CVRI) at the University of Rochester Medical Center, and corresponding author for the study. "
The study results show that through a signaling process that turns life forces on and off, phosphorylation occurs. Enzymes called kinases attach a set of molecules called a phosphate group that kicks the enzyme HDAC5 that influences blood flow out of the cell's nucleus. The researchers discovered that force of blood flow indeed facilitated transport of HDAC5 from cells that line the blood vessels, resulting in phosphorylation. The researchers also found that blood flow forces HDAC5 to break away from myocyte enhancer factor-2 (MEF2), the molecule it normally attaches to. MEF2 that is free of HDAC5 more nitric oxide and blood vessel relaxation occurred, increasing blood flow and lowering blood pressure.
The researchers discovered the how force of blood flow can keep arteries healthy to prevent heart attack, stroke and other diseases of the blood vessels by designing a virus to invade the cells and swap out the key building blocks that make phosphorylation via blood flow force possible.
A second and important finding from the study was the buildup of white blood cells in the arteries that happens in the absence of phosphorylation. Blood flow force prevents stroke and heart attack by driving expression of Krüppel-like factor 2 that prevents inflammation and blood clots in the arteries.
"If we could free MEF2 from HDAC5 with a drug, we could mimic flow force to enhance KLF2 and eNOS expression and reverse inflammation in vessel walls," Jin said. "That promises to be extremely useful, and potentially to stave off disease underway in the blood vessels of humans."
In the meantime, vigorous exercise that increases blood flow force through the arteries can trigger a series of reactions that prevents clogged arteries and protects from heart attack and stroke. The researchers still have more to learn about how force of blood flow leads to the essential process of phosphorylation that protects the arteries from inflammation and disease.