Researchers at the UR Medical Center are one step closer to understanding how to counter atherosclerosis, a potentially life threatening condition that can lead to heart attacks and strokes.
The disease is caused by fatty buildup along the walls of arteries. This buildup eventually blocks blood flow, leading to serious health problems.The idea behind the new research is that strong, steadfast blood flow helps to prevent the blockage of arteries.
In a recently published article in the journal ‘Blood,” UR researchers claim that they are very close to being able to mimic every step of a complex natural chain reaction that takes place in the body. The reaction enhances blood flow, which in turn reduces dangerous fatty buildup.
‘If we can understand this mechanism, then we can construct a drug to mimic the pathway. That is the simple thought behind this research,” Associate Professor of Medicine in the Cardiovascular Research Institute Zheng-Gen Jin said.
Past research has already revealed that blood flow force prevents atherosclerosis by activating two key genes, known as KLF2 and eNOS. Research at the URMC is concerned with why this happens knowledge that is pivotal in the design of medication to prevent the disease. UR researchers are very close to understanding the answer to this question.
URMC research has determined that the blood flow force generates a structural transformation of an enzyme known as HDAC5. It is this transformation that causes the stimulation of the two genes, KLF2 and eNOS.
Currently, research is concentrated on a specific process called phosphorylation, which ties the force of blood flow and HDAC5 together in the prevention of atherosclerosis.
It is a process in which a specific enzyme, called a kinase, attaches an arrangement of molecules, called a phosphate group, to a specific target in order to stimulate or inhibit a specific process. In this case, phosphorylation triggers HDAC5 to exit the cell nucleus, which emerging research suggests is a key factor in atherosclerosis prevention.
Weiye Wang, a member of the Cardiovascular Research Institute, constructed a virus to halt the phosphorylation that is caused by blood flow force. HDAC5 did not leave the nucleus once the virus was introduced, proving that the phosphorylation due to blood flow force is essential in inhibiting atherosclerosis.
Researchers also discovered that when HDAC5 is exported out of the nucleus, it is detached from a molecule called MEF2, which stimulates KLF2 and eNOS, the two key genes in the prevention of blood vessel clogging. When HDAC5 failed to leave the nucleus, it was unable to activate these genes.
This breakthrough has significance not just in preventing atherosclerosis, but also in minimizing blood clotting in general.
‘[This] promises to be extremely useful, potentially to stave off disease underway in the blood vessels of humans,” Jin said.
UR researchers’ studies on blood flow began about 30 years ago, when they found that strengthening health through exercise allows it to pump blood with more power, increasing the force of blood flow through the arteries and preventing the clogging of fatty materials.
Now, researchers in the department are close to understanding this process in greater depth than ever before.
Negri is a member of the class of 2012.
