The heart is a vital part of the body that can last one hundred years, yet even a small change can cause massive consequences. Ischemic heart disease is one example where a lack of blood flow to the heart can cause tissue damage and, eventually, heart failure.
A common cause of ischemic heart disease is stenosis, aka the blockage of an artery. Coronary artery bypass grafting is considered the go-to treatment for such an issue. This surgery grafts healthy blood vessels before and after the blockage, essentially bypassing the problem. Unfortunately, the grafted blood vessels sometimes become inflamed, which can obstruct blood flow yet again.
The cause of this inflammation is thought to be the relatively high shear force the new blood vessels experience when they are grafted. When the healthy blood vessels are grafted into an area of high blood flow, the shearing forces cause damage and inflammation. This inflammation then causes a build-up of tissue as the graft remodels itself to withstand the forces, causing more blood flow restriction. The remodeling mechanism is not fully understood just yet, but a new study out of the University of Bristol sought to investigate.
The study focused on how the inflammatory signals in blood vessels changed when exposed to changes in shear forces. They examined the inflammatory signal molecules NF-kB (gene regulator) and CCL2 (pro-inflammatory signal) as markers in blood vessel cells in vitro, ex vivo, and in vivo.
They began by taking blood vessel grafts and exposing them to high shear stress in the lab. They saw that the inflammation marker CCL2 increased after exposure to the shear stress, and the activated transcription factor NF-kB. Inhibiting NF-kB reduced both activated NF-kB and CCL2 expression, inferring that NF-kB may be an upstream signal in the inflammation response.
The team saw the same results when they examined cardiac cells in vitro and decided to move onto the broader analysis. They investigated the protein expression profiles of blood vessel grafts exposed to either low or high shear stress. The grafts exposed to high shear stress again had higher NF-kB activation and CCL2 expression, both of which were reduced with an NF-kB inhibitor.
This study highlighted NF-kB’s role in the inflammation process in the grafts of coronary artery bypass graft surgery. As NF-kB inhibition managed to reduce inflammatory signals, this could lead to a post-surgery therapy that might reduce the inflammatory reaction and increase the likelihood of a successful outcome.
The study concludes, “we identified that acute arterial WSS is responsible for early pro-inflammatory activation of the LVG EC, a process regulated by NF-κB (p65) activation, resulting in upregulation of pro-inflammatory mediators and increased monocyte recruitment, thus, providing the first evidence for the mechanistic involvement of NF-κB in shear-induced inflammation in the vein graft endothelium.”