A research team led by Dr. Jason Fish of UHN and Nadiya Khyzha, a University of Toronto PhD candidate, has discovered a key mechanism that controls inflammation in blood vessels.
"We found a novel non-coding RNA," says Nadiya. "And it appears to regulate the levels of its closest neighbouring protein-coding gene, which is responsible for recruiting immune cells to blood vessels."
The team found a non-coding RNA that directs the production of a key protein that recruits inflammatory cells to blood vessels. They found that it is highly expressed in unstable plaques in blood vessels that feed the brain – which are prone to rupture – suggesting that this non-coding RNA may be involved in strokes and other inflammatory blood vessel diseases.
"The discovery that thousands of non-coding RNAs are present in the human genome adds an extra layer to the regulation of gene expression, yet the vast majority of non-coding RNAs remain uncharacterized," says Dr. Fish, Senior Scientist at the Toronto General Hospital Research Institute and the Peter Munk Cardiac Centre.
"Our study aimed to uncover functional non-coding RNAs involved in human vascular inflammation with the hopes of finding ways to fine-tune the inflammatory response."
Inflammation is often blamed for everything that ails us. From diabetes, to arthritis, to heart disease and cancer, inflammation seems to be at the core of ill health. And yet, without inflammation, we would be defenseless against infections and injuries.
As a double-edged sword, inflammation must be very carefully controlled.
"Inflammation is necessary for our survival," Nadiya says. "But too much can be harmful, so we need balance."
Only about one per cent of the DNA in our cells codes for proteins
The cells that line blood vessels (called endothelial cells) are one of the first lines of defense against infection. They send out protein messengers that tell immune cells in the blood that there is a problem, and these cells then home in on these areas to mount a formidable defense against invading pathogens.
However, the build-up of cholesterol in blood vessels can trigger these same signals, tricking the immune system into thinking it is attacking a foreign invader. Chronic inflammation is the collateral damage that is unleashed by this response, and the result is the formation of a plaque in the wall of blood vessels, which can rupture, leading to heart attack and stroke.
We know a lot about the protein messengers that direct the inflammatory process, but how they are controlled remains mysterious. Only about one per cent of the DNA in our cells codes for proteins, the rest is largely the "dark matter" of the genome.
Proteins are encoded by messenger RNAs, but there is an abundance of other RNAs that do not encode for proteins, which are referred to as non-coding RNA. Some of these non-coding RNAs can control the production of messenger RNAs.
Like an army commander directing a battalion against an invading enemy, these non-coding RNAs can direct which messenger RNAs (and therefore proteins) and how many, are sent into battle.
Their research was recently published in
Proceedings of the National Academy of Sciences of the United States of America, a leading scientific journal.
Read the study.
Now that they know of the existence and influence of this non-coding RNA, the hope is that in the future they can find a way to neutralize its negative effect in chronic blood vessel inflammation, while maintaining the body's ability to fight off infection.
It's a difficult balancing act, as inflammation can easily switch from friend to foe. Avoiding the "friendly fire" that occurs as the body attacks itself, may just win the war against inflammatory diseases, such as stroke.