Atherosclerosis is marked by the buildup of inflammatory cells which narrow arteries to the point of chest pain and muscle weakness. Severe cases result in lesions and internal ruptures of arteries or even thrombosis in coronary arteries.
One way that investigators are working to understand how atherosclerosis occurs and progresses is by looking at long non-coding RNAs (lncRNAs), strands of RNA that are not translated into proteins and which may play integral but understudied roles in cell regulation and disease progression. Through utilization of genetically modified high-risk atherosclerotic mice, a research team identified and characterized Macrophage-Associated Atherosclerosis lncRNA Sequence (MAARS), which is expressed specifically in macrophages in atherosclerotic plaques and contributes to the progression of the disease. Results are published in Nature Communications.
"We hypothesized, given the unknown role of lncRNAs, that some may be highly expressed in the blood vessel wall during the process of atherosclerosis," said the senior author. "We want to identify who these actors are, what they are doing, and how we can understand their function in a way that provides a foundation for future therapeutic opportunities."
The authors used genetically modified mice prone to atherosclerosis and placed them on a high cholesterol diet, which boosted their cholesterol to 500-1,000 units, up from a normal level of around 200 units. The mice were observed on their high cholesterol diet for 12 weeks, then placed on a normal diet and observed while their cholesterol levels returned to normal. Researchers isolated the innermost lining of the blood vessel walls of these mice and sent the samples for RNA sequencing to identify the presence of lncRNAs.
Among the list of present lncRNAs was MAARS, which piqued the interest of researchers with its specificity to macrophages and expression pattern. As atherosclerosis developed in the mice over the initial 12 weeks, the presence of MAARS increased 270-fold; once fed normal diets, the presence of MAARS decreased from its heightened expression by 60 percent. Targeted interruption of MAARS's function reduced atherosclerotic lesion formation by 52 percent by decreasing macrophage cell death and increasing efferocytosis -- the clearance of dead cellular debris -- from these lesions. These effects were largely independent of effects on circulating cholesterol.
Researchers found an important relationship between MAARS and an RNA-binding protein known as HuR. In the vessel wall, MAARS interacts with HuR, which plays a critical role in cell death. If MAARS is deliberately inhibited, HuR is released from the nucleus into the cytoplasm and the macrophages continue their cleaning. This chain of events leads to more active macrophages able to clean up more plaque and debris produced by atherosclerosis.
"lncRNAs play a really important role in cardiovascular disease," said the senior author. "We had no idea what we were going to find, and we ended up identifying a lncRNA that has a crucial role in macrophages and pathways that could have therapeutic potential. We are shedding light on new players in old signaling pathways. It is so exciting to add more nuance to this area of research, since that means future studies will have that much more to work with."
https://www.nature.com/articles/s41467-020-19664-2
http://sciencemission.com/site/index.php?page=news&type=view&id=publications%2Fa-macrophage-specific&filter=22
Long non-coding RNA's role in cardiac plaque build-up
- 960 views
- Added
Edited
Latest News
Metabolic rewiring promotes…
By newseditor
Posted 18 Apr
A drug to prevent flu-induc…
By newseditor
Posted 18 Apr
New origin of deep brain waves
By newseditor
Posted 17 Apr
Starving cells hijack prote…
By newseditor
Posted 17 Apr
Miniature battery-free epid…
By newseditor
Posted 17 Apr
Other Top Stories
Artificially infect mosquitoes with human malaria to identify new c…
Read more
Local immune response to food antigens drives meal-induced abdomina…
Read more
Highly specific single-chain multivalent nanobodies against SARS-C…
Read more
Strong link between gut microbes, diet and health in humans
Read more
Characterization of a new Leishmania major strain for use in a cont…
Read more
Protocols
MemPrep, a new technology f…
By newseditor
Posted 08 Apr
A tangible method to assess…
By newseditor
Posted 08 Apr
Stem cell-derived vessels-o…
By newseditor
Posted 06 Apr
Single-cell biclustering fo…
By newseditor
Posted 01 Apr
Modular dual-color BiAD sen…
By newseditor
Posted 31 Mar
Publications
How does the microbiota con…
By newseditor
Posted 18 Apr
The integrated stress respo…
By newseditor
Posted 18 Apr
The immunobiology of herpes…
By newseditor
Posted 17 Apr
Circulating microbiome DNA…
By newseditor
Posted 17 Apr
Spindle oscillations in com…
By newseditor
Posted 17 Apr
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar