Key Protein That Binds to LDL Cholesterol Identified
News Nov 21, 2016
A Yale-led research team identified a protein that plays an important role in the buildup of LDL cholesterol in blood vessels. The finding could lead to an additional strategy to block LDL accumulation, which could help prevent or slow the clogging of arteries that leads to heart disease, the researchers said.
The study was published on Nov. 21 in Nature Communications.
Arteries become clogged with fats and cholesterol when certain proteins in the body, known as lipoproteins, combine with and transport fats in the blood to cells. Scientists have long believed that the LDL receptor molecule was responsible for the transport of LDL within cells. But given that some individuals lacking the LDL receptor still have high levels of LDL, questions remained about the mechanism.
To identify the mechanism, the research team screened more than 18,000 genes from the endothelium — the inner layer of human blood vessels. They examined the transfer of LDL into endothelial cells and then focused on possible genes involved in the process.
The researchers found that a protein called ALK1 facilitated LDL’s pathway into cells. “We confirmed that ALK1 directly binds to LDL,” said William C. Sessa, senior author and the Alfred Gilman Professor of Pharmacology and professor of medicine (cardiology). The team also determined that the “LDL-ALK1 pathway” aided the transport of LDL from blood into tissue.
The role of ALK1 in LDL accumulation was not previously known, said Sessa.
“The discovery of ALK1 as an LDL-binding protein implies that it might initiate the early phases of atherosclerosis,” he noted. “If we can find a way of blocking ALK1 using small molecules or antibodies, it might be used in combination with lipid-lowering strategies.”
Current lipid-lowering strategies include statins, which target LDL cholesterol levels in the blood.
A therapeutic that blocks ALK1 “would be a unique strategy for reducing the burden of atherosclerosis and be synergistic with lipid- lowering therapies,” Sessa noted.
Story from Yale University. Original piece written by Ziba Kashef. Please note: The content above may have been edited to ensure it is in keeping with Technology Networks’ style and length guidelines.
Kraehling, J. R., Chidlow, J. H., Rajagopal, C., Sugiyama, M. G., Fowler, J. W., Lee, M. Y., … Sessa, W. C. (2016). Genome-wide RNAi screen reveals ALK1 mediates LDL uptake and transcytosis in endothelial cells. Nature Communications, 7, 13516. doi:10.1038/ncomms13516
Bacterial Control Mechanism for Adjusting to Changing ConditionsNews
A fundamental prerequisite for life on earth is the ability of living organisms to adapt to changing environmental conditions. Physicists have now determined that the regulation mechanisms used by bacteria to adapt to different environments are based on a global control process that can be described in a single equation.READ MORE
Cracking the Code of Coenzyme Q BiosynthesisNews
Coenzyme Q is a vital cog in the body’s energy-producing machinery, a kind of chemical gateway in the conversion of food into cellular fuel. Researchers are developing new tools to shed light on CoQ function, primarily by finding and defining proteins that have a direct link to the chemical. This includes the development of a new multi-omic strategy to identify the global function of an RNA-binding protein that has long been associated with mitochondria and its role in CoQ biosynthesis.READ MORE
CMC Biologics Announces Development and Manufacturing Agreement with Harpoon TherapeuticsNews
Companies have entered into agreement for the development and manufacturing of three TriTAC molecules for the treatment of cancers.READ MORE