Liver Protein May Be Link To Heart Disease

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Scientists at the University of Michigan Medical School have identified a liver protein that triggers an inflammatory response in the liver and also may be involved in the development of coronary artery disease.

The protein, called CREBH, is a transcription factor that turns on the activity of specific genes in liver cells. According to U-M scientists, CREBH is activated in response to cellular stress generated when unfolded proteins clog the endoplasmic reticulum - the part of a cell where new proteins are made.

"This is the first evidence indicating that an acute inflammatory response in the liver can be triggered by stress in the endoplasmic reticulum," says Randal J. Kaufman, Ph.D., a Howard Hughes Medical Investigator and professor of biological chemistry in the U-M Medical School, who directed the research study.

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Results of the study will be published in the Feb. 10 issue of Cell.

Scientists have known for some time that immune system cells release biochemical signals called cytokines, which travel through the bloodstream and activate an inflammatory response elsewhere in the body. But no one knew that liver inflammation could be triggered by signals from individual liver cells.

"Our study shows a direct connection between stress in the endoplasmic reticulum and the inflammatory response in the liver," adds Kezhong Zhang, Ph.D., a U-M research investigator and the paper's first author. "The link to heart disease is intriguing, because inflammation could be induced by several factors - infection, use of alcohol or a western-style diet - that cause ER stress and they are all potential risk factors for heart disease."

U-M researchers discovered that CREBH regulates production of C-reactive protein (CRP), which is often found at elevated levels in the blood of heart attack patients and patients with autoimmune diseases. They also found evidence that CREBH is involved in production of apolipoprotein B (ApoB).

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