Researchers have identified a new molecular pathway involved in heart attacks and death from heart disease.
Publishing in the journal PLOS Genetics, they found that stress on a component of cells called the endoplasmic reticulum (ER) is associated with risk of future heart events, and it can be detected in bits of molecular detritus circulating in the blood.
The team focused on the intermediates between the genes and the disease pathway. This involved metabolomics -- an analysis of the metabolites, or trace chemicals, left behind as the byproducts from cellular processes.
Among a group of about 3,700 patients referred, the researchers performed a genome-wide analysis of specific metabolite levels that had previously been identified as predictors of cardiovascular disease.
In their earlier work, they had flagged these metabolites as markers for cardiovascular disease, but had not known how they were generated or what the underlying biological pathways were. The current study resolved that question, finding that these genes were directly linked to ER stress, which occurs when the endoplasmic reticulum organelle becomes overworked in its job managing excess and damaged cellular proteins.
They then took an epigenetics and transcriptomics approach to determine what the differences were between patients with high or low levels of metabolites. Once again, the ER stress pathway came up as a key component.