Endothelial dysfunction is a precursor and strong predictor of atherosclerosis which can lead to serious problems, including heart attack, stroke, or even death. Previous studies have linked the trillions of bacteria that colonize the gut and the development of atherosclerotic vascular diseases. In their report in Nature Communications, University of Iowa researchers led by Postdoctoral Associate Dr. Ajit Vikram in the laboratory of senior author Dr. Kaikobad Irani, Professor of Cardiovascular Medicine, describe a novel mechanism in which the gut microbiome signals through the blood stream to suppress the distal expression of the protein SIRT1, which is essential for maintenance of vascular health. Using a multifactorial approach including expression profiling, genetically modified rodents, broad spectrum antibiotics and high fat dietary regime the researchers demonstrated the regulation of SIRT1 in the endothelium occurs through modulation of the expression of a small non-coding RNA molecule, miRNA-204, in the wall of blood vessels. “This work illustrates a new mode of communication between bacteria in the gut and blood vessels, and how this communication leads to malfunction of blood vessels that can eventually precipitate plaque build-up and lead to heart disease” Vikram said.
University of Iowa researchers involved in the study were senior author Dr. Kaikobad Irani, Professor of Cardiovascular Medicine; lead author Dr. Ajit Vikram, Postdoctoral Associate; Dr. Young-Rae Kim, Postdoctoral Associate, Dr. Santosh Kumar, Postdoctoral Associate, Dr. Qiuxia Li, Postdoctoral Associate, Dr. Modar Kassan, Postdoctoral Associate, and Julia S. Jacobs, Senior Laboratory Technician.
*All researchers are affiliated with the Cardiovascular Division, Department of Medicine, University of Iowa Carver College of Medicine, Abboud Cardiovascular Research Center, University of Iowa Carver College of Medicine. Fraternal Order of Eagles Diabetes Research Center, University of Iowa., Pappajohn Biomedical Institute, University of Iowa.
The study was supported by the University of Iowa Endowed Professorship in Cardiovascular Medicine; National Institutes of Health grant T32 HL007344 and National Institutes of Health grant T32 HL007121