"The target for this project is a novel approach addressing the infectious component of atherosclerosis, a disease which leads to myocardial infarction and stroke. Using immunology, cellular microbiology, genomics/metagenomics and fluorescence microscopy, our multidisciplinary team was the first to demonstrate vascular cell transmission of bacterial pathogens, the first to show association of dormant invasive bacteria with atheromatous tissue and, most importantly, the first to develop a technology to isolate and identify previously uncultivable bacterial pathogens from such tissues from patients.The objectives of this innovative proposal are to describe for the first time a critical for public health segment of the human microbiome, the atherosclerosis microbiome, to cultivate and identify its members and to determine the prevalence of these species in patients’ tissues. Further, we will examine the physiological capability of the pathogens to modulate 1) the lipid metabolism, 2) the pro-inflammatory response and 3) the viability of atheromatous tissue resident cell types, human phagocytic, endothelial and smooth muscle cells (SMCs). This will allow us to reveal the functional significance of the members of the atherosclerotic microbiome that may be critical for atherogenesis.This proposal builds on the excellence in the field of atherosclerosis research of the ICCC and of the Columbia University Medical Center in New York City. The deliverables of this project include much-awaited clarification of an entirely novel risk factor for atherogenesis that will benefit the majority of the EU population, at risk of number one cause of death. This focused project will define entirely novel targets for theragnostic clinical developments in the critical area of cardiovascular disease. Notably, bacterial infections can be a modifiable risk factor, making the accomplishment of this project a significant advancement, opening a new field in vascular medicine."