Atherosclerosis and Coronary Heart Disease
Buildup of plaque, as a result of the accumulation of cholesterol, oxidized lipids, leukocytes, cellular waste products, and calcium, inside the artery wall results in atherosclerosis and the narrowing of large and medium-sized arteries that can lead to coronary heart diseases and myocardial infarction. Artery wall metabolism, lipoproteins, immune system and coagulation factors play major roles in atherogenesis, narrowing of the arteries and eventual occlusion. Genetic and environmental factors affect the rate of atherogenesis in different individuals.
Current Research Projects
In addition, gut microbiota have now been associated with a variety of atherosclerosis risk factors, including plasma lipids, bile acids, insulin resistance, and inflammation. Recently, trimethylamine-N-oxide, a metabolite derived through the action of microbiota, was shown to be strongly associated with atherosclerosis. The participating laboratories (Jake Lusis, Mohamad Navab, Alan Fogelman) are primarily interested in mechanistic studies of host-microbiota interactions in mouse models. We are also carrying a large epidemiologic study on gut microbiota in a cross-sectional population from Finland.
We have observed that a number of peptides that suppress inflammation do so by acting at the level of the intestine, and we are exploring the possibility that their actions are mediated in part by effects on the gut microbiota. We have observed that upon feeding a diet containing a pro inflammatory lipid in LDL receptor null mice, the proportion of the P. Bacteriodeted and P. Verruccomicrobia was altered and our anti-inflammatory peptide reversed the changes.
- Navab M, Hough G, Buga GM, Su F, Wagner AC, Meriwether D, Chattopadhyay A, Gao F, Grijalva V, Danciger JS, Van Lenten BJ, Org E, Lusis AJ, Pan C, Anantharamaiah GM, Farias-Eisner R, Smyth SS, Reddy ST, Fogelman AM. Transgenic 6F tomatoes act on the small intestine to prevent systemic inflammation and dyslipidemia caused by Western diet and intestinally derived lysophosphatidic acid. J Lipid Res. 2013 Dec;54(12):3403-18. PMCID: PMC3826687.
- Navab M, Chattopadhyay A, Hough G, Meriwether D, Fogelman SI, Wagner AC, Grijalva V, Su F, Anantharamaiah GM, Hwang LH, Faull KF, Reddy ST, Fogelman AM. Source and role of intestinally derived lysophosphatidic acid in dyslipidemia and atherosclerosis. J Lipid Res. 2015 Apr;56(4):871-87. PMCID: PMC4373744.