Trimethylamine N-oxide (TMAO) is a biologically active molecule generated by the gut microbiota. Accumulating evidences have indicated a close association between high plasma TMAO levels and the risk of developing atherosclerosis (AS). AS is considered a chronic inflammatory disease initiated by vascular endothelial inflammatory injury. Both observational and experimental studies suggest that TMAO can cause endothelial inflammatory injury. However, a clear mechanistic link between TMAO and vascular inflammation of AS is not yet summarized. In this review, we discuss the association between TMAO and AS and focus on the potential role of TMAO in endothelial inflammatory injury. Finally, the utility of TMAO-targeted therapeutic strategies for the treatment of AS is also analyzed.

Abstract-The genetic analysis of hypertension has revealed complex and inconsistent results, making it difficult to draw clear conclusions regarding the impact of specific genes on blood pressure regulation in diverse human populations. Some of the confusion from previous studies is probably due to undetected gene-gene interactions. Instead of focusing on the effects of single genes on hypertension, we examined the effects of interactions of alleles at 4 candidate loci. Three of the loci are in the renin-angiotensin-system, angiotensinogen, ACE, and angiotensin II type 1 receptor, and they have been associated with hypertension in at least 1 previous study. The fourth locus studied is a previously undescribed locus, named FJ. In total, 7 polymorphic sites at these loci were analyzed for their association with hypertension in 51 normotensive and 126 hypertensive age-matched individuals. There were no significant differences between the 2 phenotypic classes with respect to either allele or genotype frequencies. However, when we tested for nonallelic associations (linkage disequilibrium), we found that of the 120 multilocus comparisons, 16 deviated significantly from random in the hypertensive class, but there were no significant deviations in the normotensive group. These findings suggest that genetic interactions between multiple loci rather than variants of a single gene underlie the genetic basis of hypertension in our study subjects. We hypothesize that such interactions may account for the inconsistent findings in previous studies because, unlike our study, prior studies almost always examined single-locus effects and did not consider the effects of variation at other potentially interacting loci. (Hypertension. 2000;36:2-6.)