Description:

Cori Cason, MD

Neointimal hyperplasia is a major contributor to restenosis after arterial interventions. The genetic and environmental mechanisms underlying the differences in the development of neointimal hyperplasia between individuals are not well understood. One possible modulator of neointimal hyperplasia severity between individuals is commensal gut microbes. We hypothesized that neointimal hyperplasia development after arterial injury in genetically different rat strains could be altered by commensal gut microbial transfer. In order to test this hypothesis, we cohoused genetically different rats (Lewis [LE] and Sprague-Dawley [SD]) which harbor different commensal microbes and compared neointimal hyperplasia 2 weeks after carotid angioplasty in the cohoused and non-cohoused cohorts. Cohousing is a means of microbial transfer between cage inhabitants. We observed that differences in neointimal hyperplasia between non-cohoused LE and SD rats (median intima+media [I+M] area 0.12 mm2 LE vs. 0.26 mm2 SD, P<.0001;Mann-Whitney) were mitigated when rats are cohoused for 1 month, suggesting an environmental effect that outweighs the genetic influence. Specifically, I+M area decreased by 23% in SD rats that were cohoused with LE rats (P<.0001;Mann-Whitney), and there was a trend towards a 10% increase in I+M area in cohoused LE rats. To identify specific bacteria associated with the change in neointimal hyperplasia, we monitored fecal bacteria over time using 16S rRNA sequencing. Principal component analysis revealed that fecal samples from cohoused rats diverged from non-cohoused rats in both strains (P<.001 SD, P=.008 LE;PERMANOVA) (Figure 1B). The greatest change was cohoused SD samples becoming similar to non-cohoused LE samples over time, which correlates with the carotid morphometric data. Comparative analysis showed that abundance of the bacterial genera Peptococcus and Blautia negatively correlated with I+M area in both strains (P<.001;Fisher z transform, Bonferroni corrected, Spearman’s ρ -0.8 for both). Ongoing studies will further delineate the potential causative relationship between these microbes and neointimal hyperplasia.