Inflammation is an acute response to injury and protracted inflammation leads to development of vascular disease. Interleukin-8 (IL-8) is a potent inflammatory factor known to be highly associated with cardiovascular disease and can be served as an independent biomarker for the prediction of cardiovascular events. However, whether IL-8 is the causative factor in vascular disease progression remains uncertain, and the regulation of IL-8 during disease progress is also unknown. Moreover, our recent RNA-sequencing data have identified a novel long non-coding RNA KILN, a neighbor gene of IL-8, regulating IL-8 expression and inflammation in vascular smooth muscle cells (VSMCs). However, the in vivo function of KILN or regulation of KILN on IL-8 and inflammation during disease progress is completely unknown. The proposed study aims to unravel the contribution of this novel gene pair, IL-8 and KILN to vascular diseases, using a humanized bacterial artificial chromosome (BAC) mouse that encompasses the human specific gene pair IL-8 and KILN. This proposal will also gain some insight into the mechanism underlying inflammation-associated vascular pathogenesis. As a consequence of these studies, I expect to provide the first direct evidence supporting the causative role of IL-8, and its novel neighbor gene KILN, in the progression of vascular disease. It will open avenues to future endeavors for novel therapeutic targets.
|Program type||Career Development Award|
|Effective start/end date||07/01/2018 → 06/30/2021|