Epigenetic Regulation of VCAM-1 During High-Altitude Exposure

Vascular Cell Adhesion Molecule-1 (VCAM-1) is a cell surface protein primarily expressed in vascular endothelial cells and primarily responsible for signaling for immune cell recruitment to vascular walls. However, VCAM-1 has also been implicated in several other mechanisms including localization of erythroid progenitor cells to the bone marrow and activation of CD4+T cells. Previous studies identified that plasma VCAM-1 protein levels are elevated at high altitude, potentially resulting from stress to the vascular endothelium. However, the precise mechanism underlying the increase is unclear and new evidence of shifts in immune cell populations and mobilization of extramedullary stress erythropoiesis may also contribute to this finding. We hypothesized that high altitude exposure leads to increased levels of circulating erythroid progenitor cells and VCAM-1 expressing T cells. We first measured VCAM1 gene expression and DNA methylation levels in peripheral immune cells collected from healthy individuals (N=10) at sea level and over 3 days of high-altitude exposure (3800 m elevation). Fasting blood samples were collected each morning for RNA sequencing and DNA methylation high-resolution melt analysis. We found that DNA methylation of VCAM1 decreased significantly (Kruskal-Wallis p=0.028) after 1 day of high-altitude exposure, then returned to baseline levels by day 3. However, this was not coupled with changes in VCAM1 gene expression after 1 or 3 days of high-altitude exposure (p >0.05). Together, this data provides evidence that VCAM1 undergoes hypomethylation in circulating immune cells, and future work will investigate the implications of these findings for immune and hematopoietic processes involved in acclimatization to hypoxia. Funding: This work was supported by a White Mountain Mini Grant to KP and a UC Riverside Regents Faculty Fellowship to ECH. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.