Fibrosis process activation in patients with acute cardiac rejection: A novel noninvasive diagnostic approach

ABSTRACT: Cardiac allograft fibrosis is an important limiting factor for long-term graft survival. However, the fibrotic process operating in patients with acute cellular rejection (ACR) remains unclear. We aimed to identify serum mRNAs related to cardiac fibrosis whose relative abundance become altered in patients with ACR and to evaluate their diagnostic accuracy in detecting rejection episodes. A total of 40 serum samples from recipients of transplants undergoing routine endomyocardial biopsies were included in an RNA sequencing analysis that included 28 diagnosed with ACR (grade 1R, n=16; and grade ≥2R, n=12) and 12 without cardiac rejection. We detected several altered mRNAs associated with fibrosis in patients with ACR. Specifically, the activators of fibroblasts and myofibroblasts (TNS1, FAP and ACTA2; p<0.05), TGF-β signaling (TGFBR1 and JAK1; p<0.05) and WNT signaling (WNT7A and WLS; p<0.01) pathways showed significant differences in their relative abundance when we compared grade ≥2R ACR and/or grade 1R ACR groups with the nonrejection group. Further, TNS1 and WLS presented an area under the curve value >0.90 for identifying patients with moderate and severe grades of cardiac rejection. In conclusion, we found alterations in the relative abundance of circulating activators of fibroblasts and myofibroblasts, such as FAP or ACTA2, as well as in major profibrotic pathways, including TGF-β and WNT signaling, especially in clinically relevant cardiac rejection. These findings may contribute to improving the surveillance of patients with cardiac transplant and provide new therapeutic strategies for targeting fibrosis. Future studies in larger cohorts are needed to better understand the potential impact of confounding variables.

ORGANISM(S): Homo sapiens

PROVIDER: GSE315025 | GEO | 2026/07/01

REPOSITORIES: GEO