Skip to main content
 
Notice: Users may be experiencing issues with displaying some pages on stanfordhealthcare.org. We are working closely with our technical teams to resolve the issue as quickly as possible. Thank you for your patience.
Stanford Health Care

Integrated multiomics of pressure overload in the human heart prioritizes targets relevant to heart failure.

Integrated multiomics of pressure overload in the human heart prioritizes targets relevant to heart failure. Nature communications Lindman, B. R., Perry, A. S., Lance, M. L., Amancherla, K., Kim, N., Sheng, Q., Lin, P., Pfeiffer, R. D., Farber-Eger, E., Fearon, W. F., Kapadia, S., Kumbhani, D. J., Gillam, L., Mallugari, R. R., Gupta, D. K., Miller, F. J., Vatterott, A., Jackson, N., Su, Y. R., Tomasek, K., Absi, T., Freedman, J. E., Nayor, M., Das, S., Wells, Q. S., Dweck, M. R., Gerszten, R. E., Gamazon, E. R., Tucker, N. R., Shah, R., Elmariah, S. 2025; 16 (1): 6889

Abstract

Pressure overload initiates a series of alterations in the human heart that predate macroscopic organ-level remodeling and downstream heart failure. We study aortic stenosis through integrated proteomic, tissue transcriptomic, and genetic methods to prioritize targets causal in human heart failure. First, we identify the circulating proteome of cardiac remodeling in aortic stenosis, specifying known and previously-unknown mediators of fibrosis, hypertrophy, and oxidative stress, several associated with interstitial fibrosis in a separate cohort (N=145). These signatures are strongly related to clinical outcomes in aortic stenosis (N=802) and in broader at-risk populations in the UK Biobank (N=36,668). We next map this remodeling proteome to myocardial transcription in patients with and without aortic stenosis through single-nuclear transcriptomics, observing broad differential expression of genes encoding this remodeling proteome, featuring fibrosis pathways and metabolic-inflammatory signaling. Finally, integrating our circulating and tissue-specific results with modern genetic approaches, we implicate several targets as causal in heart failure.

View details for DOI 10.1038/s41467-025-62201-2

View details for PubMedID 40715126