Multiomics investigation of the female hypertensive human heart

Area of Science:

• Cardiovascular Biology
• Molecular Cardiology
• Human Pathology

Background:

• Hypertension is a major risk factor for heart disease, affecting millions globally.
• Existing knowledge relies heavily on animal models, lacking human cardiovascular tissue insights.
• Previous work established a protocol for preserving postmortem human hearts for research.

Purpose of the Study:

• To investigate the molecular changes in adult human hearts associated with hypertension.
• To utilize multiomics analyses on postmortem cardiac tissue.
• To establish a foundation for studying human cardiovascular disease.

Main Methods:

• Pilot multiomics analyses (bulk RNA-seq, single-nucleus RNA-seq, metabolomics) on postmortem human hearts.
• Comparison between hearts from donors with hypertension (n=3) and without (n=2).
• Systematic dissection and preservation of whole human hearts.

Main Results:

• Hypertension linked to increased transcripts for DNA helicase activity, NAD-dependent deacetylase activity, and branched-chain amino acid metabolism.
• Single-nucleus RNA-seq revealed loss of contractile vascular smooth muscle cells and increased endothelial cell proliferation in hypertensive hearts.
• Metabolomics indicated reductive stress and altered metabolic pathways, including fatty acid oxidation and the pentose phosphate pathway.

Conclusions:

• Multiomics analysis of postmortem human hearts is a viable method for cardiovascular disease research.
• Identified molecular signatures of hypertension in adult cardiac tissue, including cellular and metabolic alterations.
• Provides novel human-based molecular insights into hypertension's cardiac impact.