Multi-Omics Analysis Reveals Obesity-Independent, Heart Failure-Associated Phenotypic Changes in Coronary Perivascular Adipose Tissue

This dataset accompanies the study “Multi-Omics Analysis Reveals Obesity-Independent, Heart Failure-Associated Phenotypic Changes in Coronary Perivascular Adipose Tissue.” The study investigates depot-specific molecular and functional remodeling of coronary perivascular adipose tissue (PVAT) associated with heart failure with preserved ejection fraction (HFpEF) using a swine model of pacing-induced heart failure. Coronary PVAT surrounding the left anterior descending (LAD) artery was compared with subcutaneous adipose tissue (SUBQ) to determine whether heart failure produces distinct metabolic and lipidomic alterations in coronary-associated adipose tissue. Untargeted lipidomic and metabolomic profiling revealed marked depot-specific remodeling of LAD PVAT in HFpEF. Major molecular features included increased ether phospholipids, lysophospholipids, and polyunsaturated triglycerides, together with reduced levels of several diglyceride species. Pathway-level analyses further indicated alterations in fatty-acid elongation and desaturation and enhanced diglyceride-to-phosphatidylcholine (DG-to-PC) remodeling. In contrast, SUBQ adipose tissue exhibited comparatively modest metabolic changes, including alterations involving purine and glutathione metabolism. Metabolomic analysis of LAD PVAT also identified enrichment of pathways related to citrulline and arginine metabolism and nitric oxide (NO) signaling, supporting disruption of local NO/redox homeostasis in HFpEF. These molecular findings were complemented by functional vascular studies demonstrating that LAD PVAT from HFpEF animals enhanced KCl-induced vascular contraction and attenuated bradykinin-mediated relaxation, suggesting that HFpEF-associated remodeling of coronary PVAT may contribute to coronary vascular dysfunction. Overall, this dataset provides a resource for investigating the relationship between heart failure, coronary adipose tissue biology, lipid metabolism, redox signaling, and coronary vascular dysfunction, and supports the concept that HFpEF is associated with a distinct, depot-specific coronary PVAT phenotype. Associated manuscript Multi-Omics Analysis Reveals Obesity-Independent, Heart Failure-Associated Phenotypic Changes in Coronary Perivascular Adipose Tissue Authors: Praveen Kumar Guttula, Salman I. Essajee, Selina M. Tucker, Cooper M. Warne, Gregory M. Dick, Kirti Agrawal, Bruce A. Bunnell, Johnathan D. Tune, and Manas Ranjan Gartia. Keywords HFpEF; heart failure with preserved ejection fraction; perivascular adipose tissue; PVAT; coronary artery; LAD; lipidomics; metabolomics; multi-omics; lipid remodeling; fatty-acid metabolism; arginine metabolism; citrulline; nitric oxide; redox signaling; coronary microvascular dysfunction; swine model