Coronary Vascular Rarefaction in Heart Failure

Coronary vasculature rarefaction has been thought to play a role in the development of heart failure (HF), causing reduced myocardial perfusion; understanding the role that coronary rarefaction plays within HF presents an avenue for therapeutic strategies. We assessed the coronary microvascular and small vessel networks in left atrial appendage (LAA) samples to determine differences based on HF status. LAA samples were obtained from 15 consecutive patients during cardiac surgery (BMI: 22.8-37.9, age: 51-82, M:F: 9:6, NonHF:HF: 11:4). LAA samples were paraffn-embedded or flash frozen whereby 40 μm thick sections were then immunolabelled using DyLight 594 fluorescent tomato-lectin dye and z-stack images were rendered using microscopy. Z-stack images were input into Vesselucida360 and the vessel networks were three-dimensionally reconstructed via unbiased automatic tracing with multiple quantitative endpoints calculated. LAA samples were also used for proteomic analysis via LC-MS followed by statistical and pathway analyses to determine differences in protein expression and pertinent pathways as well as in a wide-scale gene expression array (NanoString) to further study underlying molecular targets. We found that the number of branching nodes and total vessel length in the coronary vascular network was decreased in HF compared to NonHF patients. Whereas the total volume and surface area were similar between HF and NonHF patients. Proteomic analysis and principal component analysis identified differences in protein profiles in the two groups, with pathway analysis identifying cardiac contraction and metabolism, along with hydrogen peroxide catabolic pathways downregulated in HF. Gene expression profiling identified numerous hypoxia response and oxidative stress response markers as downregulated in HF LAA samples. The data obtained show coronary vascular rarefaction occurring in HF patients, implying potential implications in the progression of HF. Additionally, proteomic data point to the downregulation of hydrogen peroxide response pathways as a potential mechanism for coronary microvascular rarefaction that we want to elucidate in future studies. T32 HL155011 (KAF) F31 NS132564 (KAF). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.