From Prevention to Disease Perturbations: A Multi-Omic Assessment of Exercise and Myocardial Infarctions

Abstract

While a molecular assessment of the perturbations and injury arising from diseases is essential in their diagnosis and treatment, understanding changes due to preventative strategies is also imperative. Currently, complex diseases such as cardiovascular disease (CVD), the leading cause of death worldwide, suffer from a limited understanding of how the molecular mechanisms taking place following preventive measures (e.g., exercise) differ from changes occurring due to the injuries caused from the disease (e.g., myocardial infarction (MI)). Therefore, this manuscript assesses lipidomic changes before and one hour after exercise treadmill testing (ETT) and before and one hour after a planned myocardial infarction (PMI) in two separate patient cohorts. Strikingly, unique lipidomic perturbations were observed for these events, as could be expected from their vastly different stresses on the body. The lipidomic results were then combined with previously published metabolomic characterizations of the same patients. This integration provides complementary insights into the exercise and PMI events, thereby giving a more holistic understanding of the molecular changes associated with each.

Deciphering ApoE Genotype-Driven Proteomic and Lipidomic Alterations in Alzheimer’s Disease Across Distinct Brain Regions

“…Lipid identifications were made based on AMT matching in LIQUID software using the LIQUID library . Comparable coverage to other lipidomic investigations of biological samples implementing the same methodology and using multidimensional confidence criteria was observed. ,,− Here, a total of 294 lipids were confidently identified with 173 and 121 lipids observed across positive and negative ionization modes based on LC, IMS and MS matching. Lipid assignments were based on combined LC, IMS, and MS/MS experimental evidence and typically included headgroup and fatty acyl assignment (i.e., PC(16:0_18:1)).…”

Comprehensive Metabolomic Analysis of Human Heart Tissue Enabled by Parallel Metabolite Extraction and High-Resolution Mass Spectrometry

“…The heart contracts incessantly to supply oxygenated blood to the entire body and thus, requires a constant source of energy to fuel its high energy demands . The heart is a “metabolic omnivore” that utilizes a variety of fuel substrates, ranging from very polar (e.g., amino acid and nucleosides) to very nonpolar (e.g., lipids). − Therefore, a comprehensive metabolomic analysis is critical to understanding cardiac metabolism; however, it remains challenging as the broad range of metabolite polarities makes extraction and detection difficult. − …”

Comprehensive Metabolomic Analysis of Human Heart Tissue Enabled by Parallel Metabolite Extraction and High-Resolution Mass Spectrometry

“…1 The heart is a "metabolic omnivore" and utilizes a variety of fuel substrates, ranging from very polar (e.g., amino acid and nucleosides) to very non-polar (e.g., lipids). [2][3][4][5][6] Therefore, a comprehensive metabolomic analysis is critical to understand cardiac metabolism; however, it remains challenging as the broad range of metabolite polarities makes extraction and detection difficult. [7][8][9][10][11][12][13][14] First it is critical to effectively extract metabolites in a comprehensive and reproducible manner.…”