An Untargeted LC–MS based approach for identification of altered metabolites in blood plasma of rheumatic heart disease patients

Abstract

Rheumatic heart disease (RHD) is often considered as a disease of developing countries and India is the home of about 40% of RHD patients. Environment seems to play a major role in its causation. Since gene environment interactions can lead to alterations of various metabolic pathways, identification of altered metabolites can help in understanding the various pathways leading to RHD. Blood plasma samples from 51 RHD and 49 healthy controls were collected for the study. Untargeted metabolomics approach was used to identify the metabolites that are altered in RHD patients. Data showed 25 altered metabolites among RHD patients. These altered metabolites were those involved in Purine, Glutamine, Glutamate, Pyrimidine, Arginine, Proline and Linoleic metabolism. Thus, the present study illuminates metabolic alterations among RHD patients which can help in determining the potential therapeutic targets.

A study protocol to characterise pathophysiological and molecular markers of rheumatic heart disease and degenerative aortic stenosis using multiparametric cardiovascular imaging and multiomics techniques

“…Proteomic studies on AS and RHD have led to an enhanced understanding of the molecular mechanisms leading to the valve pathologies observed in AS and RHD patients [ 31 ]. However, very few metabolomics studies have investigated the metabolic pathomechanisms involved in RHD [ 39 ].…”

“…The incidence of RHD in particular is much greater in LMICs than in high-income countries, and the increasing incidence of degenerative calcific aortic stenosis complicates the diagnosis and management of valvular heart disease patients [ 3 ]. Few studies have explored biomarkers to understand the pathomechanisms of rheumatic heart disease [ 10 , 13 , 22 , 24 , 39 ]. Therefore, we hypothesise that our proposed study will report on common and differential biomarkers associated with degenerative aortic stenosis and rheumatic heart disease in the African population.…”

“…Despite the high prevalence of RHD and AS in Africa, understanding of their pathogenesis has been elusive. The molecular mechanisms involved in the pathophysiology of RHD are not well understood [ 10 , 39 ]. In addition, very few studies have compared the molecular mechanisms underlying RHD and degenerative aortic stenosis despite having different etiologies.…”

Metabolome Profiling in the Plasma of Dogs with Idiopathic Dilated Cardiomyopathy: A Multiplatform Mass-Spectrometry-Based Approach

“…The investigation of blood plasma of rheumatic heart disease of patients by an untargeted LC-MS-based approach indicated an increased level of orotate. The increased level of orotate can be an indicator of a protective mechanism in patients with rheumatic heart disease [59]. On the other hand, the study of Williams et al (1991) showed that administration of the metabolite orotate increases the pyrimidine nucleotide content in heart tissue [60].…”

Structural Elucidation of 3-Nitrophenylhydrazine Derivatives of Tricarboxylic Acid Cycle Acids and Optimization of Their Fragmentation to Boost Sensitivity in Liquid Chromatography-Mass Spectrometry

“…However, their derivatization to less polar species helps to enhance screening coverage in LC-MS-based applications that require separation of metabolites with wide range of polarities [29,30]. In present study we used 3-NPH-derivatization that is commonly used for analysis of many biological relevant metabolites such as short-chain fatty acids [18,31] and other carbonyl-, carboxyl-, and phosphoryl-containing metabolites [19,20,32]. The derivatization strategy was applied to untargeted analysis of human plasma to identify not only TCA carboxylates but also fatty acids.…”