Relationship between the plasma acylcarnitine profile and cardiometabolic risk factors in adults diagnosed with cardiovascular diseases

Кухаренко, А. В.; Brito, Alex; Kozhevnikova, Maria; Moskaleva, Natalia E.; Markin, Pavel A.; Bochkareva, N. L.; Korobkova, E O; Belenkov, Y.; Привалова, Е. В.; Larcova, E V; Ariani, Andrea; Frano, Michael R. La; Appolonova, Svetlana A.

doi:10.1016/j.cca.2020.04.035

Cited by 26 publications

(17 citation statements)

References 29 publications

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“…The module including cofactors and vitamins involved in ascorbate/aldarate (i.e., oxalate) metabolism among other sub pathways, was significantly higher in females and lower among current smokers. This confirms previous observations of lower metabolite abundances in those pathways among cigarette smokers, but also adds a novel sex specific association for future research [34,35].…”

Section: Discussionsupporting

confidence: 89%

“…The sex-specific associations for acylcarnitines and COPD may be related to mitochondrial dysfunction. Higher circulating acylcarnitne abundances with increased inflammation and risk of cardiovascular disease [34][35][36]. Physiologically, acyl carnitines function in mitochondrial metabolism of fatty acids, the removal of excess acyl groups from the body, and the modulation of intracellular coenzyme A homeostasis [37].…”

Section: Discussionmentioning

confidence: 99%

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Metabolomic Profiling Reveals Sex Specific Associations with Chronic Obstructive Pulmonary Disease and Emphysema

et al. 2021

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Susceptibility and progression of lung disease, as well as response to treatment, often differ by sex, yet the metabolic mechanisms driving these sex-specific differences are still poorly understood. Women with chronic obstructive pulmonary disease (COPD) have less emphysema and more small airway disease on average than men, though these differences become less pronounced with more severe airflow limitation. While small studies of targeted metabolites have identified compounds differing by sex and COPD status, the sex-specific effect of COPD on systemic metabolism has yet to be interrogated. Significant sex differences were observed in 9 of the 11 modules identified in COPDGene. Sex-specific associations by COPD status and emphysema were observed in 3 modules for each phenotype. Sex stratified individual metabolite associations with COPD demonstrated male-specific associations in sphingomyelins and female-specific associations in acyl carnitines and phosphatidylethanolamines. There was high preservation of module assignments in SPIROMICS (SubPopulations and InteRmediate Outcome Measures In COPD Study) and similar female-specific shift in acyl carnitines. Several COPD associated metabolites differed by sex. Acyl carnitines and sphingomyelins demonstrate sex-specific abundances and may represent important metabolic signatures of sex differences in COPD. Accurately characterizing the sex-specific molecular differences in COPD is vital for personalized diagnostics and therapeutics.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Metabolomic Profiling Reveals Sex Specific Associations with Chronic Obstructive Pulmonary Disease and Emphysema

et al. 2021

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“…В другом исследовании 74 пациентов с ишемической болезнью сердца обнаружена отрицательная корреляция уровня сфингозин-1-фосфата и сфингомиелина с величиной фракции выброса ЛЖ [44]. Наше исследование продемонстрировало значимую ассоциацию уровня циркулирующих ацилкарнитинов со степенью гипертрофии миокарда и параметрами диастолической дисфункции [45].…”

Section: метаболомикаunclassified

Biomarkers in Heart Failure: Current and Future

Kozhevnikova

Belenkov

2021

Kardiologiia

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Heart failure (HF) is the ending of practically all cardiovascular diseases and the reason for hospitalization of 49% of patients in a cardiological hospital. Available instrumental diagnostic methods and biomarkers not always allow verification of HF, particularly in patients with preserved left ventricular ejection fraction. Prediction of chronic HF in patients with risk factors faces great difficulties. Currently, natriuretic peptides (NUP) are widely used for the diagnosis, prognosis and management of patients with HF and are included in clinical guidelines for diagnosis and treatment of HF. Following multiple studies, the understanding of NUP significance has changed. This resulted in a need for new biomarkers to improve the insight into the process of HF and to personalize the treatment by better individual phenotyping. In addition, current technologies, such as transcriptomic, proteomic and metabolomic analyses, provide identification of new biomarkers and better understanding of features of the HF pathogenesis. The aim of this study was to discuss recent reports on NUP and novel, most promising biomarkers in respect of their possible use in clinical practice.

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“…Recently, acylcarnitines have been suggested as potential biomarkers of cardiometabolic diseases ( 9 ). Specifically, elevated acylcarnitines levels were observed in patients with type 2 diabetes ( 10 , 11 ), heart failure ( 12 – 14 ), and in middle-aged adults and elderly with a combination of different cardiovascular diseases ( 15 , 16 ). Additionally, circulating acylcarnitines were associated with the risk of myocardial infarction and cardiovascular death in individuals with stable angina pectoris ( 17 ) as well as with the risk of cardiovascular events at 3-year follow-up in patients with CAD ( 18 , 19 ).…”

Section: Introductionmentioning

confidence: 99%

“…Similarly, elevated serum concentration of branched-chain amino acids (BCAAs), whose metabolism is tightly related to that of short-chain acylcarnitines, was observed in patients with insulin resistance ( 20 – 22 ), obesity ( 23 , 24 ), diabetes ( 25 – 27 ), dyslipidemia, and CAD ( 19 , 28 , 29 ). These studies, however, investigated patients already suffering from cardiometabolic diseases without including healthy controls ( 12 , 13 , 15 , 17 – 19 , 23 – 28 ) or with poorly characterized controls ( 14 , 16 , 20 , 22 , 29 ). Comparing diseased against healthy metabolic signature is essential to reveal disease-associated alterations and to improve our understanding of metabolites' roles in pathophysiological processes ( 30 , 31 ).…”

Section: Introductionmentioning

confidence: 99%

Metabolic Impairment in Coronary Artery Disease: Elevated Serum Acylcarnitines Under the Spotlights

Gander

Carrard

Gallart-Ayala

et al. 2021

Front. Cardiovasc. Med.

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Coronary artery disease (CAD) remains the leading cause of death worldwide. Expanding patients' metabolic phenotyping beyond clinical chemistry investigations could lead to earlier recognition of disease onset and better prevention strategies. Additionally, metabolic phenotyping, at the molecular species level, contributes to unravel the roles of metabolites in disease development. In this cross-sectional study, we investigated clinically healthy individuals (n = 116, 65% male, 70.8 ± 8.7 years) and patients with CAD (n = 54, 91% male, 67.0 ± 11.5 years) of the COmPLETE study. We applied a high-coverage quantitative liquid chromatography-mass spectrometry approach to acquire a comprehensive profile of serum acylcarnitines, free carnitine and branched-chain amino acids (BCAAs), as markers of mitochondrial health and energy homeostasis. Multivariable linear regression analyses, adjusted for confounders, were conducted to assess associations between metabolites and CAD phenotype. In total, 20 short-, medium- and long-chain acylcarnitine species, along with L-carnitine, valine and isoleucine were found to be significantly (adjusted p ≤ 0.05) and positively associated with CAD. For 17 acylcarnitine species, associations became stronger as the number of affected coronary arteries increased. This implies that circulating acylcarnitine levels reflect CAD severity and might play a role in future patients' stratification strategies. Altogether, CAD is characterized by elevated serum acylcarnitine and BCAA levels, which indicates mitochondrial imbalance between fatty acid and glucose oxidation.

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Relationship between the plasma acylcarnitine profile and cardiometabolic risk factors in adults diagnosed with cardiovascular diseases

Cited by 26 publications

References 29 publications

Metabolomic Profiling Reveals Sex Specific Associations with Chronic Obstructive Pulmonary Disease and Emphysema

Metabolomic Profiling Reveals Sex Specific Associations with Chronic Obstructive Pulmonary Disease and Emphysema

Biomarkers in Heart Failure: Current and Future

Metabolic Impairment in Coronary Artery Disease: Elevated Serum Acylcarnitines Under the Spotlights

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