Sphingolipid Mediators of Myocardial Pathology

Kovilakath, Anna; Cowart, L. Ashley

doi:10.12997/jla.2020.9.1.23

Cited by 18 publications

(19 citation statements)

References 212 publications

(244 reference statements)

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“…Sphingolipids regulated many cellular processes that occurred in primary and secondary cardiomyopathy, and were also involved in functional categories and pathways, such as “Glycosphingolipid biosynthesis”, “Sphingolipid metabolism” and “sphingolipid metabolic process “. And a large number of studies have shown that disorders of sphingolipid metabolism can cause changes in the structure and function of cardiomyocytes [ 21 – 23 ].…”

Section: Resultsmentioning

confidence: 99%

Identification of cardiomyopathy-related core genes through human metabolic networks and expression data

et al. 2022

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Background Cardiomyopathy is a complex type of myocardial disease, and its incidence has increased significantly in recent years. Dilated cardiomyopathy (DCM) and ischemic cardiomyopathy (ICM) are two common and indistinguishable types of cardiomyopathy. Results Here, a systematic multi-omics integration approach was proposed to identify cardiomyopathy-related core genes that could distinguish normal, DCM and ICM samples using cardiomyopathy expression profile data based on a human metabolic network. First, according to the differentially expressed genes between different states (DCM/ICM and normal, or DCM and ICM) of samples, three sets of initial modules were obtained from the human metabolic network. Two permutation tests were used to evaluate the significance of the Pearson correlation coefficient difference score of the initial modules, and three candidate modules were screened out. Then, a cardiomyopathy risk module that was significantly related to DCM and ICM was determined according to the significance of the module score based on Markov random field. Finally, based on the shortest path between cardiomyopathy known genes, 13 core genes related to cardiomyopathy were identified. These core genes were enriched in pathways and functions significantly related to cardiomyopathy and could distinguish between samples of different states. Conclusion The identified core genes might serve as potential biomarkers of cardiomyopathy. This research will contribute to identifying potential biomarkers of cardiomyopathy and to distinguishing different types of cardiomyopathy.

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Section: Resultsmentioning

confidence: 99%

Identification of cardiomyopathy-related core genes through human metabolic networks and expression data

et al. 2022

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“…It is reported that circulating Cer 18:1; O2/24:1, and Cer 18:1; O2/24:0 are associated with the risk of the incidence of major adverse cardiovascular events in healthy people ( 61 ). In the context of cardiomyopathy, increased ceramide levels or changes in ceramide compositions have been suggested to be toxic ( 62 ). The increased levels of SM and Cer were displayed in different type of cardiomyopathies ( 59 , 62 ).…”

Section: Discussionmentioning

confidence: 99%

“…In the context of cardiomyopathy, increased ceramide levels or changes in ceramide compositions have been suggested to be toxic ( 62 ). The increased levels of SM and Cer were displayed in different type of cardiomyopathies ( 59 , 62 ). To date, no sphingolipids studies have been associated with TTS in patient's serum.…”

Section: Discussionmentioning

confidence: 99%

Quantitative Lipidomic Analysis of Takotsubo Syndrome Patients' Serum

Karnati

Guntaş

Rajendran

et al. 2022

Front. Cardiovasc. Med.

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Takotsubo syndrome (TTS), also known as the transient left ventricular apical ballooning syndrome, is in contemporary times known as novel acute cardiac syndrome. It is characterized by transient left ventricular apical akinesis and hyperkinesis of the basal left ventricular portions. Although the precise etiology of TTS is unknown, events like the sudden release of stress hormones, such as the catecholamines and the increased inflammatory status might be plausible causes leading to the cardiovascular pathologies. Recent studies have highlighted that an imbalance in lipid accumulation might promote a deviant immune response as observed in TTS. However, there is no information on comprehensive profiling of serum lipids of TTS patients. Therefore, we investigated a detailed quantitative lipid analysis of TTS patients using ES-MSI. Our results showed significant differences in the majority of lipid species composition in the TTS patients compared to the control group. Furthermore, the computational analyses presented was able to link the altered lipids to the pro-inflammatory cytokines and disseminate possible mechanistic pathways involving TNFα and IL-6. Taken together, our study provides an extensive quantitative lipidome of TTS patients, which may provide a valuable Pre-diagnostic tool. This would facilitate the elucidation of the underlying mechanisms of the disease and to prevent the development of TTS in the future.

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“…Ceramide accumulation was proposed to mediate cardiomyocyte apoptosis induced by ischemia-reperfusion, TNF-α, and palmitate in several rodent models of obesity and diabetes, including the ZDF rats, db/db, and ob/ob mice. 96,156 It has also been shown that cardiomyocyte apoptosis in individuals with obesity and diabetes, as compared to lean individuals, is accompanied by elevated expression of neutral sphingomyelinase and serine palmitoyltransferase, emphasizing the potential role of altered ceramide metabolism in cardiac failure in patients with obesity, with and without T2D (Figure 4). 55 What is the mechanism that underlies these alterations in sphingolipid metabolism?…”

Section: Obesity T2d and Associated Inflammatory Conditionsmentioning

confidence: 98%

Neutral sphingomyelinase‐2 and cardiometabolic diseases

et al. 2021

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Sphingolipids, in particular ceramides, play vital role in pathophysiological processes linked to metabolic syndrome, with implications in the development of insulin resistance, pancreatic ß-cell dysfunction, type 2 diabetes, atherosclerosis, inflammation, nonalcoholic steatohepatitis, and cancer. Ceramides are produced by the hydrolysis of sphingomyelin, catalyzed by different sphingomyelinases, including neutral sphingomyelinase 2 (nSMase2), whose dysregulation appears to underlie many of the inflammation-related pathologies. In this review, we discuss the current knowledge on the biochemistry of nSMase2 and ceramide production and its regulation by inflammatory cytokines, with particular reference to cardiometabolic diseases. nSMase2 contribution to pathogenic processes appears to involve cyclical feedforward interaction with proinflammatory cytokines, such as TNF-α and IL-1ß, which activate nSMase2 and the production of ceramides, that in turn triggers the synthesis and release of inflammatory cytokines. We elaborate these pathogenic interactions at the molecular level and discuss the potential therapeutic benefits of inhibiting nSMase2 against inflammation-driven cardiometabolic diseases.

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Sphingolipid Mediators of Myocardial Pathology

Cited by 18 publications

References 212 publications

Identification of cardiomyopathy-related core genes through human metabolic networks and expression data

Identification of cardiomyopathy-related core genes through human metabolic networks and expression data

Quantitative Lipidomic Analysis of Takotsubo Syndrome Patients' Serum

Neutral sphingomyelinase‐2 and cardiometabolic diseases

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