Qualitative and Quantitative Effects of Fatty Acids Involved in Heart Diseases

Moriyama, Hidenori; Endo, Jin; Ikura, Hidehiko; Kitakata, Hiroki; Momoi, Mizuki; Shinya, Yoshiki; Ko, Seien; Ichihara, Genki; Hiraide, Takahiro; Shirakawa, Kohsuke; Anzai, Atsushi; Katsumata, Yoshinori; Sano, Motoaki

doi:10.3390/metabo12030210

Cited by 9 publications

(6 citation statements)

References 129 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In particular, increased β-oxidation of fatty acids can be detrimental, as it requires more oxygen and generates a large amount of ROS. Interestingly, diabetic animals showed reduced cardiac efficiency, with increased myocardial oxygen consumption (VO2) associated with increased fatty acid β-oxidation [53][54][55][56][57][58][59]. The increased demand for oxidant fatty acids and reduced cardiac efficiency may contribute to contractile dysfunction in the diabetic heart.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial-derived Peptide Single-nucleotide Polymorphisms Associated with Cardiovascular Complications in Type 2 Diabetes

Gaona¹,

Gregorio²,

Jiménez³

et al. 2022

Preprint

View full text Add to dashboard Cite

Since the discovery of mitochondrial-derived peptides (MDP), their participation in cellular metabolism is no longer considered as the sole function of the mitochondria, but importance was also attached to its role as a source of protective factors of metabolic stress. These peptides are encoded in the mitochondrial genome and translated into the mitochondria or cytoplasm, to signal within the cell or be released and bind to membrane receptors. The objective of this work was explored and compare the frequency of MT-RNR1 and MT-RNR2 variants in sequences obtained from T2D individuals and control population. 213 different mitochondrial polymorphisms previously reported in the literature associated with T2D and cardiovascular diseases were analyzed. We can found three variants in the MT-RNR1 not related with MOTS-c coding sequence: m.1189T>C (rs28358571), m.1420T>C (rs111033356), and m.1438A>G (rs2001030); and secondly, three polymorphisms associated to MT-RNR2 m.2667T>C (rs878870626) related to humanin, m.1811A>G (rs28358576) in SHPL3 and m.3027T>C (rs199838004) in SHPL6 associated with statistical differences between the T2D and control group. All these findings were previously related to cardiovascular complications in literature and, as far as we know, relating for the first time in diabetic patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Mitochondrial-derived Peptide Single-nucleotide Polymorphisms Associated with Cardiovascular Complications in Type 2 Diabetes

Gaona¹,

Gregorio²,

Jiménez³

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…This is due to a relative supply/demand imbalance in the mitochondrial Coenzyme Q pool. 3,64 Our metabolomic analysis of cardiac tissues at the ischemic core confirmed the accumulation of succinate, followed by a decrease upon reoxygenation (Figure S2D). Intriguingly, these observations are inversely associated with the fluctuation of fumarate (Figures S1C and S2D).…”

Section: Glutathione Is Released Into Myocardial Extracellular Fluid ...mentioning

confidence: 67%

MRP1-Dependent Extracellular Release of Glutathione Induces Cardiomyocyte Ferroptosis After Ischemia-Reperfusion

Ichihara,

Katsumata,

Sugiura

et al. 2023

Circulation Research

Self Cite

View full text Add to dashboard Cite

Background: The membrane components of cardiomyocytes are rich in polyunsaturated fatty acids, which are easily oxidized. Thus, an efficient glutathione-based lipid redox system is essential for maintaining cellular functions. However, the relationship between disruption of the redox system during ischemia-reperfusion (IR), oxidized lipid production, and consequent cell death (ferroptosis) remains unclear. We investigated the mechanisms underlying the disruption of the glutathione-mediated reduction system related to ferroptosis during IR and developed intervention strategies to suppress ferroptosis. Methods: In vivo fluctuations of both intra- and extracellular metabolite levels during IR were explored via microdialysis and tissue metabolome analysis. Oxidized phosphatidylcholines were assessed using liquid chromatography high-resolution mass spectrometry. The areas at risk following IR were assessed using triphenyl-tetrazolium chloride/Evans blue stain. Results: Metabolomic analysis combined with microdialysis revealed a significant release of glutathione from the ischemic region into extracellular spaces during ischemia and after reperfusion. The release of glutathione into extracellular spaces and a concomitant decrease in intracellular glutathione concentrations were also observed during anoxia-reperfusion in an in vitro cardiomyocyte model. This extracellular glutathione release was prevented by chemical inhibition or genetic suppression of glutathione transporters, mainly MRP1 (multidrug resistance protein 1). Treatment with MRP1 inhibitor reduced the intracellular reactive oxygen species levels and lipid peroxidation, thereby inhibiting cell death. Subsequent in vivo evaluation of endogenously oxidized phospholipids following IR demonstrated the involvement of ferroptosis, as levels of multiple oxidized phosphatidylcholines were significantly elevated in the ischemic region 12 hours after reperfusion. Inhibition of the MRP1 transporter also alleviated intracellular glutathione depletion in vivo and significantly reduced the generation of oxidized phosphatidylcholines. Administration of MRP1 inhibitors significantly attenuated infarct size after IR injury. Conclusions: Glutathione was released continuously during IR, primarily in an MRP1-dependent manner, and induced ferroptosis. Suppression of glutathione release attenuated ferroptosis and reduced myocardial infarct size following IR.

show abstract

“…Mast cells resident in tissues are strongly affected by the local environment, exerting various functions in each tissue in various pathological conditions and playing unique roles. In addition, the development of lipidomics technology has enabled accurate measurement of fatty acid metabolites, and there are reports on how bioactive lipids and their producing enzymes are involved in various pathological conditions [ 112 ]. For intractable diseases including PH, the fundamental pathological mechanisms have not yet been elucidated, and effective therapeutic materials are lacking.…”

Section: Discussionmentioning

confidence: 99%

Pathophysiological Involvement of Mast Cells and the Lipid Mediators in Pulmonary Vascular Remodeling

Moriyama

Endo

2023

IJMS

Self Cite

View full text Add to dashboard Cite

Mast cells are responsible for IgE-dependent allergic responses, but they also produce various bioactive mediators and contribute to the pathogenesis of various cardiovascular diseases, including pulmonary hypertension (PH). The importance of lipid mediators in the pathogenesis of PH has become evident in recent years, as exemplified by prostaglandin I2, the most central therapeutic target in pulmonary arterial hypertension. New bioactive lipids other than eicosanoids have also been identified that are associated with the pathogenesis of PH. However, it remains largely unknown how mast cell-derived lipid mediators are involved in pulmonary vascular remodeling. Recently, it has been demonstrated that mast cells produce epoxidized n-3 fatty acid (n-3 epoxides) in a degranulation-independent manner, and that n-3 epoxides produced by mast cells regulate the abnormal activation of pulmonary fibroblasts and suppress the progression of pulmonary vascular remodeling. This review summarizes the role of mast cells and bioactive lipids in the pathogenesis of PH. In addition, we introduce the pathophysiological role and therapeutic potential of n-3 epoxides, a mast cell-derived novel lipid mediator, in the pulmonary vascular remodeling in PH. Further knowledge of mast cells and lipid mediators is expected to lead to the development of innovative therapies targeting pulmonary vascular remodeling.

show abstract

Qualitative and Quantitative Effects of Fatty Acids Involved in Heart Diseases

Cited by 9 publications

References 129 publications

Mitochondrial-derived Peptide Single-nucleotide Polymorphisms Associated with Cardiovascular Complications in Type 2 Diabetes

Mitochondrial-derived Peptide Single-nucleotide Polymorphisms Associated with Cardiovascular Complications in Type 2 Diabetes

MRP1-Dependent Extracellular Release of Glutathione Induces Cardiomyocyte Ferroptosis After Ischemia-Reperfusion

Pathophysiological Involvement of Mast Cells and the Lipid Mediators in Pulmonary Vascular Remodeling

Contact Info

Product

Resources

About