Lipid-membrane interactions and the pathogenesis of ischemic damage in the myocardium.

Katz, Arnold M.; Messineo, Frank C.

doi:10.1161/01.res.48.1.1

Cited by 561 publications

(183 citation statements)

References 190 publications

Supporting

Mentioning

174

Contrasting

Order By: Relevance

“…Furthermore, catecholamine stimulation during myocardial ischemia increases the concentration of circulating FFAs as a result of lipolysis with the breakdown of triglycerides into FFAs and glycerol by catecholamine‐sensitive lipase in adipose tissue 38, 39. The ischemic myocardium is exposed to hypoxia due to excessive oxygen consumption during FFA metabolism, which reduces the myocardial uptake of glucose that is required for anaerobic glycolysis and mitochondrial ATP production 40, 41, 42. The excessive uptake of FFAs into myocardium contributes to cardiac function impairment in the ischemic process, which can subsequently increase infarct size and mortality 38, 43…”

Section: Discussionmentioning

confidence: 99%

Deletion of Apoptosis Inhibitor of Macrophage (AIM)/CD5L Attenuates the Inflammatory Response and Infarct Size in Acute Myocardial Infarction

Nishikido

Oyama

Shiraki

et al. 2016

JAHA

View full text Add to dashboard Cite

BackgroundAn excessive inflammatory response after myocardial infarction (MI) increases myocardial injury. The toll‐like receptor (TLR)‐4 is activated by the recognition of endogenous ligands and is proinflammatory when there is myocardial tissue injury. The apoptosis inhibitor of the macrophage (AIM) is known to provoke an efflux of saturated free fatty acids (FFA) due to lipolysis, which causes inflammation via the TLR‐4 pathway. Therefore, this study investigated the hypothesis that AIM causes a proinflammatory response after MI.Methods and ResultsThe left anterior descending coronary artery was ligated to induce MI in both AIM‐knockout (AIM−/−) and wild‐type (WT) mice. After 3 days, the inflammatory response from activation of the TLR‐4/NFκB pathway was assessed, and infarct size was measured by staining with triphenyltetrazolium chloride. In addition, left ventricular remodeling was examined after 28 days. Although the area at risk was similar between AIM−/− and WT mice, the infarct size was significantly smaller in AIM−/− mice (P=0.02). The heart weight–to–body weight ratio and myocardial fibrosis were also decreased in the AIM−/− mice, and the 28‐day survival rate was improved (P<0.01). With the reduction of plasma FFA in AIM−/− mice, myocardial IRAK4 and NFκB activity were decreased (all P<0.05). Moreover, there was a reduction in myeloperoxidase activity and inducible nitric oxide synthase as part of the inflammatory response (P<0.01, P=0.03, respectively). Furthermore, NFκB DNA‐binding activation via TLR‐4, neutrophil infiltration, and inflammatory mediators were decreased in AIM−/− mice.ConclusionsThe deletion of AIM reduced the inflammatory response and infarct size and improved survival after myocardial infarction.

show abstract

Section: Discussionmentioning

confidence: 99%

Deletion of Apoptosis Inhibitor of Macrophage (AIM)/CD5L Attenuates the Inflammatory Response and Infarct Size in Acute Myocardial Infarction

Nishikido

Oyama

Shiraki

et al. 2016

JAHA

View full text Add to dashboard Cite

show abstract

“…The glial cells that were im mediately damaged after exposure to AA might have been furnished with a lower endogenous de fense capability, for example, antioxidants against AA and its metabolites. Their abrupt decrease in cell size following the prompt intensive swelling re sponse at high AA concentrations (see previously) might be explained by severe membrane damage secondary to the formation of lipid micelles causing incorporation of fragments of the cell membrane (Katz and Messineo, 1981). The cell surface area and consequently cell volume might be reduced thereby.…”

Section: In Vitro Modelmentioning

confidence: 92%

“…More over, amphophilic lipids like AA have detergent properties at high concentrations, facilitating aggre gation into micelles. Such micelles have consider able damaging potential by incorporating membrane lipids from intact cells (Katz and Messineo, 1981).…”

Section: In Vitro Modelmentioning

confidence: 99%

Swelling, Acidosis, and Irreversible Damage of Glial Cells from Exposure to Arachidonic Acid in vitro

Staub¹,

Winkler²,

Peters³

et al. 1994

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

Swelling and damage of C6 glioma cells and of primary cultured astrocytes were analyzed in vitro during incubation with arachidonic acid (AA; 20:4). The cells were suspended in a physiological medium supplemented with AA at concentrations of 0.001–1.0 m M. Cell swelling was quantified by flow cytometry with hydrodynamic focusing. Flow cytometry was also utilized for assessment of cell viability by exclusion of the fluorescent dye propidium iodide and for measurement of the intracellular pH (pHi) by 2′,7′-bis-(2-carboxyethyl)−5(and −6)carboxyfluorescein. Administration of AA caused an immediate dose-dependent swelling of C6 glioma cells, even at a concentration of 0.01 m M. At this level cell volume increased within 20 min to 105.0% of control, at 0.1 m M to 111.0%, while at 1.0 m M to 123.7%. Following a phase of rapid cell volume increase, swelling leveled off during the subsequent observation period of 70 min. Viability of the C6 glioma cells was 90% under control conditions. It remained unchanged after raising AA concentrations to 0.1 m M. At 0.5 m M, however, cell viability fell to 72.8%, and at 1.0 m M to 32.7%. pHi of the glioma cells was 7.3 under control conditions. In parallel with the early swelling phase, AA led to a dose-dependent decrease of the intracellular pH and an elevated lactate production of the cells. During incubation with 0.1 m M AA, pHi decreased to 7.06 after 5 min, but recovered to normal subsequently. In addition, swelling-inducing properties of linoleic (18:2) or stearic (18:0) acid were analyzed for evaluation of the specificity of glial swelling induced by AA. Whereas stearic acid (0.1 m M) failed to induce a swelling response, linoleic acid (0.1 m M) was found to be effective. The volume increase of the glial cells, however, was only half of that found during exposure to AA at the same concentration. Further, glial swelling from AA or linoleic acid was completely inhibited by the aminosteroid U-74389F, an antagonist of lipid peroxidation. Finally, omission of Na+ ions in the suspension medium with replacement by choline led also to inhibition of the cell volume increase by AA. Experiments using astrocytes from primary culture confirmed the swelling-inducing properties of AA at a quantitative level, whereas vulnerability of the cells to AA was increased. The present results demonstrate an important role of AA in cytotoxic swelling and irreversible damage of glial cells at concentrations that occur in vivo in cerebral ischemia or trauma. The damaging potential of AA might be enhanced by a concurrently evolving intracellular acidosis, stimulating the formation of oxygen-derived free radicals and lipid peroxidation.

show abstract

“…Lowering of phospholipids, especially lecithin, in serum as well as deviations in fatty acid composition of phospholipids may, like other factors, promote cholesterol precipitation and atherosclerosis development and progression (8,9). It has been suggested, too, that phospholipid depletion plays a crucial role in increased membrane permeability to calcium inf1ux (32), while phosphatidyl serine promotes calcium binding to sarcolernna (33). The cholesteroVphospholipid ratio, the cholesterol concentration as well as fatty acid composition of phospholipids have been demonstrated to influence membrane fluidity.…”

Section: Pteridineslvol 11 Rnomentioning

confidence: 99%

Impairment of Lipid Metabolism Due to Deficiency of Pyridoxal-5-phosphate and/or Activated Immune system: its Interpretation

Rudzite¹,

Jurika²,

Jäger

et al. 2000

Pteridines

View full text Add to dashboard Cite

Impairment of lipid metabolism due to excess metabolite accumulation induced by pyridoxal-5-phosphate (P-5-P)-deficiency andlor stimulated immune system has been studied and interpreted. Decreased amounts of phospholipids as well as deviations in phospholipid classes and fatty acid composition of phospholipids have been demonstrated due to kynurenine accumulation in the blood of P-5-P-deficient cardiovascular patients and white rats as well as in cardiovascular patients with activated immune system identified by an increased neopterin concentration in the blood (dilated cardiomyopathy) . The addition of P-5-P to the incubation medium for phospholipid biosynthesis in vitro did not change fatty acid incorporation into phospholipids, whereas it normalised fatty acid incorporation into phospholipids in liYer homogenates recei,·ed from P-5-P-deficient rats: 'Ine addition of kynurenine, neopterin and noradrenalin (accumulated m isolated heart tissue after addition of kynurenine and neopterin to incubation medium for isolated heart) to incubation medium for phospholipid biosynthesis in vitro induced an increase of saturated and a decrease of polyunsaturated fatty acid incorporation into phospholipids. These changes in fatty acid incorporation into phospholipids were followed by increased cholesterol concentrations in samples and an increased cholesterol/phospholipid ratio. Our results suggest that these changes in lipids are characteristic for decreased membrane fluidity, depressed cell cycle and lowered possibility of phospholipids to keep cholesterol in solution. P-5-P-deficiency is also accompanied with excess accumulation of homocysteine in the blood. The addition of L-homocysteine to the incubation medium for phospholipid biosynthesis in vitro was followed by inverse changes in fatty acid incorporation into phospholipids when compared with kynurenine , neopterin and noradrenalin. L-homocysteine induced a decrease of saturated and an increase of polyunsaturated fatty acid incorporation into phospholipids. The cholesterol concentration decreased in samples and the cholesterol/phospholipid ratio decreased, too . These findings suggest that changes in lipids induced by L-homocysteine are characteristic for increased membrane fluidity and stimulated cell cycle. In this study, we have observed a similar effect to L-homocysteine effect when L-homocysteine, L-tryptophan and 5,6,7,8-tetrahydrobiopterin were added to the incubation medium for phospholipid biosynthesis in vitro. The comparison of our results with data from the literature allows to suggest that excess metabolite accumulation due to activated formation and inactivated catabolism of it plays a significant role in quantitative and qualitative changes of lipids, especially phospholipids, and therefore participates in the regulation of membrane fluidity, cell cycle of normal and malignant cells as well as in keeping cholesterol in the state of solution.

show abstract

Lipid-membrane interactions and the pathogenesis of ischemic damage in the myocardium.

Cited by 561 publications

References 190 publications

Deletion of Apoptosis Inhibitor of Macrophage (AIM)/CD5L Attenuates the Inflammatory Response and Infarct Size in Acute Myocardial Infarction

Deletion of Apoptosis Inhibitor of Macrophage (AIM)/CD5L Attenuates the Inflammatory Response and Infarct Size in Acute Myocardial Infarction

Swelling, Acidosis, and Irreversible Damage of Glial Cells from Exposure to Arachidonic Acid in vitro

Impairment of Lipid Metabolism Due to Deficiency of Pyridoxal-5-phosphate and/or Activated Immune system: its Interpretation

Contact Info

Product

Resources

About