Elevated levels of oxidized low-density lipoprotein and impaired nocturnal synthesis of melatonin in patients with myocardial infarction

Domínguez‐Rodríguez, Alberto; Abreu-González, Pedro; García-González, Martín J.; Ferrer-Hita, Julio J.; Vargas, Manuel; Reíter, Russel J.

doi:10.1016/j.atherosclerosis.2004.11.003

Cited by 61 publications

(37 citation statements)

References 38 publications

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“…In vitro studies have given evidence for antioxidant actions of melatonin on LDL-C oxidation [57]. In keeping with this, Dominguez-Rodriguez et al [58] reported a relationship between nocturnally elevated oxidized serum LDL-C and reduced circulating melatonin levels in patients with acute myocardial infarction. Hence, treatment with melatonin reduces blood pressure in rodents [59] and humans [55, 60].…”

Section: Tryptophan Metabolism and Melatonin: Specific Links To Cardimentioning

confidence: 91%

Disturbed Tryptophan Metabolism in Cardiovascular Disease

Mangge

Stelzer²,

Reininghaus³

et al. 2014

CMC

103

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Atherosclerosis (AS), a major pathologic consequence of obesity, is the main etiological factor of cardiovascular disease (CVD), which is the most common cause of death in the western world. A systemic chronic low grade immune-mediated inflammation (scLGI) is substantially implicated in AS and its consequences. In particular, pro-inflammatory cytokines play a major role, with Th1-type cytokine interferon-γ (IFN-γ) being a key mediator. Among various other molecular and cellular effects, IFN- γ activates the enzyme indoleamine 2,3-dioxygenase (IDO) in monocyte-derived macrophages, dendritic, and other cells, which, in turn, decreases serum levels of the essential amino acid tryptophan (TRP). Thus, people with CVD often have increased serum kynurenine to tryptophan ratios (KYN/TRP), a result of an increased TRP breakdown. Importantly, increased KYN/TRP is associated with a higher likelihood of fatal cardiovascular events. A scLGI with increased production of the proinflammatory adipokine leptin, in combination with IFN-γ and interleukin-6 (IL-6), represents another central link between obesity, AS, and CVD. Leptin has also been shown to contribute to Th1-type immunity shifting, with abdominal fat being thus a direct contributor to KYN/TRP ratio. However, TRP is not only an important source for protein production but also for the generation of one of the most important neurotransmitters, 5-hydroxytryptamine (serotonin), by the tetrahydrobiopterin-dependent TRP 5-hydroxylase. In prolonged states of scLGI, availability of free serum TRP is strongly diminished, affecting serotonin synthesis, particularly in the brain. Additionally, accumulation of neurotoxic KYN metabolites such as quinolinic acid produced by microglia, can contribute to the development of depression via NMDA glutamatergic stimulation. Depression had been reported to be associated with CVD endpoints, but it most likely represents only a secondary loop connecting excess adipose tissue, scLGI and cardiovascular morbidity and mortality. Accelerated catabolism of TRP is further involved in the pathogenesis of the anemia of scLGI. The pro-inflammatory cytokine IFN-γ suppresses growth and differentiation of erythroid progenitor cells, and the depletion of TRP limits protein synthesis and thus hemoglobin production, and, through reduction in oxygen supply, may contribute to ischemic vascular disease. In this review we discuss the impact of TRP breakdown and the related complex mechanisms on the prognosis and individual course of CVD. Measurement of TRP, KYN concentrations, and calculation of the KYN/TRYP ratio will contribute to a better understanding of the interplay between inflammation, metabolic syndrome, mood disturbance, and anemia, all previously described as significant predictors of an unfavorable outcome in patients with CVD. The review leads to a novel framework for successful therapeutic modification of several cardinal pathophysiological processes leading to adverse cardiovascular outcome.

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Section: Tryptophan Metabolism and Melatonin: Specific Links To Cardimentioning

confidence: 91%

Disturbed Tryptophan Metabolism in Cardiovascular Disease

Mangge

Stelzer²,

Reininghaus³

et al. 2014

CMC

103

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“…Multiple biological factors have been postulated as contributing to these circadian rhythms, including cyclic patterns in heart rate 9 ; QT interval dispersion 10 -12 ; hemostasis [13][14][15] ; platelet aggregation 13,16 ; lipoprotein levels 17,18 ; hormonal levels 2 ; and sympathetic tone, particularly on awakening. 19 In addition, early morning hours often represent the nadir levels of once-a-day morning dosing of cardioprotective medications.…”

mentioning

confidence: 99%

Circadian Rhythms in Patients With ST-Elevation Myocardial Infarction

Holmes

Aguirre

Aplin

et al. 2010

Circ: Cardiovascular Quality and Outcomes

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“…The degree of oxidation of LDL particles would probably be a better index of the effect of melatonin than lipid concentrations. 85,90,91 Further, it is likely that only very high supraphysiological doses of melatonin could demonstrate an antioxidant effect in vivo.…”

Section: Effect Of Melatonin On Lipidsmentioning

confidence: 99%

“…93 In 24 patients suffering from multiple sclerosis, a subgroup with low levels of nocturnal plasma melatonin had higher serum total cholesterol concentrations than those in a subgroup with normal plasma melatonin levels. 94 In 60 patients with acute myocardial infarction 90 and in 21 patients suffering from unstable angina, 91 night-time melatonin levels were decreased compared with controls and associated with elevated oxidized serum LDL levels. The latter and similar studies (reviewed in DominguezRodriguez et al) 95 triggered the design of two clinical studies of the efficacy of intravascular injections of melatonin during angioplasty for limitation of ischemia-reperfusion injury in patients with acute myocardial infarction (http://www.…”

mentioning

confidence: 98%

Melatonin and its use in atherosclerosis and dyslipidemia

Danilenko¹,

Ragino²

2013

CPT

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A review of pineal melatonin synthesis, regulation, and physiological effects indicates that not only does melatonin act as a hormonal signal of darkness, but also that it possesses antioxidant and anti-inflammatory properties. Although oxidation and inflammation play a pivotal role in atherogenesis, no studies have investigated administration of melatonin for human arterial atherosclerosis. However, 13 clinical trials have investigated use of melatonin in dyslipidemia, which is a close correlate of atherosclerosis. The results of these clinical trials, particularly the five that are placebo-controlled, are inconclusive as to whether melatonin can normalize the blood lipid profile. Significant confounders in these studies might be a phase shift of the cholesterol rhythm by melatonin, a posture effect at venipuncture, uncontrolled diet during the course of melatonin intake, and the phenomenon of regression to the mean. Thus, future studies are required, which should also consider use of higher doses of melatonin and/or measurement of oxidized forms of cholesterol-containing particles (which are the most aggressive in relation to atherogenesis) in addition to lipidic fractions.

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Elevated levels of oxidized low-density lipoprotein and impaired nocturnal synthesis of melatonin in patients with myocardial infarction

Cited by 61 publications

References 38 publications

Disturbed Tryptophan Metabolism in Cardiovascular Disease

Disturbed Tryptophan Metabolism in Cardiovascular Disease

Circadian Rhythms in Patients With ST-Elevation Myocardial Infarction

Melatonin and its use in atherosclerosis and dyslipidemia

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