Association of Plasma 7-Ketocholesterol With Cardiovascular Outcomes and Total Mortality in Patients With Coronary Artery Disease

Song, Jiayi; Chen, Hongen; Huang, Xiaorong; Yuan, Zuyi; Jiang, Nan; Chen, Chaogang; Xia, Min

doi:10.1161/circresaha.117.311049

Cited by 47 publications

(32 citation statements)

References 40 publications

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“…Previous studies have revealed that oxidative damage products, such as oxidized LDL and oxysterols, are found in patients with cardiovascular disease [30] , [31] . 7KCh is considered an important metabolite for monitoring cardiovascular disease outcomes and mortality [32] as well as for predicting the incidence of cardiovascular disease events in general population [33] . Accumulation of 7KCh in HF erythrocytes suggests that 7KCh is a risk factor for HF, with a potential for clinical applications.…”

Section: Discussionmentioning

confidence: 99%

Lipidomics reveals accumulation of the oxidized cholesterol in erythrocytes of heart failure patients

Tang

Wang

et al. 2018

Redox Biology

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Lipids play an important role in the pathogenesis of cardiovascular disease. Changes in lipids of erythrocytes are indicative of the outcome of pathophysiological processes. In the present study, we assessed whether the lipid profiles of erythrocytes from heart failure (HF) patients are informative of their disease risk. The lipidomes of erythrocytes from 10 control subjects and 29 patients at different HF stages were analyzed using liquid chromatography time-of-flight mass spectrometry. The lipid composition of erythrocytes obtained from HF patients was significantly different from that of normal controls. The levels of phosphatidylcholines (PCs), phosphatidylethanolamines (PEs), and sphingomyelins decreased in HF erythrocytes as compared with those of control subjects; however, the levels of lysoPCs, lysoPEs, and ceramides increased in HF erythrocytes. Notably, the oxidized cholesterol 7-ketocholesterol (7KCh) accumulated to higher level in HF erythrocytes than in plasma from the same patients. We further validated our findings with a cohort of 115 subjects of control subjects (n=28) and patients (n=87). Mechanistically, 7KCh promoted reactive oxygen species (ROS) formation in cardiomyocytes; and induced their death, probably through an ATF4-dependent pathway. Our findings suggest that erythrocytic 7KCh can be a risk factor for HF, and is probably implicated in its pathophysiology.

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Section: Discussionmentioning

confidence: 99%

Lipidomics reveals accumulation of the oxidized cholesterol in erythrocytes of heart failure patients

Tang

Wang

et al. 2018

Redox Biology

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“…We believe that this elevation is caused by the role of 7-KC (and possibly C-triol) in the formation of atherosclerotic plaque. Song et al (12) investigated 7-KC levels in 1016 patients and they noted that high 7-KC levels caused increased risk of cardiovascular disease, total mortality and increased morbidity of coronary artery disease. In our study, the post-test 7-KC levels were highest (39.87 ± 2.13 ng/mL) in the positive group and the lowest in the healthy group (20.26 ± 1.35 ng/mL).…”

Section: Discussionmentioning

confidence: 99%

“…Oxysterols have been implicated in the formation and progression of atherosclerotic plaques (6, 7). 7-ketocholesterol (7-KC), 7ß-hydroxycholesterol (7ß-OHC), beta-isomers of epoxide, 27-hydroxycholesterol (27-OHC) and cholestane-3β,5α,6β-triol (C-triol) have been shown to increase in plasma and/or atherosclerotic plaque in various studies (8, 9, 10, 11, 12). 7-KC occurs via the reaction of peroxyl and alkoxyl radicals and the Russell mechanism, and also can be converted from 7β-OHC by the enzyme 11β-hydroxysteroid dehydrogenase (13, 14).…”

Section: Introductionmentioning

confidence: 99%

The effect of effort test on the levels of ischemia modified albumin, 7-ketocholesterol and cholestan-3β , 5α , 6β -triol and their role in the diagnosis of coronary artery disease

Keles

Samadi

İşikhan

et al. 2019

Journal of Medical Biochemistry

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Summary Background Oxysterols have been shown to play a role in plaque formation while ischemia modified albumin (IMA) is widely accepted as an acute marker for ischemia. The effort test is one of the methods used to identify the presence of coronary artery disease. Thus, there may be a relationship between effort test result and the levels of IMA, 7-ketocholesterol (7-KC) and cholestane-3β,5α,6β-triol (C-triol). Methods Thirty patients who underwent effort test and 30 healthy subjects were included in the study. IMA levels were determined with the albumin-cobalt binding test, 7-KC and C-triol levels were determined with LC-MS/MS. Among the patients, two subgroups were identified according to the results of the effort test, group 1 consisted of patients with a positive effort test (n = 12), and group 2 consisted of patients who had a negative effort test (n = 18). Results 7-KC levels of patients were significantly higher compared to healthy subjects (39.87 ± 2.13 ng/mL, 20.26 ± 1.35 ng/mL; p=0.001). In patients, post-test 7-KC levels were significantly lower than pre-test levels (post-test vs. pre-test: 37.73 ± 2.44 ng/mL vs. 41.07 ± 2.18 ng/mL; p<0.001). There was a significant difference in post-test 7-KC levels among all study groups (negative, positive and healthy: 37.73 ± 2.44 ng/mL, 39.87 ± 2.13 ng/mL, 20.26 ± 1.35 ng/mL, respectively). There was no significant difference in IMA levels. Conclusions Patients with positive effort test had significantly higher levels of 7-KC. Additionally, after the effort test, the 7-KC value was reduced. 7-KC is a biomarker of oxidative damage and its value or changes before and after the effort test may be used as a biomarker in the diagnosis and follow-up of coronary artery disease.

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“…Indeed, the presence of these molecules has been confirmed in oxidized LDL, in the plasma of hypercholesterolemic subjects, and in atherosclerotic plaques of both animal and human origin . Of note, a very recent cohort study underlined an association between 7‐KC and the increased risk of cardiovascular events and total mortality, in patients with stable coronary artery disease …”

Section: Oxysterols As Pathological Bioactive Compounds: a Possible Lmentioning

confidence: 93%

Lipid Oxidation Derived Aldehydes and Oxysterols Between Health and Disease

Sottero

Leonarduzzi

Testa

et al. 2018

Euro J Lipid Sci & Tech

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Non‐enzymatic and enzymatic oxidation of lipids has long been a primary issue in human pathophysiology, with special emphasis on diet‐ and nutrition‐related aspects. While there is no doubt that the n‐3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid, and docosahexaenoic acid, exert anti‐inflammatory, inflammation resolving, and immunomodulatory effects in different model systems, their non‐enzymatic oxidation during food storage and cooking, as well as during gastrointestinal digestion, can give rise to excessive amounts of quite reactive aldehydic end‐products, in particular 4‐hydroxyhexenal. However, the non‐enzymatic oxidation of n‐6 PUFAs is, in principle, far more harmful, not least because one of its main end‐products, 4‐hydroxynonenal, has been shown to be associated with the progression of a number of human diseases. Several cholesterol oxidation products, known as oxysterols, are also of primary nutritional importance; these can be generated in the human body through both enzymatic and non‐enzymatic reactions, but may also be present in the diet in excessive amounts due to the autoxidation of cholesterol‐containing foods. Their potential contribution to the pathogenesis and progression of human diseases in which hypercholesterolemia is a primary risk factor, such as atheroclerosis, Alzheimer's disease, and some forms of cancers, has been unanimously recognized. Practical Applications: This review highlights the importance of certain lipid oxidation products, namely 4‐hydroxyalkenals and oxysterols, in the modulation of processes fundamental to human health and disease. The observations and facts reviewed here underline the need to carefully consider the pros and cons of the dietary intake and metabolic fate of n‐3 PUFA, n‐6 PUFA, and cholesterol, when producing, storing, and processing lipid‐containing food. Lipid oxidation is a common process that occurs through both enzymatic and non‐enzymatic reactions. It is responsible for the formation of several compounds, including polyunsaturated fatty acid (PUFA)‐derived 4‐hydroxyalkenals and cholesterol oxidation products, namely oxysterols. Depending on their concentrations, these molecules possess physiopathological properties involved in cell viability and function. At high concentrations, such as those resulting from intense oxidative stress or excessive fatty food intake, they are associated to the onset of many diseases. A correct diet regimen, improved food processing and storage, and suitable antioxidant supplementation, should be implemented to counteract promotion of disease development by excess oxidized lipids. (HHE, 4‐hydroxyhexenal; HNE, 4‐hydroxynonenal; ROS, reactive oxygen species).

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Association of Plasma 7-Ketocholesterol With Cardiovascular Outcomes and Total Mortality in Patients With Coronary Artery Disease

Abstract: High 7-KC levels are associated with increased risk of cardiovascular events, total death, and composite outcomes in patients with stable coronary artery disease.

Cited by 47 publications

References 40 publications

Lipidomics reveals accumulation of the oxidized cholesterol in erythrocytes of heart failure patients

Lipidomics reveals accumulation of the oxidized cholesterol in erythrocytes of heart failure patients

The effect of effort test on the levels of ischemia modified albumin, 7-ketocholesterol and cholestan-3β , 5α , 6β -triol and their role in the diagnosis of coronary artery disease

Lipid Oxidation Derived Aldehydes and Oxysterols Between Health and Disease

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