The associations of plasma phospholipid arachidonic acid with cardiovascular diseases: A Mendelian randomization study

Zhang, Ting; Zhao, Jie; Schooling, CM

doi:10.1016/j.ebiom.2020.103189

Cited by 32 publications

(24 citation statements)

References 49 publications

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“…The oxidized lipid molecules participate in a variety of physiological and pathological functions. Upon binding to corresponding receptors and triggering the downstream signaling pathways in different tissues, AA metabolites play differential roles to control important cellular processes, such as cell apoptosis, cell proliferation, metabolism, and vascular function [ 7 , 13 ], and they are also related to many chronic diseases, especially cardiovascular diseases (CVD) [ 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

“…Despite the recent advances in drug and surgical treatment [ 19 ], CVD is still a common and progressive disease that threatens human health. Studies have shown that AA metabolites play an important role in cardiovascular health and disease mechanism, especially related to inflammation and atherosclerosis [ 15 ]. AA metabolites regulate the complex vascular functions in the human body and also play a role in the treatment of CVD.…”

Section: Introductionmentioning

confidence: 99%

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Effects of Arachidonic Acid Metabolites on Cardiovascular Health and Disease

Zhou¹,

Khan

Xiao

et al. 2021

IJMS

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Arachidonic acid (AA) is an essential fatty acid that is released by phospholipids in cell membranes and metabolized by cyclooxygenase (COX), cytochrome P450 (CYP) enzymes, and lipid oxygenase (LOX) pathways to regulate complex cardiovascular function under physiological and pathological conditions. Various AA metabolites include prostaglandins, prostacyclin, thromboxanes, hydroxyeicosatetraenoic acids, leukotrienes, lipoxins, and epoxyeicosatrienoic acids. The AA metabolites play important and differential roles in the modulation of vascular tone, and cardiovascular complications including atherosclerosis, hypertension, and myocardial infarction upon actions to different receptors and vascular beds. This article reviews the roles of AA metabolism in cardiovascular health and disease as well as their potential therapeutic implication.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effects of Arachidonic Acid Metabolites on Cardiovascular Health and Disease

Zhou¹,

Khan

Xiao

et al. 2021

IJMS

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“…None of these eight SNPs was associated with key confounders ( Table S5 ). The eight SNPs each had an F-statistic > 10 and collectively explained 5.3% of the variance in AA synthesis, while rs174547 explained 32% of the variance in AA synthesis [ 8 ] ( Table S4 ). Two SNPs (rs259874 and rs472031) were not available for coagulation and had no proxy, while all of the SNPs were available for other outcomes.…”

Section: Resultsmentioning

confidence: 99%

“…In contrast, concern has arisen about the potential harm of arachidonic acid (AA), an important long-chain omega-6 PUFA derived from dietary intake of animal foods (e.g., meat, egg, and liver) [ 6 ], possibly because AA competes with EPA for cyclooxygenase and lipoxygenase to form eicosanoids with potential effects on inflammatory and coagulation pathways [ 7 ]. Recently, Mendelian randomization (MR) studies, using genetic instruments to predict plasma phospholipid AA, have suggested positive effects on ischemic heart disease (IHD) and ischemic stroke [ 8 , 9 , 10 ]. Whether AA affects CVD risk factors, such as lipid profile, blood pressure, adiposity, inflammation and coagulation, and whether any of them mediates the relation of AA with IHD and ischemic stroke is unknown.…”

Section: Introductionmentioning

confidence: 99%

Associations of Arachidonic Acid Synthesis with Cardiovascular Risk Factors and Relation to Ischemic Heart Disease and Stroke: A Univariable and Multivariable Mendelian Randomization Study

2021

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Arachidonic acid (AA), a major long-chain omega-6 polyunsaturated fatty acid, is associated with ischemic heart disease (IHD) and stroke. We assessed bi-directional associations of AA synthesis reflected by plasma phospholipid AA with CVD risk factors, and identified mediators of associations of AA with IHD and stroke using Mendelian randomization (MR). We used two-sample MR to assess bi-directional associations of AA synthesis with lipids, blood pressure, adiposity, and markers of inflammation and coagulation. We used multivariable MR to assess mediators of associations of AA with IHD and stroke. Genetically predicted AA (% of total fatty acids increase) was positively associated with apolipoprotein B (ApoB, 0.022 standard deviations (SD), 95% confidence interval (CI) 0.010, 0.034), high-density (0.030 SD, 95% CI 0.012, 0.049) and low-density lipoprotein cholesterol (LDL-C, 0.016 SD, 95% CI 0.004, 0.027) and lower triglycerides (−0.031 SD, 95% CI −0.049, −0.012) but not with other traits. Genetically predicted these traits gave no association with AA. The association of AA with IHD was attenuated adjusting for ApoB or LDL-C. Genetically predicted AA was associated with lipids but not other traits. Given ApoB is thought to be the key lipid in IHD, the association of AA with IHD is likely mediated by ApoB.

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“…Therefore, an MR study would provide more robust evidence regarding the causal relationship between fatty acids and frailty than observational studies. However, to our knowledge, no MR study has yet investigated the associations between fatty acids and frailty, although there have been several MR studies on the relationship between fatty acids and cardiovascular disease [13][14][15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Fatty Acids and Frailty: A Mendelian Randomization Study

et al. 2021

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Background: Observational studies have suggested that fatty acids such as higher levels of n-3 polyunsaturated fatty acids (PUFAs) may prevent frailty. By using Mendelian randomization analysis, we examined the relationship between fatty acids and frailty. Methods: We used summary statistics data for single-nucleotide polymorphisms associated with plasma levels of saturated fatty acids (palmitic acid, stearic acid), mono-unsaturated fatty acids (MUFAs) (palmitoleic acid, oleic acid), n-6 PUFAs (linoleic acid, arachidonic acid), and n-3 PUFAs (alpha-linolenic acid, eicosapentaenoic acid, docosapentaenoic acid, docosahexaenoic acid), and the corresponding data for frailty index (FI) in 356,432 individuals in the UK Biobank. Results: Although there were no robust associations on the MUFAs or the PUFAs, genetically predicted higher plasma stearic acid level (one of saturated fatty acids) was statistically significantly associated with higher FI (β = 0.178; 95% confidence interval = −0.050 to 0.307; p = 0.007). Such a relationship was also observed in a multivariate MR (β = 0.361; 95% confidence interval = 0.155 to 0.567; p = 0.001). Genetically predicted higher palmitic acid was also significantly associated with higher FI (β = 0.288; 95% confidence interval = 0.128 to 0.447; p < 0.001) in the multivariate MR analysis. Conclusions: The present MR study implies that saturated fatty acids, especially stearic acid, is a risk factor of frailty.

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The associations of plasma phospholipid arachidonic acid with cardiovascular diseases: A Mendelian randomization study

Cited by 32 publications

References 49 publications

Effects of Arachidonic Acid Metabolites on Cardiovascular Health and Disease

Effects of Arachidonic Acid Metabolites on Cardiovascular Health and Disease

Associations of Arachidonic Acid Synthesis with Cardiovascular Risk Factors and Relation to Ischemic Heart Disease and Stroke: A Univariable and Multivariable Mendelian Randomization Study

Fatty Acids and Frailty: A Mendelian Randomization Study

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