Intracranial Aneurysms and Lipid Metabolism Disorders: From Molecular Mechanisms to Clinical Implications

Pan, Tonglin; Shi, Yuan; Yu, Guo; Mamtimin, Abdureshid; Zhu, Wei

doi:10.3390/biom13111652

Cited by 3 publications

(2 citation statements)

References 111 publications

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“…However, no descriptive study has been published on the link between LPE and IAs. Existing studies tend to suggest that physical stimulation of cerebral haemodynamics and the stress response of vascular endothelial cells induced chronic in ammation in the aneurysm wall [10] . While our MR analyses suggested a potential risk association between LPE (18:2) and IAs rupture, the exact mechanisms underlying the role of LPE (18:2) in the development of IAs remain inconclusive.…”

Section: Discussionmentioning

confidence: 99%

“…[9] . While modern lipidomics detection technologies have expanded our comprehension of the diversity and abundance of circulating lipids, the presence of numerous isomeric/isobaric lipid species in cellular lipidomes continues to pose signi cant challenges in regulating the expression and activity of various genes, proteins, and associated signaling pathways [10,11] . Previous studies have primarily focused on the correlation between certain lipoproteins and aneurysms.…”

Section: Introductionmentioning

confidence: 99%

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179 Plasma lipids and risk of intracranial aneurysms: A genetic study of association and causality

Chen,

Mei,

Zhou

et al. 2024

Preprint

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Background Current evidence suggests that genetic factors, hemodynamic abnormalities, and chronic inflammation of the vascular wall contribute to the onset of intracranial aneurysms (IAs). The deposition of lipid plaques is frequently observed in the walls of IAs. Therefore, the objective of this research was to determine the causal link between plasma lipids and IAs. Methods Genetic instrumental variables for 179 plasma lipids were acquired from a genome-wide association study (GWAS) of 7174 unrelated Finnish individuals. Outcome data for individuals with IAs were retrieved from a GWAS involving 23 cohorts, comprising 79,429 individuals of European ancestry. This dataset included 7,495 cases and 71,934 controls. Three databases were utilized for the implementation of Mendelian Randomization (MR) analysis. This included an aSAH group with 5,140 aSAH cases and 71,952 controls, a uIA group with 2,070 uIA cases and 71,952 controls, and an IAs group with 7,495 IAs cases and 71,934 controls. An inverse-variance weighted (IVW) method was employed as the key analysis method. To ensure the reliability of the findings, MR-Egger regression, weighted-median, and weighted-mode methods were employed. Sensitivity analyses included Cochran’s Q test, MR-Pleiotropy RESidual Sum and Outlier (MR-PRESSO), Radial MR test, MR-Egger intercept test, and Leave-one-out (LOO) analysis. The MR-Steiger test was conducted to avoid reverse causality. Results Following rigorous screening, MR tests, and Bonferroni correction, the genetically predicted level of Phosphatidylethanolamine(18:2_0:0)(LPE(18:2))(OR:1.28,95CI:1.13-1.46, P=1.42×10−4) ,Phosphatidylcholine (PC) (16:0_20:4)(OR:0.86,95CI:0.86-0.93, P=1.38×10−4),Phosphatidylcholine (PC) (18:0_20:3)(OR:1.29,95CI:1.12-1.47, P=2.33×10−4)and Phosphatidylcholine (PC) (O-16:0_20:4)(OR:0.83,95CI:0.75-0.91, P=2.22×10−4) showed significant causal relationships with aSAH. Two plasma lipids, LPE (18:2)(OR:1.22,95CI:1.11-1.34, P=3.14×10−5) and PC (16:1_18:2)(OR:1.19,95CI:1.09-1.31, P=1.53×10−4) exhibited a positive correlation with the risk of IAs. No significant causal link was found between uIA and 179 plasma lipids. Conclusion Genetically determined LPE (18:2) ,PC(18:0_20:3) and PC (16:1_18:2) can increase the risk of IAs rupture;while PC(16:0_20:4) and PC (O-16:0_20:4) can reduce the risk of IAs rupture.PCs with arachidonic acid (AA) chains and the metabolism of AA may be crucially involved in the occurrence and development of IAs.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

179 Plasma lipids and risk of intracranial aneurysms: A genetic study of association and causality

Chen,

Mei,

Zhou

et al. 2024

Preprint

View full text Add to dashboard Cite

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Moutan cortex radicis extract alleviates lipid accumulation by modulating endoplasmic reticulum stress in high-fat diet-fed mice

Bai,

Liu,

Peng

et al. 2024

Journal of Functional Foods

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Association of serum lipidomic profiles with risk of intracranial aneurysm: A Mendelian randomization study

Zhang,

Yang,

Wang

et al. 2024

Journal of Neurochemistry

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A two‐sample Mendelian randomization (MR) analysis was utilized to assess the causal relationship between lipidomic profiles and the risk of intracranial aneurysms (IAs). Genetic variants related to lipidomic profiles (227 components) and IA [IA, aneurysmal subarachnoid hemorrhage (aSAH) only, unruptured IA (uIA) only] were obtained from published genome‐wide association studies (GWASs) or the IEU Open GWAS project and used as instrumental variables for MR analysis. The inverse‐variance weighted method was used in the primary analyses to derive causality estimates and was expressed as odds ratio (OR) with 95% confidence interval (CI). Of these 227 lipidomic profiles, only genetically predicted high levels of cholesterol to total lipids ratio in very small very‐low‐density lipoproteins (VLDL) [OR = 0.629 (95% CI, 0.504–0.786)], cholesteryl esters to total lipids ratio in very small VLDL [OR = 0.637 (95% CI, 0.509–0.797)], ratio of docosahexaenoic acid to total fatty acids [OR = 0.691 (95% CI, 0.582–0.820)], and ratio of polyunsaturated fatty acids to monounsaturated fatty acids [OR = 0.630 (95% CI, 0.522–0.760)] reduced the risk of aSAH, whereas genetically predicted high ratio of monounsaturated fatty acids to total fatty acids [OR = 1.471 (95% CI, 1.215–1.781)] increased the risk of aSAH. Moreover, genetically predicted high levels of cholesterol to total lipids ratio in very small VLDL [OR = 0.657 (95% CI, 0.542–0.798)], cholesteryl esters to total lipids ratio in very small VLDL [OR = 0.663 (95% CI, 0.548–0.803)], free cholesterol to total lipids ratio in small VLDL [OR = 0.682 (95% CI, 0.560–0.832)], phospholipids to total lipids ratio in small VLDL [OR = 0.674 (95% CI, 0.548–0.830)], and ratio of polyunsaturated fatty acids to monounsaturated fatty acids [OR = 0.678 (95% CI, 0.569–0.808)] reduced the risk of IA. The results of multivariable MR demonstrated that these causal associations persisted after adjusting for systolic blood pressure and cigarettes smoked per day. The effect of serum lipids on IA and aSAH may be mainly caused by subclasses of lipids such as VLDL.image

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Intracranial Aneurysms and Lipid Metabolism Disorders: From Molecular Mechanisms to Clinical Implications

Cited by 3 publications

References 111 publications

179 Plasma lipids and risk of intracranial aneurysms: A genetic study of association and causality

179 Plasma lipids and risk of intracranial aneurysms: A genetic study of association and causality

Moutan cortex radicis extract alleviates lipid accumulation by modulating endoplasmic reticulum stress in high-fat diet-fed mice

Association of serum lipidomic profiles with risk of intracranial aneurysm: A Mendelian randomization study

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