Regulation of lipoprotein-associated phospholipase A2 silencing on myocardial fibrosis in mice with coronary atherosclerosis

Pan, Guozhong; Kou, Lanjun; Wu, Yang Chang; Hu, Yuanji; Lin, Xiaoshuo; Guo, Jinrui; Ren, Xiaoxia; Yan, Zhang

doi:10.1016/j.bbrc.2019.04.129

Cited by 6 publications

(4 citation statements)

References 21 publications

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“…18 Lp-PLA 2 silencing effectively decreased LDL-C levels in ApoE-deficient atherosclerotic mice. 50 Our study determined that Lp-PLA 2 deficiency causally reduces LDL-C levels in rabbits, indicating the potential of Lp-PLA 2 as a target for CVD prevention. Mechanistically, Lp-PLA 2 deficiency did not affect LDLR-mediated cholesterol uptake from the blood.…”

Section: Discussionmentioning

confidence: 64%

Lp-PLA ₂ (Lipoprotein-Associated Phospholipase A ₂ ) Deficiency Lowers Cholesterol Levels and Protects Against Atherosclerosis in Rabbits

Chen

Zhang

et al. 2023

ATVB

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Background: Elevated plasma Lp-PLA 2 (lipoprotein-associated phospholipase A 2 ) activity is closely associated with an increased risk of cardiovascular events. However, whether and how Lp-PLA 2 is directly involved in the pathogenesis of atherosclerosis is still unclear. To examine the hypothesis that Lp-PLA 2 could be a potential preventative target of atherosclerosis, we generated Lp-PLA 2 knockout rabbits and investigated the pathophysiological functions of Lp-PLA 2 . Methods: Lp-PLA 2 KO rabbits were generated using CRISPR/Cas9 system to assess the role of Lp-PLA 2 in plasma lipids regulation and identify its underlying molecular mechanisms. Homozygous knockout rabbits along with wild-type rabbits were fed a cholesterol-rich diet for up to 14 weeks and their atherosclerotic lesions were compared. Moreover, the effects of Lp-PLA 2 deficiency on the key cellular behaviors in atherosclerosis were assessed in vitro. Results: When rabbits were fed a standard diet, Lp-PLA 2 deficiency led to a significant reduction in plasma lipids. The decreased protein levels of SREBP2 (sterol regulatory element-binding protein 2) and HMGCR (3-hydroxy-3-methylglutaryl coenzyme A reductase) in livers of homozygous knockout rabbits indicated that the cholesterol biosynthetic pathway was impaired with Lp-PLA 2 deficiency. In vitro experiments further demonstrated that intracellular Lp-PLA 2 efficiently enhanced SREBP2-related cholesterol biosynthesis signaling independently of insulin-induced genes ( INSIG s). When fed a cholesterol-rich diet, homozygous knockout rabbits exhibited consistently lower level of hypercholesterolemia, and their aortic atherosclerosis lesions were significantly reduced by 60.2% compared with those of wild-type rabbits. The lesions of homozygous knockout rabbits were characterized by reduced macrophages and the expression of inflammatory cytokines. Macrophages of homozygous knockout rabbits were insensitive to M1 polarization and showed reduced DiI-labeled lipoprotein uptake capacity compared with wild-type macrophages. Lp-PLA 2 deficiency also inhibited the adhesion between monocytes and endothelial cells. Conclusions: These results demonstrate that Lp-PLA 2 plays a causal role in regulating blood lipid homeostasis and Lp-PLA 2 deficiency protects against dietary cholesterol-induced atherosclerosis in rabbits. Lp-PLA 2 could be a potential target for the prevention of atherosclerosis.

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Section: Discussionmentioning

confidence: 64%

Lp-PLA ₂ (Lipoprotein-Associated Phospholipase A ₂ ) Deficiency Lowers Cholesterol Levels and Protects Against Atherosclerosis in Rabbits

Chen

Zhang

et al. 2023

ATVB

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“…Therefore, IMA can be used as a serum marker for monitoring the severity of LEASOD. Lipoprotein phospholipase A2 (LP-PLA2) is a new vascular-specific inflammatory marker, also known as plasma platelet activator acetylhydrolase, which is mainly secreted by macrophages and lymphocytes in atherosclerotic plaques and regulated by inflammatory mediators (31,32). The LP-PLA2 in plasma mainly existed in the form of lipoprotein particle binding, of which about 70-80% is bound to a low-density lipoprotein cholesterol to promote the occurrence of inflammatory reaction, while the remaining 20-30% of LP-PLA2 is bound to a highdensity lipoprotein cholesterol or a very low-density lipoprotein cholesterol to play an important role in the anti-oxidation and anti-atherosclerosis effects (33,34).…”

Section: Discussionmentioning

confidence: 99%

Correlation of Serum CysC, IMA, and LP-PLA2 Levels With Type 2 Diabetes Mellitus Patients With Lower Extremity Atherosclerotic Occlusive Disease

et al. 2022

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ObjectiveTo investigate the serum level of cystatin C (CysC), ischemia-modified albumin (IMA), and lipoprotein-associated phospholipase A2 (LP-PLA2) in patients with type 2 diabetes mellitus (T2DM) and with lower extremity atherosclerotic occlusive disease (LEASOD) and their correlation.MethodsFrom March 2017 to December 2019, 110 patients with T2DM with LEASOD, who were treated in our hospital, were selected as the observation group. One hundred ten healthy persons who received medical examination in our hospital during the same period were selected as the control group. Serum CysC, IMA, LP-PLA2, and ankle-brachial index (ABI) were detected in each group. According to the ABI index, the observation group was divided into three subgroups, namely, the mild group (n = 45), the moderate group (n = 42), and the severe group (n = 23). Pearson correlation analysis was used to analyze the relationship between serum CysC, IMA, and LP-PLA2 levels in patients with T2DM with LEASOD and their condition. The receiver operator characteristic (ROC) curve was used to analyze the diagnostic value of serum CysC, IMA, and LP-PLA2 levels in patients with T2DM with LEASOD.ResultsThe serum levels of CysC, IMA, and LP-PLA2 in the observation group were higher than those in the control group (p < 0.05). The serum levels of CysC, IMA, and LP-PLA2 in the severe and the moderate group were higher than those in the mild group, and the serum levels of CysC, IMA, and LP-PLA2 in the severe group were higher than those in the moderate group (p < 0.05). Pearson correlation analysis showed that CysC, IMA, and LP-PLA2 levels were all negatively correlated with ABI (r = −0.802, r = −0.757, r = −0.764, p < 0.001). The ROC curve results showed that the area under the curve (AUC) of serum CysC in the diagnosis of T2DM with LEASOD was 0.806, and the best cut-off value was 1.74 mg/L. The AUC of serum IMA for diagnosis of T2DM with LEASOD was 0.772, and the best cut-off value was 92.58 g/L. The AUC of serum LP-PLA2 in the diagnosis of T2DM with LEASOD was 0.781, and the best cut-off value was 544.86 ng/L. The AUC of the three combined diagnoses of T2DM with LEASOD was 0.863.ConclusionSerum levels of CysC, IMA, and LP-PLA2 were increased in patients with T2DM with LEASOD. Serum CysC, IMA, and LP-PLA2 are closely related to the severity of the disease. The higher the serum levels of CysC, IMA, and LP-PLA2, the more serious the degree of lower extremity arteriosclerosis occlusion, which can be used as an important serum marker to monitor the severity of T2DM with LEASOD. The combined detection of serum CysC, IMA, and LP-PLA2 has good diagnostic value for patients with T2DM with LEASOD.

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“…We further screened 12 candidate genes, all of which have been shown to be involved in regulating fat deposition. PLA2G6 and PLA2G7 catalyze the hydrolysis of phospholipids (PLs) to generate fatty acids, and their abnormal expression can cause dysregulated lipid metabolism .…”

Section: Discussionmentioning

confidence: 99%

Using Machine Learning to Identify Biomarkers Affecting Fat Deposition in Pigs by Integrating Multisource Transcriptome Information

Liu

Xing

Jiang

et al. 2022

J. Agric. Food Chem.

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Fat deposition in pigs is not only closely related to pig production efficiency and pork quality but also an ideal model for human obesity. Transcriptome sequencing is widely used to study fat deposition. However, due to small sample sizes, high false positive rates, and poor consistency of results from different studies, new strategies are urgently needed. Machine learning, a new analysis method, can effectively fit complex data and accurately identify samples and genes. In this study, 36 samples of adipose tissue, muscle tissue, and liver tissue were collected from Songliao black pigs and Landrace pigs, and the mRNA of all the samples was sequenced. In addition, we collected transcriptome data for 64 samples in the GEO database from four different sources. After standardization and imputation of missing values in the data set comprising 100 samples, traditional differential expression analysis was carried out, and different numbers of expressed genes were selected as features for the training model of eight machine learning methods. In the 1000 replications of fourfold cross validation with 100 samples, AdaBoost performed best, with an average prediction accuracy greater than 93% and the highest mean area under the curve in predicting the high- and low-fat content groups among the eight ML methods. According to their performance-based ranks inferred by AdaBoost, 12 genes related to fat deposition were identified; among them, FASN and APOD were specifically expressed in adipose tissue, and APOA1 was specifically expressed in the liver, which could be important candidate biomarkers affecting fat deposition.

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Regulation of lipoprotein-associated phospholipase A2 silencing on myocardial fibrosis in mice with coronary atherosclerosis

Cited by 6 publications

References 21 publications

Lp-PLA ₂ (Lipoprotein-Associated Phospholipase A ₂ ) Deficiency Lowers Cholesterol Levels and Protects Against Atherosclerosis in Rabbits

Lp-PLA ₂ (Lipoprotein-Associated Phospholipase A ₂ ) Deficiency Lowers Cholesterol Levels and Protects Against Atherosclerosis in Rabbits

Correlation of Serum CysC, IMA, and LP-PLA2 Levels With Type 2 Diabetes Mellitus Patients With Lower Extremity Atherosclerotic Occlusive Disease

Using Machine Learning to Identify Biomarkers Affecting Fat Deposition in Pigs by Integrating Multisource Transcriptome Information

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Regulation of lipoprotein-associated phospholipase A2 silencing on myocardial fibrosis in mice with coronary atherosclerosis

Cited by 6 publications

References 21 publications

Lp-PLA 2 (Lipoprotein-Associated Phospholipase A 2 ) Deficiency Lowers Cholesterol Levels and Protects Against Atherosclerosis in Rabbits

Lp-PLA 2 (Lipoprotein-Associated Phospholipase A 2 ) Deficiency Lowers Cholesterol Levels and Protects Against Atherosclerosis in Rabbits

Correlation of Serum CysC, IMA, and LP-PLA2 Levels With Type 2 Diabetes Mellitus Patients With Lower Extremity Atherosclerotic Occlusive Disease

Using Machine Learning to Identify Biomarkers Affecting Fat Deposition in Pigs by Integrating Multisource Transcriptome Information

Contact Info

Product

Resources

About

Lp-PLA ₂ (Lipoprotein-Associated Phospholipase A ₂ ) Deficiency Lowers Cholesterol Levels and Protects Against Atherosclerosis in Rabbits

Lp-PLA ₂ (Lipoprotein-Associated Phospholipase A ₂ ) Deficiency Lowers Cholesterol Levels and Protects Against Atherosclerosis in Rabbits