1.Research Advance of Chinese Medicine in Treating Atherosclerosis: Focus on Lipoprotein-Associated Phospholipase A2.
Lu-Ming WANG ; Wen-Lan ZHANG ; Nuan LYU ; Yan-Rong SUO ; Lin YANG ; Bin YU ; Xi-Juan JIANG
Chinese journal of integrative medicine 2024;30(3):277-288
As a serious cardiovascular disease, atherosclerosis (AS) causes chronic inflammation and oxidative stress in the body and poses a threat to human health. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a member of the phospholipase A2 (PLA2) family, and its elevated levels have been shown to contribute to AS. Lp-PLA2 is closely related to a variety of lipoproteins, and its role in promoting inflammatory responses and oxidative stress in AS is mainly achieved by hydrolyzing oxidized phosphatidylcholine (oxPC) to produce lysophosphatidylcholine (lysoPC). Moreover, macrophage apoptosis within plaque is promoted by localized Lp-PLA2 which also promotes plaque instability. This paper reviews those researches of Chinese medicine in treating AS via reducing Lp-PLA2 levels to guide future experimental studies and clinical applications related to AS.
Humans
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1-Alkyl-2-acetylglycerophosphocholine Esterase
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Medicine, Chinese Traditional
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Atherosclerosis/drug therapy*
;
Lipoproteins
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Plaque, Atherosclerotic
;
Biomarkers
2.Effect of Pitavastatin Treatment on ApoB-48 and Lp-PLA2 in Patients with Metabolic Syndrome: Substudy of PROspective Comparative Clinical Study Evaluating the Efficacy and Safety of PITavastatin in Patients with Metabolic Syndrome.
Hyo Sun LEE ; Chang Hee JUNG ; Sung Rae KIM ; Hak Chul JANG ; Cheol Young PARK
Endocrinology and Metabolism 2016;31(1):120-126
BACKGROUND: Apolipoprotein (Apo) B-48 is an intestinally derived lipoprotein that is expected to be a marker for cardiovascular disease (CVD). Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a vascular-specific inflammatory marker and important risk predictor of CVD. The aim of this study was to explore the effect of pitavastatin treatment and life style modification (LSM) on ApoB-48 and Lp-PLA2 levels in metabolic syndrome (MS) patients at relatively low risk for CVD, as a sub-analysis of a previous multi-center prospective study. METHODS: We enrolled 75 patients with MS from the PROPIT study and randomized them into two treatment groups: 2 mg pitavastatin daily+intensive LSM or intensive LSM only. We measured the change of lipid profiles, ApoB-48 and Lp-PLA2 for 48 weeks. RESULTS: Total cholesterol, low density lipoprotein cholesterol, non-high density lipoprotein cholesterol, and ApoB-100/A1 ratio were significantly improved in the pitavastatin+LSM group compared to the LSM only group (P≤0.001). Pitavastatin+LSM did not change the level of ApoB-48 in subjects overall, but the level of ApoB-48 was significantly lower in the higher mean baseline value group of ApoB-48. The change in Lp-PLA2 was not significant after intervention in either group after treatment with pitavastatin for 1 year. CONCLUSION: Pitavastatin treatment and LSM significantly improved lipid profiles, ApoB-100/A1 ratio, and reduced ApoB-48 levels in the higher mean baseline value group of ApoB-48, but did not significantly alter the Lp-PLA2 levels.
1-Alkyl-2-acetylglycerophosphocholine Esterase*
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Apolipoprotein B-48*
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Apolipoproteins
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Cardiovascular Diseases
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Cholesterol
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Cholesterol, LDL
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Humans
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Life Style
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Lipoproteins
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Prospective Studies*
3.Elevated plasma lipoprotein-associated phospholipase A₂ activity is associated with plaque rupture in patients with coronary artery disease.
Chuan-Fen LIU ; Li QIN ; Jing-Yi REN ; Hong CHEN ; Wei-Min WANG ; Jian LIU ; Jun-Xian SONG ; Li-Jun LI
Chinese Medical Journal 2011;124(16):2469-2473
BACKGROUNDLipoprotein-associated phospholipase A(2) (Lp-PLA(2)) has recently been shown to be positively related to coronary events in patients with coronary artery disease (CAD). However, direct evidence about the relationship between circulation Lp-PLA(2) activity and vulnerable plaque in patients with CAD remains lacking.
METHODSPlasma Lp-PLA(2) activity was determined in 146 consecutive patients with CAD who underwent clinically-indicated coronary angiography and preinterventional intravascular ultrasound (IVUS).
RESULTSEighty-three patients were included in the final analysis after the initial screening. Sixty (72.3%) were acute coronary syndrome (ACS) patients and 23 (27.7%) were stable angina pectoris (SAP) patients. Plaque rupture occurred in 39 (47.0%) patients, and 34 (87.2%) were from ACS patients and 5 (12.8%) from SAP patients. There were no significant differences in clinical and angiographic characteristics between patients with plaque rupture and those without plaque rupture, except for smoking, high-sensitive C-reactive protein (hs-CRP) level and Lp-PLA(2) activity (all P < 0.05). IVUS measurement uncovered that patients with plaque rupture had more frequent positive remodeling (74.4% vs. 43.2%, P = 0.004), soft plaques (64.1% vs. 36.4%, P = 0.012) and higher remodeling index (1.13 ± 0.16 vs. 0.99 ± 0.11, P = 0.041) as compared with those without plaque rupture. Multivariate Logistic regression analysis showed that plasma Lp-PLA(2) activity was independently associated with plaque rupture after adjusting for smoking, positive remodeling and soft plaque (Model 1: odds ratio (OR) 1.13, 95% confidence interval (CI): 1.06 - 1.20) or adjusting for smoking, hs-CRP level, positive remodeling and soft plaque (Model 2: OR 1.11, 95%CI: 1.04 - 1.19).
CONCLUSIONSPlasma Lp-PLA(2) activity is associated with plaque rupture in patients with CAD, independently of traditional CAD risk factors, hs-CRP level and IVUS parameters. Lp-PLA(2) may be a risk marker for vulnerable plaques.
1-Alkyl-2-acetylglycerophosphocholine Esterase ; blood ; Aged ; Coronary Artery Disease ; blood ; diagnostic imaging ; pathology ; Female ; Humans ; Male ; Middle Aged ; Radiography
4.Association between platelet-activating factor acetylhydrolase gene polymorphism and intracranial hemorrhage in preterm infants.
Qian ZHANG ; Xin-Ru CHENG ; Shu-Ling XU ; Zan-Yang SHI ; Guang-Yao SHENG
Chinese Journal of Contemporary Pediatrics 2012;14(8):612-615
OBJECTIVETo explore whether Val279Phe single nucleotide polymorphisms (SNPs) in the 9th exon of platelet-activating factor acetylhydrolase (PAF-AH) are associated with intracranial hemorrhage in preterm infants.
METHODSA case-control study was performed. Polymerase chain reaction (PCR) was used to test genotype and allele frequencies of the 9th exon Val279Phe SNPs of PAF-AH in 58 preterm infants with intracranial hemorrhage (hemorrhage group) and 65 preterm infants without intracranial hemorrhage (control group).
RESULTSThere were significant differences in genotype frequency of Val279Phe SNPs in the 9th exon of PAF-AH between the hemorrhage and control groups (P<0.05). Frequency of normal genotype in the hemorrhage group (63.8%) was significantly lower than in the control group (81.5%). In contrast, frequency of heterozygous genotype (34.5%) in the hemorrhage group was significantly higher than in control group (16.9%). There were also significant differences in allele frequency of Val279Phe SNPs in the 9th exon of PAF-AH between the two groups (P<0.05). T allele frequency in the hemorrhage group (19.0%) was significantly higher than in the control group (10.0%).
CONCLUSIONSVal279Phe SNPs in the 9th exon of PAF-AH may be associated with intracranial hemorrhage in preterm infants.
1-Alkyl-2-acetylglycerophosphocholine Esterase ; genetics ; Female ; Humans ; Infant, Newborn ; Infant, Premature ; Intracranial Hemorrhages ; etiology ; genetics ; Male ; Polymorphism, Single Nucleotide
5.Red blood cell distribution width combined with lipoprotein-associated phospholipase A2 detection for improving diagnostic accuracy of coronary artery stenosis in patients with coronary artery disease.
Ji-Chen LIU ; Kai GUO ; Hao LU ; Meng-Hao LI ; Wen-Yan LAI ; Zhi-Gang GUO
Journal of Southern Medical University 2016;36(6):875-879
OBJECTIVETo study the association of red blood cell distribution width (RDW) and lipoprotein-associated phospholipase A2 (LP-PLA2) with the degree of coronary artery stenosis in patients with coronary artery disease (CAD) and the value of RDW combined with LP-PLA2 detection in accurate evaluation of coronary artery stenosis.
METHODSA total of 224 patients including 119 non-CAD cases and 105 CAD cases admitted in our hospital between June, 2013 and June, 2014 were enrolled in this study. The patients' baseline clinical data were collected and venous blood samples were obtained for detecting WBC, RDW-CV and LP-PLA2. The Gensini score of the CAD patients was calculated based on coronary angiographic findings.
RESULTSCompared with the non-CAD patients, CAD patients had significantly higher RDW-CV (P=0.009) and LP-PLA2 (P=0.004) levels. The CAD patients with high Gensini scores had also significantly higher RDW-CV (P=0.001) and LP-PLA2 (P<0.001) levels than those with low scores; RDW-CV and LP-PLA2 were significantly correlated with the Gensini score, and the area under curve of their combined detection was 0.931.
CONCLUSIONCombination of RDW and LP-PLA2 can improve the diagnostic accuracy of the degree of coronary artery stenosis in patients with CAD.
1-Alkyl-2-acetylglycerophosphocholine Esterase ; blood ; Coronary Angiography ; Coronary Artery Disease ; diagnosis ; Coronary Stenosis ; diagnosis ; Erythrocyte Count ; Erythrocytes ; cytology ; Humans
6.Development and application of monoclonal antibodies anti-human lipoprotein-associated phospholipase A2.
Wen XU ; Zhaoxin LU ; Lin CAO
Chinese Journal of Biotechnology 2019;35(3):482-491
The aim of this study is to prepare monoclonal anti-human Lp-PLA2 antibodies, and establish a rapid and accurate immunochromatographic Lp-PLA2 assay used in community medical institution. The gene sequence of human Lp-PLA2 was obtained from NCBI to construct the expression plasmid. Lp-PLA2 protein expressed in CHO-K1 cells was used to immune BALB/c mice. The monoclonal antibodies were produced in mouse ascites after hybridoma cells screening. Antibodies were evaluated by SDS-PAGE, ELISA and other methods. The Lp-PLA2 test strip was prepared based on sandwich method and evaluated with the portable detection instrument. The affinity of the paired antibodies, PLA1 and PLA5, both reached 1×10⁻⁸. The antibody subclass was IgG1. Both antibodies recognized the Lp-PLA2 protein in the blood specifically. The Lp-PLA2 test strip was prepared based on sandwich method, with linear range of 20-2000 ng/mL. The Lp-PLA2 test strip correlated well with the diaDexus ELISA test kit. In conclusion, the paired antibodies were successfully prepared with high affinity and specificity. The immunochromatographic test of Lp-PLA2 provided a fast and accurate method to detect the concentration of Lp-PLA2 in blood sample for clinical use in the community medical institution and could contribute to the management of cardiovascular diseases.
1-Alkyl-2-acetylglycerophosphocholine Esterase
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metabolism
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Animals
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Antibodies, Monoclonal
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Enzyme-Linked Immunosorbent Assay
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Humans
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Mice
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Mice, Inbred BALB C
7.Correlation between smoking and serum lipoprotein-associated phospholipase A2 level in overweight and obese men.
Journal of Central South University(Medical Sciences) 2023;48(2):191-197
OBJECTIVES:
Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a vaso-specific inflammatory marker that exacerbates atherosclerotic through inflammatory responses. It can be used to predict the occurrence of adverse cardiovascular events and to assess the residual risk of cardiovascular diseases. This study aims to investigate the correlation between smoking and serum Lp-PLA2 levels in overweight and obese men, and to provide evidence for preventing the cardiovascular diseases.
METHODS:
Male subjects, who participated in health examination at the Health Management Center, Third Xiangya Hospital, Central South University from May 1, 2020 to April 30, 2021, were selected. The smoking status and other information were collected by the Self-test Scale of Physical Examination. According to the smoking status, they were divided into a never-smoking group, a current smoking group, a quit smoking group and a passive smoking group. According to the daily smoking amount, the current smoking subjects were divided into a <10 cigarettes group, a 10 to 20 cigarettes group, a 21 to 30 cigarettes group, and a >30 cigarettes group. According to the smoking years, the current smoking subjects were divided into a <5 years group, a 5 to 10 years group, a 11 to 20 years group, and a >20 years group.Serum Lp-PLA2 levels and other clinical indexes in different smoking groups were measured and compared, the correlation between smoking and serum Lp-PLA2 levels in overweight and obese men was analyzed by logistic regression analysis.
RESULTS:
Serum Lp-PLA2 levels were significantly different between the never-smoking group and the current smoking group (P<0.05). Logistic regression analysis showed that, before adjusting other influencing factors and in terms of smoking status, the current smoking group (OR=1.81, 95% CI 1.27 to 2.58, P<0.01) and the quit smoking group (OR=2.09, 95% CI 1.12 to 3.90, P<0.05) were positively correlated with serum Lp-PLA2 levels compared with the never-smoking group, while the passive smoking group had no correlation with serum Lp-PLA2 levels (OR=1.27, 95% CI 0.59 to 2.73, P>0.05). In terms of daily smoking amount, the 10 to 20 cigarettes group (OR=2.09, 95% CI 1.40 to 3.12, P<0.001) and the 21 to 30 cigarettes group (OR=1.98, 95% CI 1.22 to 3.20, P<0.01) were positively correlated with serum Lp-PLA2 levels compared with the never-smoking group, while the <10 cigarettes group (OR=1.45, 95% CI 0.81 to 2.60, P>0.05) and the >30 cigarettes group (OR=1.17, 95% CI 0.60 to 2.28, P>0.05) had no correlation with serum Lp-PLA2 levels. In terms of smoking years, the 5 to 10 years group (OR=1.94, 95% CI 1.07 to 3.53, P<0.05), the 11 to 20 years group (OR=2.06, 95% CI 1.33 to 3.18, P<0.01), and the >20 years group (OR=1.66, 95% CI 1.11 to 2.47, P<0.05) were positively correlated with serum Lp-PLA2 levels compared with the never-smoking group, while the <5 years group had no correlation with serum Lp-PLA2 levels (OR=1.12, 95% CI 0.38 to 3.33, P>0.05). After adjusting for age and other indicators, the correlation between smoking years and serum Lp-PLA2 levels was the same as before adjustment among the above smoking groups, except that the correlation between the smoking 5 to 10 years group and serum Lp-PLA2 levels was not significant (OR=1.77, 95% CI 0.95 to 3.29, P>0.05).
CONCLUSIONS
Smoking is correlated with serum Lp-PLA2 levels in overweight and obese men.
Humans
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Male
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1-Alkyl-2-acetylglycerophosphocholine Esterase
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Overweight
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Cardiovascular Diseases
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Tobacco Smoke Pollution
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Biomarkers
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Obesity
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Smoking
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Risk Factors
8.Correlation between blood-stasis tongue figure and platelet activating factor (PAF) and acetyl hydrolase of PAF (PAF-AH) in patients with primary dysmenorrhea.
Chinese Journal of Integrated Traditional and Western Medicine 2011;31(3):331-333
OBJECTIVETo explore the pathologic mechanism of blood-stasis tongue figure (BSTF) formation in patients with primary dysmenorrhea.
METHODSBlood levels of platelet activating factor (PAF) and acetyl hydrolase of PAF (PAF-AH) in 41 patients with primary dysmenorrhea and 20 healthy subjects were detected by enzyme linked immunosorbent assay (ELISA).
RESULTSThe level of PAF in the 22 patients with BSTF was 252. 214 +/- 37. 568 ng/L, which was higher than that in patients without BSTF (19 patients, 212.348 +/- 22.794 ng/L) and healthy subjects (182.126 +/- 18.306 ng/L) respectively, while level of PAF-AH showed an opposite sequence in them, i.e., 3.090 +/- 1.483, 5.382 +/- 1.873, and 5.607 +/- 2.073 ng/L, respectively (P < 0.05). Patients without BSTF showed only a higher level of PAF when compared with that in healthy subjects (P < 0.05). No significant difference in PAF or PAF-AH levels was shown among patients with BDTF of different Chinese medical syndrome types (P > 0.05).
CONCLUSIONPAF level obviously increased and PAF-AH level obviously decreased in primary dysmenorrhea patients of BSTF, suggesting that the imbalance of PAF and PAF-AH was correlated with the pathologic mechanism of the BSTF formation in primary dysmenorrhea patients.
1-Alkyl-2-acetylglycerophosphocholine Esterase ; blood ; Adolescent ; Case-Control Studies ; Dysmenorrhea ; blood ; diagnosis ; pathology ; Female ; Humans ; Medicine, Chinese Traditional ; Platelet Activating Factor ; metabolism ; Tongue ; Young Adult
10.Correlation between PAFAH1B3 Expression Level and Risk of Disease Progression After Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma Patients.
Zhe-Yun GU ; Jian TAO ; Yi-Feng CAI ; Ling WANG
Journal of Experimental Hematology 2023;31(2):448-454
OBJECTIVE:
To investigate the association between the expression level of platelet-activating factor acetylhydrolase 1B3 (PAFAH1B3 ) gene in bone marrow CD138+ cells of patients with multiple myeloma (MM) treated with autologous hematopoietic stem cell transplantation (AHSCT) and the prognosis within 2 years.
METHODS:
147 MM patients treated with AHSCT in The First and The Second Affiliated Hospital of Nantong University from May 2014 to May 2019 were included in the study. Expression level of PAFAH1B3 mRNA in bone marrow CD138+ cells of the patients was detected. Patients with disease progression or death during 2 years of follow-up were included in progression group, and the rest were included in good prognosis group. After comparing the clinical data and PAFAH1B3 mRNA expression levels of the two groups, the patients were divided into high PAFAH1B3 expression group and low PAFAH1B3 expression group based on the median PAFAH1B3 mRNA expression level of the enrolled patients. Progression-free survival rate (PFSR) between the two groups was compared by the Kaplan-Meier method. The related factors of prognosis within 2 years were analyzed by univariate analysis and multivariate COX regression analysis.
RESULTS:
At the end of follow-up, there were 13 patients lost to follow-up. Finally, 44 patients were included in the progression group and 90 patients were included in the good prognosis group. Age in the progression group was higher than that in the good prognosis group, the proportion of patients with CR+VGPR after transplantation in the progression group was lower than that in the good prognosis group, and there was a statistical difference between two groups in the cases distribution of ISS stage (all P<0.05). PAFAH1B3 mRNA expression level and the proportion of patients with LDH>250U/L in the progression group were higher than those in the good prognosis group, and platelet count in the progression group was lower than that in the good prognosis group (all P<0.05). Compared with the low PAFAH1B3 expression group, the 2-year PFSR of the high PAFAH1B3 expression group was significantly lower (log-rank χ2=8.167, P=0.004). LDH>250U/L (HR=3.389, P=0.010), PAFAH1B3 mRNA expression (HR=50.561, P=0.001) and ISS stage Ⅲ(HR=1.000, P=0.003) were independent risk factors for prognosis in MM patients, and ISS stage Ⅰ (HR=0.133, P=0.001) was independent protective factor.
CONCLUSION
The expression level of PAFAH1B3 mRNA in bone marrow CD138+ cells is related to the prognosis of MM patients treated with AHSCT, and detecting PAFAH1B3 mRNA expression can bring some information for predicting PFSR and prognostic stratification of patients.
Humans
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Disease Progression
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Hematopoietic Stem Cell Transplantation
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Multiple Myeloma/drug therapy*
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Prognosis
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Retrospective Studies
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Transplantation, Autologous
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1-Alkyl-2-acetylglycerophosphocholine Esterase/genetics*