Lipoprotein-associated phospholipase A₂ activity is increased in patients with definite familial hypercholesterolemia compared with other forms of hypercholesterolemia

Mattina, Alessandro; Rosenbaum, David; Bittar, Randa; Bonnefont‐Rousselot, Dominique; Noto, Davide; Averna, Maurizio; Bruckert, Éric; Giral, Philippe

doi:10.1016/j.numecd.2018.01.012

Cited by 7 publications

(4 citation statements)

References 48 publications

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“…Plasma Lp-PLA 2 activity is also discovered to be higher in subjects with definite familial hypercholesterolemia (FH) than in nondefinite FH subjects, independently of LDL-C concentrations and statin consumption. This confirms that FH patients present higher arterial inflammation, which may contribute to a higher CVD risk [37].…”

Section: Role Of Phospholipase a 2 In Athero-sclerosissupporting

confidence: 80%

Phospholipase A2 is an Inflammatory Predictor in Cardiovascular Diseases: Is there any Spacious Room to Prove the Causation?

Santoso¹

2020

CCR

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Lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ) is an enzyme family of phospholipase A 2 produced by the inflammatory cell in atherosclerotic plaque. It is transported in the circulation, attached mainly to low-density lipoprotein-cholesterol (LDL-C). It hydrolyzes glycerophospholipids particularly fatty acids at the sn-2 position and produces numerous bioactive lipids; and leads to endothelial dysfunction, atherosclerotic plaque inflammation, and development of the necrotic core in plaques.There are two kinds of phospholipase A 2 , namely: secretory phospholipase A 2 (sPLA 2 ) and Lp-PLA 2 . They are deemed as evolving predictors of cardiovascular disease (CVD) risk in hospitaland population-based studies, including healthy subjects, acute coronary syndromes (ACS) and patients with CVD. Unfortunately, Lp-PLA 2 inhibitor (darapladib) and s-PLA 2 inhibitor (varespladib methyl) failed to prove to lower the risk of composite CVD mortality, myocardial infarction and stroke in those with stable CVD and ACS.Herein, we describe the explanation based on the existing data why there is still a discrepancy among them. So, it highlights the opinion that phospholipase A 2 is merely the inflammatory biomarkers of CVD and playing an important role in atherosclerosis. Further, there is more spacious room to prove the causation.

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Section: Role Of Phospholipase a 2 In Athero-sclerosissupporting

confidence: 80%

Phospholipase A2 is an Inflammatory Predictor in Cardiovascular Diseases: Is there any Spacious Room to Prove the Causation?

Santoso¹

2020

CCR

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“…In addition, lysophosphatidylcholine and oxidized fatty acids may feedback to stimulate macrophages to produce more Lp-PLA2. This cycle accelerates the progression of AS, promotes plaque instability and increases the risk of cardiovascular events (15)(16)(17)(18)(19). In 2012, the American and European guidelines recommended the incorporation of Lp-PLA2 measurements into patient cardiovascular risk assessment protocol (20,21).…”

Section: Discussionmentioning

confidence: 99%

Predictive value of combining the level of lipoprotein-associated phospholipase A2 and antithrombin III for acute coronary syndrome risk

Niu

Zheng

et al. 2018

biom rep

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The aim of the present study was to observe the role of lipoprotein-associated phospholipase A2 (Lp-PLA2) and antithrombin III (AT-III) in patients with acute coronary syndrome (ACS), and the combination of Global Registry of Acute Coronary Events (GRACE) score to determine the value of coronary heart disease risk stratification. A total of 309 patients admitted to the Affiliated Hospital of Xuzhou Medical University were enrolled. The patients were divided into two groups: The ACS (183 cases) and control (126 cases) groups. Blood levels of Lp-PLA2 and AT-III were measured. Based on GRACE score, the patients with ACS were divided into three subgroups: Low risk (GRACE score ≤108), middle risk (GRACE score 109-140) and high risk (GRACE score >140). The levels of Lp-PLA2 and AT-III were compared among different groups, and based on Gensini score, patients with ACS were divided into four groups by quartiles. Lp-PLA2 levels in the ACS group were significantly increased compared with the control group (P<0.05), but the AT-III levels were decreased compared with the control group (P<0.05). In the ACS group, Lp-PLA2 levels increased sequentially from the low risk to high risk subgroups (all P<0.05); compared with the low risk and middle risk subgroups, the AT-III activity levels were decreased in the high risk subgroup, and the Gensini scores were increased (all P<0.05). In the ACS group, with the increase of Gensini scores, the levels of Lp-PLA2 and AT-III exhibited increasing and decreasing trends, respectively (P<0.05). The logistic regression model demonstrated that Lp-PLA2 [odds ratio (OR) =1.077; P<0.001]; and GRACE score (OR=1.026; P=0.028) were risk factors, while AT-III was a protective factor (OR=0.958; P=0.012) for ACS. Correlation analysis indicated a positive association of Lp-PLA2 level with Gensini scores (r= 0.52; P<0.01) and GRACE score (r= 0.48; P<0.01), and a negative association between AT-III level and Gensini scores (r=-0.25; P<0.01) and GRACE scores (r=-0.34; P<0.01). The levels of Lp-PLA2 and AT-III exhibited predictive values in patients with ACS, and are associated with the severity of coronary artery stenosis.

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“…Several studies document implication of proinflammatory LPCs in the pathogenesis of atherosclerosis [78][79][80]. Although underlying mechanisms of LPC increase in hypercholesterolemia remain unknown, plasma Lp-PLA2 activity is elevated in FH [81], potentially accounting for the enrichment in HDL of LPC species. Furthermore, we observed an overall depletion of several PL classes, including PA, PS, PG, PE and PCs, in FH-PCSK9 HDL as compared to both FH-LDLR patients and to normolipidemic controls.…”

Section: Discussionmentioning

confidence: 99%

Integrated omics approach for the identification of HDL structure-function relationships in PCSK9-related familial hypercholesterolemia

Darabi,

Lhomme,

Ponnaiah

et al. 2023

Journal of Clinical Lipidology

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Lipoprotein-associated phospholipase A₂ activity is increased in patients with definite familial hypercholesterolemia compared with other forms of hypercholesterolemia

Cited by 7 publications

References 48 publications

Phospholipase A2 is an Inflammatory Predictor in Cardiovascular Diseases: Is there any Spacious Room to Prove the Causation?

Phospholipase A2 is an Inflammatory Predictor in Cardiovascular Diseases: Is there any Spacious Room to Prove the Causation?

Predictive value of combining the level of lipoprotein-associated phospholipase A2 and antithrombin III for acute coronary syndrome risk

Integrated omics approach for the identification of HDL structure-function relationships in PCSK9-related familial hypercholesterolemia

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