Lipoprotein-associated Phospholipase A2 Research Articles

Joint association of remnant cholesterol and lipoprotein-associated phospholipase A2 with composite adverse events: A 12-year follow-up study from Asymptomatic Polyvascular Abnormalities Community study.

To explore the association of remnant cholesterol (RC) and lipoprotein-associated phospholipase A2 (Lp-PLA2) with composite adverse events in a large-scale prospective study. All data were collected from the Asymptomatic Polyvascular Abnormalities Community study between 2010 and 2022. Serum cholesterol levels and Lp-PLA2 were determined by enzyme-linked immunosorbent assay. The participants were categorized into four groups based on their RC and Lp-PLA2 levels: low-RC/Lp-PLA2-, high-RC/Lp-PLA2-, low-RC/Lp-PLA2+ and high-RC/Lp-PLA2+. The composite endpoint was a combination of first-ever stroke, myocardial infarction or all-cause mortality. Cox regression analyses were performed to evaluate associations of RC and Lp-PLA2 with composite adverse events. Of the 1864 eligible participants, the average age was 60.6 years, and 74.3% were male. Over a follow-up of 12 years, we identified 500 composite adverse events, including 210 major adverse cardiovascular events and 342 all-cause deaths. When compared with the group of low-RC/Lp-PLA2-, the hazard ratios with 95% confidence intervals in the group of high-RC/Lp-PLA2+ for stroke, myocardial infarction, major adverse cardiovascular event, all-cause death and composite endpoints were 1.37 (0.87-2.16), 0.72 (0.28-1.82), 1.29 (0.85-1.95), 1.61 (1.10-2.38) and 1.43 (1.07-1.91), respectively. A significant interaction between RC and Lp-PLA2 status has been found for all-cause death and composite endpoint (p for interaction <0.05). In addition, joint association of RC and Lp-PLA2 with all-cause death was modified by sex and age of <60 versus ≥60 years (p for interaction: 0.035 and 0.01, respectively). Elevated RC and Lp-PLA2 levels were associated with an increased risk of composite adverse events, with these associations significantly influenced by sex and age. Our study highlights the synergistic effect of RC and Lp-PLA2 on the composite adverse events.

Exploring the impact of graded alcohol use on atherogenic lipid profiles among Latinos with underlying chronic liver disease.

Alcohol use and hepatitis C virus (HCV) often coexist and are associated with cardiovascular disease. One of the underlying drivers is dyslipidemia. We assessed lipid and lipoprotein levels and the relationship between alcohol use and atherogenic lipid profiles, specifically small dense low-density lipoprotein cholesterol (sdLDL-C), in Latinos with and without HCV. From June 1, 2002, to January 1, 2016, 150 Latino adults underwent demographic, clinical, metabolic, lipid/lipoprotein, and genetic evaluations. Linear regression (adjusted for age, sex, and recent alcohol use) assessed factors associated with sdLDL-C. Participant characteristics were as follows: median age 44 years, 64% male, 39% HCV+, and alcohol use in the last 12 months was 19% heavy and 47% moderate. Ancestries were as follows: 52% European, 40% Native American (NA), and 4.3% African. 29% had non-CC PNPLA3, 89% non-CC TM6SF2, and 73% non-CC IL-28b genotypes. High-density lipoprotein (HDL) cholesterol, HDL-3, apolipoprotein A-1, and lipoprotein-associated phospholipase A2 levels differed by alcohol use groups (p < 0.05). On multivariable analysis, female sex (est. -6.08, p < 0.001), HCV+ status (est. -8.49, p < 0.001), and heavy alcohol use (vs. none) (est. -4.32, p = 0.03) were associated with lower, while NA ancestry (est. 0.92; p = 0.01) and adipose tissue insulin resistance (est. 3.30, p < 0.001) were associated with higher sdLDL-C levels. The positive association between NA ancestry and sdLDL-C was dampened by the presence of a non-CC IL28b genotype (interaction est. -1.95, p = 0.01). In this Latino cohort, ancestry and metabolic dysfunction, independent of alcohol use and HCV, were associated with atherogenic risk. In addition to HCV treatment in this population, cardiometabolic health should be optimized.

Effect of moderate wine consumption on the activity of enzymes involved in platelet-activating factor metabolism and thrombotic biomarkers: a randomised, single-blind, parallel, clinical study in CHD men patients.

A randomised parallel intervention study was conducted with male patients diagnosed with CHD. Participants were assigned to three groups: Group A abstained from alcohol (n 20), Group B consumed red wine (n 21) and Group C (n 16) consumed an alcoholic beverage without wine micro-constituents. Biological samples were collected at baseline, 4 and 8 weeks. Enzyme activities of acetyl-CoA:lyso-platelet-activating factor (PAF) acetyltransferase, cytidine 5'-diphospho (CDP)-choline:1-alkyl-2-acetyl-sn-glycerol cholinephosphotransferase (PAF-cholinephosphotransferase), PAF-acetylhydrolase in leukocyte homogenates, serum lipoprotein-associated phospholipase-A2 and plasma markers of thrombosis were measured. PAF-, ADP- and collagen-induced platelet aggregation was measured in human platelet-rich plasma. Red wine consumption led to a 15·3 % reduction in LysoPAF-acetyltransferase activity at 4 weeks (P= 0·008) compared with baseline and Group A (P= 0·01). PAF-cholinephosphotransferase activity was reduced by 11·1 % at 8 weeks (P= 0·04) compared with baseline and by 24·9 % compared with Group C (P= 0·02). PAF-acetylhydrolase activity was reduced by 36·2 % at 8 weeks compared with baseline (P= 0·001) and compared with Group A (P< 0·000) and Group C (P= 0·009). Fibrinogen levels in Group B reduced by 6-9 % at 4 (P= 0·04) and 8 weeks (P= 0·01) compared with baseline while D-dimer in Group C increased by 16·1 % at 8 weeks (P= 0·005) compared with baseline. Platelet aggregation against PAF and collagen was reduced in Group B (82·6 and 35·4 %, respectively), and in Group C (158·4 and 37·1 %, respectively) compared with baseline and Group A (P< 0·05). In conclusion, moderate wine consumption improved the activity of PAF-metabolism enzymes regardless of ethanol and reduced platelet aggregation, probably through mechanisms different from those of ethanol.

Marein alleviates the development of atherosclerosis through targeting miR-126/lipoprotein-associated phospholipase A2 axis.

As a classical precious medicine, Coreopsis tinctoria Nutt. (C. tinctoria) is widely utilized for treatment of cardiometabolic diseases, while the important compound of C. tinctoria, marein exhibits multiple beneficial biological effects that related to the pathophysiological processes underlying atherogenesis. Thus, the purpose of present study is to investigate the role of marein on the development of atherosclerosis. In the current study, we observed that marein exhibited anti-inflammatory response function verified by reduced mRNA and protein levels of classical M1 but enhanced alternative M2 macrophage genes. Moreover, marein dramatically attenuated macrophage-induced foam cell formation with up-regulated cholesterol efflux but down-regulated cholesterol influx-related genes expression in bone marrow-derived macrophage (BMDMs) administrated with oxidized low-density lipoprotein (Ox-LDL), observed by staining with Oil-Red O, RT-PCR, or western blot analysis. Treatment of ApoE knockout mice (ApoE-/-) with marein at indicated time which consistently fed with high-fat diet for 12 weeks was utilized to explore the function of marein on atherogenesis invivo. We revealed that marein-treated group alleviated atherosclerotic plaques in the entire aorta and aortic root and inhibited plaque vulnerability characterized by decreased necrotic core, reduced macrophage, and lipid accumulation, whereas increased fibrous cap, enhanced smooth muscle cell, and collagen deposition. Importantly, we noticed that miR-126 could target to lipoprotein-associated phospholipase A2 (Lp-PLA2), and enhanced miR-126 but reduced Lp-PLA2 expression was responsible for the alleviated function of marein on macrophage dysfunction. Collectively, we identified that marein could be a promising drug for prevention of the development of atherosclerosis by protecting against macrophage-mediated foam cell formation and inflammation, partially through miR-126/Lp-PLA2 dependent mechanism.

Correlation between lipoprotein-associated phospholipase A2 and diabetic peripheral neuropathy in patients with type 2 diabetes mellitus: A cross-sectional study.

Correlation between lipoprotein-associated phospholipase A2 and diabetic peripheral neuropathy in patients with type 2 diabetes mellitus: A cross-sectional study.

A colorectal liver metastasis prediction model based on the combination of lipoprotein-associated phospholipase A2 and serum biomarker levels.

A colorectal liver metastasis prediction model based on the combination of lipoprotein-associated phospholipase A2 and serum biomarker levels.

Exploring Lipoprotein-Associated Phospholipase A2 Levels in Iraqi Patients with Stable Angina: Insights from Coronary Angiography Diagnosis

Stable angina is a prevalent heart disease which can be defined as a clinical syndrome of stable coronary artery disease (CAD) that refers to the presence of myocardial ischemia. Lipoprotein-associated Phospholipase A2 (Lp-PLA2) is an important biomarker of atherosclerosis progression through pro-inflammatory and anti-inflammatory effects. Objective: The aim was to detect the role of Lp-PLA2 in the diagnosis of patients with stable angina and normal left ventricular ejection fraction (LVEF). Patients and methods: The study design was a case-control study. 90 males and females (age 40-76 years) who were presented with chest pain were enrolled in the study, all were subjected to echocardiography, ECG and coronary angiography by the cardiologist. Besides, patient’s questionnaire and biochemical analysis were also used. According to the angiography, they were divided into two groups: 60 patients and 30 as a control group. Levels of Lp-PLA2, total cholesterol, triglycerides (TG), high density lipoprotein-Cholesterol (HDL-C), very low density lipoprotein-Cholesterol (VLDL-C) and low density lipoprotein-Cholesterol (LDL-C) in serum were assessed. The biplane M mode method was used to measure left ventricular ejection fraction (LVEF). Result: It was detected that Lp-PLA2 serum levels were significantly higher in the patients than in the control, (P≤0.01). ROC analysis showed that Lp-PLA2 had specificity of 100% and sensitivity 100%. Conclusion: Measurement of Lp-PLA2 can be applied as an excellent biomarker in the diagnosis of patients with stable angina and normal LV ejection fraction.

Effect of Fibrates on Lipoprotein-associated Phospholipase A2 Mass and Activity: A Systematic Review and Meta-analysis of Controlled Clinical Trials.

In vascular tissue, macrophages and inflammatory cells produce the enzyme lipoprotein- associated phospholipase A2 (Lp-PLA2). Treatment with fibrates decreases Lp-PLA2 levels in individuals with obesity and metabolic syndrome; however, these findings have not been fully clarified. The goal of this study was to investigate the possible effects of fibrate therapy on Lp-PLA2 mass and activity through a meta-analysis of clinical trials. Web of Science, PubMed, Scopus, Google Scholar, and ClinicalTrials.gov databases were searched using MeSH terms and keywords. Randomized controlled trials (RCT) evaluating the effect of statins on Lp- PLA2 mass and/or activity were included in the meta-analysis. Quantitative data were analyzed using a random- effects model and the generic inverse variance method. The meta-analysis of 10 clinical trials indicated that fibrate treatment has no significant effect on Lp- PLA2 mass (fibrate vs. placebo/nothing = WMD: -3.29 ng/ml, 95% CI: -21.35, 14.78, p = 0.72; fibrate vs. active control = WMD: -1.08 ng/ml, 95% CI: -51.38, 49.22, p = 0.97); Lp-PLA2 activity (fibrate vs. active control = WMD: 0.84 nmol/ml/min, 95% CI: -0.17, 1.84, p = 0.10); HDL-LpPLA2 activity (fibrate vs. active control = WMD: 0.77 nmol/ml/min, 95% CI: -0.33, 1.88, p = 0.17); and secretory PLA2 (fibrate vs. active control = WMD: 0.37 ng/ml, 95% CI: -1.22, 1.97, p = 0.65). Also, the results of the sensitivity analysis were robust for all these parameters. In conclusion, fibrate therapy did not reduce the mass and activity of Lp-PLA2.

Potential biomarkers for cerebral small vessel disease with cognitive impairment: a systematic review and meta-analysis.

Cerebral small vessel disease (CSVD) is a common factor in age-related diseases such as stroke and dementia, and about half of dementia patients worldwide are caused by CSVD. CSVD-related cognitive impairment (CSVD-CI) affects more and more elderly people, resulting in economic losses and burdens on families and society. In recent years, circulating biomarkers have made breakthroughs and played an increasingly important role in the diagnosis, progression, and prognosis of CSVD-associated cognitive impairment, and are expected to be applied to the early clinical detection, diagnosis, and treatment of patients with cerebral small vessel disease. Through a systematic review and meta-analysis, this study aimed to assess the relationship between circulating factors and cognitive impairment associated with cerebral small vessel disease, especially the possibility of becoming the potential biomarkers for diagnosis. Articles published before November 2023 were searched in four databases, PubMed, Web of Science, Embase, and Cochrane Library, to identify all relevant studies reporting circulating markers in patients with CSVD. Twenty-nine articles out of 2,911 were finalized for this study. We meta-analyzed 2 or more articles that were jointly considered to be circulating biomarkers of CSVD-CI and summarized a total of 4 possible biomarkers: homocysteine (Hcy), high-sensitivity C-reactive protein (hs-CRP), lipoprotein-associated phospholipase A2 (Lp-PLA2), and neurofilament protein light chain (NfL). The results revealed that patients in the CSVD-related cognitive impairment group had significantly higher levels of Hcy and hs-CRP than those in the CSVD-without cognitive impairment group, whereas there was no statistically significant difference in Lp-PLA2 and NfL between the two groups. Therefore, Hcy, hs-CRP may be considered circulating markers of cognitive impairment associated with cerebral small vessel disease.

Repetitive Transcranial Magnetic Stimulation Combined with Ginkgo Diterpene Lactone Meglumine Injection Recover Cognitive and Neurological Functions of Patients with Acute Ischemic Stroke.

Acute ischemic stroke (AIS) is a prevalent and challenging neurological condition associated with high mortality and morbidity rates. This study aimed to evaluate the therapeutic efficacy of repetitive transcranial magnetic stimulation (rTMS) combined with ginkgo diterpene lactone meglumine injection (GDLMI) on cognitive and neurological function recovery in patients with AIS. A total of 120 patients with AIS, admitted between January 2021 and January 2022, received rTMS combined with GDLMI after admission. Their cognitive and neurological functions were assessed using the Chinese version of the Montreal Cognitive Assessment (MoCA) and the National Institute of Health Stroke Scale (NIHSS) respectively before and after treatment. Additionally, serum levels of lipoprotein-associated phospholipase A2 (Lp-PLA2) and ischemia-modified albumin (IMA) were quantified. Statistical analyses were performed to elucidate potential correlations between Lp-PLA2 and IMA levels and clinical outcomes. After treatment, patients with AIS exhibited significantly improved cognitive and neurological functions, increased MoCA score and decreased NIHSS score compared to those before treatment (p < 0.05). A linear correlation was observed between Lp-PLA2 and IMA levels and the recovery of cognitive function in AIS patients (r = -0.892/-0.764, p < 0.05). Before and after factor adjustment, Lp-PLA2 and IMA were identified as independent influencing factors for the efficiency in cognitive function recovery (p < 0.05). Similarly, Lp-PLA2 and IMA levels were linearly correlated with the recovery of neurological function in AIS patients (r = -0.887/-0.796, p < 0.05). Lp-PLA2 combined with IMA performed better than Lp-PLA2 or IMA alone in predicting the efficiency of rTMS plus GDLMI in promoting the cognitive and neurological function recovery (p < 0.05). rTMS combined with GDLMI can contribute to the cognitive and neurological function recovery in patients with AIS. Serum levels of Lp-PLA2 and IMA could serve as independent influencing factors for the efficiency in promoting cognitive and neurological function recovery.

Predictive Value of Lp-PLA2 Combined with Leukocyte-Derived Markers for Heart Failure After Acute Myocardial Infarction.

We aimed to evaluate the value of lipoprotein-associated phospholipase A2 (Lp-PLA2) in the serum plus leukocyte-derived markers such as platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) for predicting heart failure (HF) after acute myocardial infarction (AMI). A total of 80 AMI patients (case group) hospitalized between June 2019 and July 2022 and 80 healthy subjects (healthy group) were selected. An HF group and a non-HF group were established for the case group. The general data, serum Lp-PLA2 concentration, PLR, and NLR were compared between the two subgroups. Analysis of the risk factors for HF in AMI patients was performed. The case group, compared with the healthy group, had higher serum Lp-PLA2 concentration, PLR, and NLR (p < 0.05). HF occurred in 10 cases (12.50%) in the case group. In comparison to the non-HF group, increases of serum Lp-PLA2 concentration, PLR, and NLR were detected in the HF group (p < 0.05). Elevated se-rum Lp-PLA2 concentration, PLR, and NLR served as risk factors for HF in AMI patients (OR > 1, p < 0.05). NLR, PLR, serum Lp-PLA2, and combination of the three had the areas under the curves of 0.734, 0.731, 0.719, and 0.910, respectively, in predicting HF in AMI patients. NLR, PLR, and serum Lp-PLA2 concentration were elevated in AMI patients, that were associated with HF. Combined determination of NLR, PLR, and serum Lp-PLA2 can effectively predict the risk of HF in AMI patients.

Biochemical Changes and Plasma Level of Lipoprotein-Associated Phospholipase A2 in Patients with and without Coronary Artery Disease: A Cross-Sectional Study

Coronary artery disease (CAD) is the leading cause of death worldwide. the aim of study is to evaluate the association between plasma lipoprotein-associated phospholipase A2 (Lp-PLA2) and the clinical and biochemical risk factors for CAD among Libyan individuals. This cross-sectional study to evaluate plasma concentration of Lp-PLA2 between patients with CAD and those without CAD in both genders based on clinical history, exercise ECG, two-dimensional echocardiography, and coronary angiography. Several biochemical parameters were estimated. Plasma levels of Lp-PLA2 were measured. A total of 181 individuals were recruited for this study, involving 125 with CAD and 56 without CAD. Plasma Lp-PLA2 concentration was significantly higher in patients with CAD versus individuals without coronary artery disease. In addition, the plasma concentration of Lp-PLA2 was higher in patients &gt;60 years of age compared with patients &lt;60 years old. To conclude that Plasma level of Lp-PLA2 concentration was independently correlated with CAD, inflammatory marker such as high sensitivity C-reactive protein among Libyan patients.

Insulin resistance in childhood obesity: The role of dietary habits and their association with novel markers of cardiovascular disease

Background Childhood obesity presents numerous comorbidities such as insulin resistance (IR) and dyslipidemia, and could be associated with alterations in novel markers of cardiovascular (CV) risk like: (1) the activities of associated enzymes such as lipoprotein associated phospholipase A2 (Lp-PLA2) and paraoxonase 1 (PON 1), (2) reverse cholesterol transport (RCT), which comprises cellular cholesterol efflux (CCE), in addition to lecithin:cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) activities, and (3) high density lipoprotein (HDL) antioxidant capacity. Moreover, IR could worsen these cardiometabolic alterations. The objective of the present study was to characterize the effect of IR on novel CV markers in a pediatric population with obesity. Methods Twenty-five obese children and adolescents with IR, and 25 without IR took part in the study. Anthropometric parameters, Tanner stage and dietary habits were registered. Glucose, insulin, non-esterified fatty acid (NEFA), lipid, and high sensitivity C reactive protein (hsCRP) levels, plus Lp-PLA2, LCAT, CETP and PON 1 activities, as well as CCE and HDL antioxidant capacity were measured. A cutoff point of 3.16 in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) determined the presence of IR. Results No differences were observed in age, sex and Tanner stage. Expectedly, the group with IR displayed higher insulin and NEFA levels (p &lt; 0.05). They also presented increased Lp-PLA2 and decreased PON activities (p &lt; 0.05). Importantly, these differences were associated with dietary habits (p &lt; 0.05). Conclusion IR present in pediatric obesity associated with vascular specific inflammation and reduced PON 1 activity, in addition to alterations in glucose metabolism, thus increasing CV risk in adulthood. These proatherogenic disturbances were conditioned by dietary habits.

White Tea Reduces Dyslipidemia, Inflammation, and Oxidative Stress in the Aortic Arch in a Model of Atherosclerosis Induced by Atherogenic Diet in ApoE Knockout Mice.

Objective: In this study, we aimed to evaluate the potential effects of white tea (WT) in the atherosclerosis process characterized by oxidative stress, inflammation, and dyslipidemia. Methods: In our study, apolipoprotein E knockout (ApoE-/-) mice (RRID: IMSR_JAX:002052) and C57BL/6J mice (RRID: IMSR_JAX:000664) were used. In the atherosclerosis model induced by an atherogenic diet (AD), WT was administered via oral gavage at two different concentrations. The animals were sacrificed by decapitation under anesthesia, and their serum and aortic tissues were collected. Total cholesterol (TC), triglyceride (TG), interleukin (IL)-1β, IL-6, IL-10, IL-12, tumor necrosis factor-α (TNF-α), interferon-γ, myeloperoxidase, paraoxonase-1, lipoprotein-associated phospholipase A2, oxidized low-density lipoprotein (Ox-LDL), lectin-like oxidized LDL receptor (LOX-1), a disintegrin, and metalloprotease (ADAM) 10 and 17 activities were determined via colorimetric, enzyme-linked immunoassay, and fluorometric methods. Results: WT supplementation decreased serum Ox-LDL, LOX-1, TC, and TG levels by approximately 50%. TNF- and IL-6 levels were reduced by approximately 30% in the aortic arch. In addition, ADAM10/17 enzyme activities were found to be reduced by approximately 25%. However, no change in the AD-induced fibrotic cap structure was observed in the aortic root. Conclusions: The findings indicate that white tea effectively reduced oxidative stress, inflammation, and dyslipidemia in atherosclerosis but does not affect atheroma plaque morphology.

Association of Lipoprotein-Associated Phospholipase A2 and Lipoprotein(a) With the Risk of Recurrence Stroke in Patients With Acute Ischemic Stroke.

It is still a major global challenge to reduce the high morbidity and mortality of acute ischemic stroke (AIS) and improve the prognosis of patients. This study aims to investigate the prognostic value of lipoprotein-associated phospholipase A2 (Lp-PLA2) combined with lipoprotein(a) (Lp(a)) for long-term stroke recurrence in patients with AIS. This study included 580 patients with AIS. Assessment of Lp-PLA2 and Lp(a) levels was conducted upon patient admission. Continuous monitoring over the long term categorized stroke recurrence as an endpoint. Patients were categorized based on these identified thresholds to compare the risk of stroke recurrence: high Lp-PLA2 and high Lp(a), high Lp-PLA2 and low Lp(a), low Lp-PLA2 and high Lp(a), and low Lp-PLA2 combined with low Lp(a). Among the 580 participants, 101 individuals (17.41%) experienced stroke recurrence within the 2-year follow-up. The majority were male (61.39%), with a median age of 62 years (interquartile range: 55-69.5). Factors independently associated with heightened the risk of recurrence stroke comprised age (hazard ratio [HR], 1.025; p = 0.021), diabetes mellitus (HR, 1.751; p = 0.007), Lp-PLA2 (HR, 1.004; p < 0.001), and Lp(a) (HR, 1.002; p < 0.001). Noteworthy is that the combination of Lp-PLA2 and Lp(a) displayed superior predictive efficacy for long-term stroke recurrence risk in AIS patients compared to individual factors. This investigation underscores the potential advantage of leveraging the combined impact of Lp-PLA2 in conjunction with Lp(a) as a more precise and cost-effective predictive tool for the risk of recurrence stroke in patients with AIS.

The Association of PLA2G7 Gene Polymorphisms with Serum Lp-PLA2 Activity and Lipid Profile in Han Chinese Patients with Coronary Heart Disease.

This study aimed to investigate the distribution patterns of PLA2G7 gene variants in Han Chinese patients with coronary heart disease (CHD), and their relationships with serum lipoprotein-associated phospholipase A2 (Lp-PLA2) levels and lipid profiles. A total of 93han Chinese CHD patients were recruited. Serum Lp-PLA2 levels were determined using enzyme-linked immunosorbent assay (ELISA), while comprehensive analysis of PLA2G7 gene polymorphisms was conducted through whole-exome sequencing. Concurrently, multiple lipid parameters were measured and analyzed. Among these Han Chinese CHD patients, the PLA2G7 gene rs1051931 (c.1136T>C p.Val379Ala) rare variant was highly prevalent (variant rate: 94.62%) among the study population, and showed negative correlation with serum Lp-PLA2 activity. The rs1765208290 (c.233G>A p.Gly78Asp) rare variant showed positive correlation with TG, ApoA, ApoB, HDL, LDL and TCHO levels in the serum. Strong linkage disequilibrium was observed between the rs1805018 (c.593T>C p.Ile198Thr) and rs76863441 (c.835G>T p.Val279Phe), both of which were related to lower Lp-PLA2 activity. In these Han Chinese CHD patients, the rs1051931 (c.1136T>C p.Val379Ala) rare variant in the PLA2G7 gene is closely linked to decreased Lp-PLA2 activity, whereas the rs1765208290 (c.233G>A p.Gly78Asp) rare variant influences lipid homeostasis. The strong LD between rs1805018 (c.593T>C p.Ile198Thr) and rs76863441 (c.835G>T p.Val279Phe) loci may act synergistically to reduce Lp-PLA2 activity.

ADENOSINE IN CARDIOVASCULAR PHYSIOLOGY: MULTIFACETED ROLES IN CORONARY VASODILATION, ATHEROPROTECTION, AND PLATELET REGULATION

This review delves into various aspects of acute coronary syndrome (ACS), emphasizing recent advancements. Despite progress, ACS remains a major global health concern. The classical view linking coronary stenoses to chronic syndrome is challenged, with optimal medical therapy often showing better outcomes. Diverse ACS mechanisms include plaque rupture, calcified nodules, spontaneous dissection of the coronary arteries, and coronary artery spasm. Immune factors, particularly neutrophils and their extracellular traps, play a dual role in both inflammation and tissue healing. The adaptive immune response involving T and B lymphocytes adds complexity. Metabolic and lipid-related factors like adenosine pathways, vitamin D, and lipoprotein-associated phospholipase A2 impact atherothrombotic processes. Non-coding RNAs, including circular, long, and microRNAs contribute to ACS. Genic therapies like Olpasiran and Inclisiran show promise in targeting specific molecular pathways to reduce cardiovascular risk factors. Overall, this review offers a comprehensive understanding of ACS, incorporating recent molecular, immunological, and therapeutic advances, highlighting the need for ongoing research to improve diagnostic and treatment strategies.

Unveiling the Synergy of Serum Lipoprotein-Associated Phospholipase A2 and PLA2G7 Gene Polymorphism (rs1805017) as Key Determinants of Coronary Artery Disease Risk and Severity: Implications for Early Intervention.

Background Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a key enzyme selectively expressed in unstable, rupture-prone atherosclerotic plaques. Previous research has established a strong link between the PLA2G7 gene and the development of coronary artery disease (CAD). While traditional risk factors like cholesterol levels and blood pressure are valuable, there remains a need for more specific biomarkers to identify individuals at heightened risk of atherosclerosis before the onset of clinical symptoms. Our study aimed to investigate the association between serum Lp-PLA2 levels, lipid parameters, cardiac markers, and the rs1805017 variant within the PLA2G7 gene. By exploring these factors, we sought to enhance the assessment of CAD risk and severity. Materials and methods It is a Cross-sectional, case-control study, that recruited 125 subjects, comprising 75 angiographically proven CAD cases and 50 age-sex and ethnically matched controls of a South Indian population. Serum biomarkers were processed according to standard commercial kits.A group of 100 subjects underwent genotyping using Sanger's sequencing method. Results Out of the total study population, 25% of the patients were young men (<45 years). We quantitatively estimated the serum Lp-PLA2 levels and evaluated any possible association of serum Lp-PLA2 levels with all the genotypes of R92H (rs1805017) located on Exon 4 of the PLA2G7 gene on chromosome 6. In CAD patients, we found a significant positive correlation of the lipid profile, Lp(a), hs Troponin I, and Lp-PLA2, but a negative correlation with high-density lipoprotein cholesterol (HDL-C) levels. The genotype frequency distributions of the R92H (rs1805017) polymorphisms were GG (17.9%), GA (35.7%), and AA (46.4%) in the control group, and GG (20.3%), GA (30.4%), and AA (49.3%) in CAD cases. The prevalence of the homozygous genotype and serum Lp-PLA2 levels was highest in patients with triple vessel disease (TVD). After correction, logistic regression showed homozygosity as the main independent risk predictor of CAD (p=0.0087). Receiver operating characteristic (ROC) curves revealed that among all biomarkers tested, Lp-PLA2 showed a higher area under the curve (AUC: 0.935), indicating excellent diagnostic ability with a cutoff >392 ng/ml and a sensitivity of 88.2% and specificity of 90.9% in predicting the risk and severity of CAD. Conclusions Elevated serum Lp-PLA2 levels and homozygosity of rs1805017 were significantly associated with the risk and severity of disease (TVD). Single nucleotide polymorphism (SNP) analysis can be used as a risk stratification test. Alternatively, as elevated Lp-PLA2 is an indicator of unstable rupture-prone plaques, it can be used as an economical, noninvasive risk and severity predictor, especially in places where coronary angiography (CAG) is not available. Although further research is warranted, these findings can assist in primordial prevention or prescribing a prompt therapeutic algorithm to decrease disease mortality.

Diagnostic Utility of Combining Homocysteine, Lipoprotein-Associated Phospholipase A2, and the C-Reactive Protein-to-Albumin Ratio for Assessing Carotid Atherosclerosis and Plaque Stability in Patients with Essential Hypertension.

The objective of this study is to determine the diagnostic utility of combining homocysteine (HCY), lipoprotein-associated phospholipase A2 (LP-PLA2), and the C-reactive protein-to-albumin ratio (CAR) for carotid atherosclerosis (CAS) and plaque stability in patients with essential hypertension (EH). A total of 280 patients with EH were divided into 2 groups according to ultrasound diagnosis: CAS (n = 106) and non-CAS (N-CAS [n = 174]). The CAS group was further segmented into plaque-stable (n = 50) and plaque non-stable (n = 56) groups. General data were collected for all patients. Risk factors associated with CAS and plaque instability in patients with EH, and the diagnostic utility of HCY, LP-PLA2, and CAR testing alone, or in combination, for assessing CAS and plaque instability were determined. Mean age, systolic blood pressure (SBP), duration of EH, smoking, total cholesterol high-density lipoprotein cholesterol, HCY, LP-PLA2 levels, and CAR were higher in the CAS group than those in the N-CAS group (P < 0.05). SBP, duration of EH, HCY and LP-PLA2 levels, and CAR were independent risk factors for CAS (P < 0.05). In addition, HCY, LP-PLA2, and CAR alone demonstrated significant diagnostic efficacy (P < 0.001) but were inferior to the combined diagnostic utility of the 3 parameters (P < 0.001). HCY and LP-PLA2 levels, and CAR were higher in the plaque non-stable than in the plaque-stable group (P < 0.05). Duration of EH, low-density lipoprotein cholesterol, HCY, LP-PLA2, and CAR independently influenced plaque instability in patients with CAS (P < 0.05). The combined diagnostic utility of HCY, LP-PLA2, and CAR (P < 0.001) was superior to that of each parameter alone and demonstrated more pronounced diagnostic efficacy (P < 0.001). HCY, LP-PLA2, and CAR were independent risk factors for CAS and plaque instability in patients with EH. HCY, LP-PLA2, and CAR demonstrated significant diagnostic efficacy for CAS and plaque instability, and combination of the 3 demonstrated the most pronounced diagnostic efficacy.

Lipoprotein-associated phospholipase A2 and its possible association with COPD development: a case-control study

BackgroundThe association of lipoprotein-associated phospholipase A2 (Lp-PLA2) with various cardiovascular events has been well-established. However, the exploration of its potential involvement in Chronic obstructive pulmonary disease (COPD) is currently limited. Therefore, our study aims to examine the relationship between Lp-PLA2 and pulmonary conditions, including emphysema, obstructive ventilatory dysfunction as well as small airway dysfunction, to provide further evidence of a possible association with COPD development.MethodsUsing data from the Southwest Hospital Health Management Center, spanning January 2013 to July 2024, we analyze relationship of serum Lp-PLA2 levels with diffuse pulmonary emphysema and pulmonary functions. In univariate analysis, group differences were assessed with t-tests for numerical variables and Chi-square tests for categorical data. Variables found to be statistically significant (two-sided P < 0.05) in univariate analysis were subsequently included as covariates in multivariate analysis, performed using a binary logistic regression model. Odds ratios and 95% confidence intervals were calculated to assess the differences.ResultsWe established 2 case-control populations: the Imaging population (1056 subjects, mean age 57.666 ± 8.700 years old, 89.9% male) selected from 24,670 initial records, and the Pulmonary Function population (279 subjects, mean age 52.082 ± 11.473 years old, 71.4% male) selected from 1868 initial records. Univariate analysis revealed that serum Lp-PLA2 levels were significantly higher in patients with diffuse pulmonary emphysema, obstructive ventilatory dysfunction as well as small airway dysfunction compared to those without (454.682 ± 141.382U/L vs. 423.330 ± 140.658U/L, P < 0.001; 475.059 ± 157.181U/L vs. 420.824 ± 142.119U/L, P = 0.006; 475.31 ± 148.980U/L vs. 439.036 ± 157.977U/L, P = 0.049, respectively). Multivariate analysis further showed higher Lp-PLA2 levels were associated with increased risks of diffuse pulmonary emphysema, obstructive ventilatory dysfunction as well as small airway dysfunction. Using Lp-PLA2 ≤ 300 U/L as reference, odds ratios for the aforementioned conditions showed a gradually increasing trend with every 100U/L increase in Lp-PLA2 levels.ConclusionsOur preliminary study suggests that Lp-PLA2 is independently associated with diffuse pulmonary emphysema, obstructive ventilatory dysfunction as well as small airway dysfunction, which are commonly seen in COPD development. These findings indicated a possible association between Lp-PLA2 and COPD, though further validation is needed in a large cohort of COPD patients.