LPA Levels Research Articles

Discovery of Potent Selective Nonzinc Binding Autotaxin Inhibitor BIO-32546.

Autotaxin (ATX) is a lysophospholipase D that is the main enzyme responsible for generating LPA in body fluids. Although ATX was isolated from a conditioned medium of melanoma cells, later it was discovered to play a critical role in vascular and neuronal development. ATX has also been implicated in primary brain tumor, fibrosis, and rheumatoid arthritis, as well as neurological diseases such as multiple sclerosis, Alzheimer's disease, and neuropathic pain. As ATX and LPA levels are increased upon neuronal injury, a selective ATX inhibitor could provide a new approach to treat neuropathic pain. Herein we describe the discovery of a novel series of nonzinc binding reversible ATX inhibitors, particularly a potent, selective, orally bioavailable, brain-penetrable tool compound BIO-32546, as well as its synthesis, X-ray cocrystal structure, pharmacokinetics, and in vivo efficacy.

Association of lipoprotein a in early pregnancy with gestational diabetes mellitus: a prospective cohort study

Objective: To investigate the association of lipoprotein a (Lpa) in early pregnancy with gestational diabetes mellitus (GDM) risk. Methods: A total of 445 pregnant women in 12-14 gestational weeks from "Maternal Key Nutritional Factors and Offspring's Atopic Dermatitis" cohort were included in this study. The demographic characteristics of participants were collected by using questionnaires, and the fasting glucose and lipids levels in early pregnancy were measured. The results of oral glucose tolerance test (OGTT) between 24-28 gestational weeks were recorded. Multivariate logistic regression model was applied to analyze the association of Lpa with GDM by calculating the OR and 95%CI after adjustment for covariates. Results: The incidence number of GDM was 78 (17.5%). The Lpa level in pregnant women with GDM was significantly higher than that in pregnant women without GDM [105.5 (92.0, 122.0) vs. 97.0 (87.0, 109.0) mg/L], P<0.05. Lpa was significantly associated with GDM risk [OR (95%CI) =1.21(1.08-1.36) per 10 mg/L], P<0.05. The association was still significant after adjustment for covariates including age, gestational weeks et al, the adjusted OR was 1.14 (95%CI: 1.01-1.30), P=0.03. Conclusions: The elevation of Lpa in early pregnancy is one of risk factor for GDM. Maintaining normal Lpa level during early pregnancy can benefit early prevention of GDM and offspring health.

Association Between Serum Lipid Levels and Patients With Primary Angle-Closure Glaucoma in China: A Cross Sectional, Case–Control Study

Objective: To evaluate the serum lipid levels of patients with primary angle-closure glaucoma (PACG) and to investigate the relationship between serum lipid levels and PACG.Methods: In this cross-sectional, case–control study, a total of 320 PACG subjects and 242 age- and sex-matched control subjects were recruited. Serum high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), small dense LDL-C (SDLDL-C), triglyceride (TRIG), and cholesterol (CHOL) levels were measured using enzymatic colorimetry. Serum apolipoprotein A (APOA), apolipoprotein B (APOB), apolipoprotein E (APOE), and lipoprotein(a) (LPa) levels were measured by immunoturbidimetry.Results: The serum LDL-C, TRIG, HDL-C, APOE, LPa, CHOL, APOB, and APOA levels were significantly higher (p < 0.05) in the PACG group than in the control group. Multiple liner regression analyses revealed that there was a statistically correlation between HDL-C levels and mean deviation MD (B = 0.389, P = 0.002, 95% confidence interval [CI] = −1.249 to −0.624); LDL-C levels and MD (B = 0.190, P = 0.019, 95% CI = −5.632 to −1.306); and CHOL levels and MD (B = 0.364, P = 0.27, 95% CI = −7.727 to −1.839). Logistic regression analyses showed that high serum HDL-C (odds ratio [OR] = 11.01, 95% CI = 5.616–21.587), LDL-C (OR = 1.330, 95% CI = 1.079–1.640), SDLDL-C (OR = 1.007, 95% CI = 1.005–1.008), APOA (OR = 13.621, 95% CI = 7.251–25.591), APOB (OR = 2.243, 95% CI = 1.060–4.732), LPa (OR = 0.999, 95% CI = 0.998–1.00), and CHOL (OR = 1.131, 95% CI = 1.005–1.326) levels were significantly associated with PACG.Conclusions: High serum HDL-C, LDL-C, APOA, APOB, LPa, and CHOL levels were associated with PACG.

Suppressing postcollection lysophosphatidic acid metabolism improves the precision of plasma LPA quantification

AbstractLysophosphatidic acid (LPA) is a potent signaling lipid, and state-dependent alterations in plasma LPA make it a promising diagnostic marker for various diseases. However, plasma LPA concentrations vary widely among reports, even under normal conditions. These variations can be attributed, at least in part, to the artificial metabolism of LPA after blood collection. Here, we aimed to develop an optimized plasma preparation method that reflects the concentration of LPA in the circulating blood. The main features of the devised method were suppression of both LPA production and degradation after blood collection by keeping whole blood samples at low temperature followed by the addition of an autotaxin inhibitor to plasma samples. Using this devised method, the LPA level did not change for 30 min after blood collection. Also, human and mouse LPA levels were found to be much lower than those previously reported, ranging from 40 to 50 nM with minimal variation across the individual. Finally, the increased accuracy made it possible to detect circadian rhythms in the levels of certain LPA species in mouse plasma. These results demonstrate the usefulness of the devised plasma preparation method to determine accurate plasma LPA concentrations.

PMS46 New HIP-Worn Accelerometer in Testing Hungarian Population's Physical Activity Patterns, RM42 in the Eupasmos Project

The RM42 is a triaxial hip-worn accelerometer, suitable to measure physical activity (PA) level, movements, sitting time and sleeping quality. We aimed to test the tool on Hungarian sample and present the preliminary data of the EUPASMOS project. The study comprised 546 participating adults (228 males and 318 females), during February-May 2019 using quota sampling by age and gender representing the Hungarian adult population. PA was measured by RM 42 for 7 consecutive days. Data were presented as median (IQR), using SPSS 24, where level of significance was set at p<0.05. Mann-Whitney U Test and Kruskal Wallis Test were used. Females took 5926 (4808-7506), males 6869 (4760-10067) steps daily. Respondents spent 8.33 to 8.50 hours [M 500.00 (432.25-555.00), F 510.00 (440.00-598.50) min/day] sedentary per day, 10.50 to 12.25 hours [F 630 (420-903), M 735 (599-1130) min/week] with standing and 5.25-7.58 hours [M 315 (210-432), F 455 (147-588) min/week] with moderate PA (MPA) per week. Light PA was more characteristic with 28 weekly hours [F 1673 (1480-1960), M 1663 (1437-1901) min/week]. Vigorous PA (VPA) could be only described in the 18-35 male [7.00; (0.00-36.75) min/week] and 35-49 female [14.00; (0.00-49.00) min/week] age group. Significant gender difference was found between steps and sitting (p=0.022, p=0.033 respectively). The level of LPA, MVPA and VPA and the number of steps as well significantly decreased with age (p=0.001, p<0.001, p<0.001, p<0.001 respectively). The first Hungarian examination using RM42 could be considered successful. More accurate description on light PA could be given. Low level of VPA can be explained by the lack of sport, which requires interventions. However, a population-based representative study is needed to confirm this assumption.

The relation of LP(A) and vitamin D as independent factors with HBA1C levels in patients with type 2 diabetes mellitus

Background and Aims: Lp(a) is a potent, highly heritable risk factor for atherosclerotic and cardiovascular disease(ASCVD).Several studies have correlated elevated Lp(a) levels with an increased risk of DMT2 The study focuses on the correlation between Lpa and VitaminD3 levels with HbA1c in patients with DMT2 who are on optimal antidiabetic treatment (insulin+/-tablets).The study involved 108 DMT2 patients,(51 males,57 females),with an average age of 78.2±10y.o. Lipid profile,VitD and HbA1c levels were measured at 3,9 and 12 months.

Effects of Chemotherapy on Serum Lipids in Chinese Postoperative Breast Cancer Patients.

PurposeChemotherapy is a comprehensive therapy for breast cancer; nevertheless, its associated adverse effects are drawing increasing attention with the continuous improvement of the efficacy. The changes in serum lipids of breast cancer patients caused by chemotherapy have been reported by previous studies, whereby the former increase the incidence rate of cardiovascular disorders. However, the variations in the changes of serum lipids with different chemotherapy regimens have seldom been reported.MethodsFrom January 2011 to December 2017, 1740 breast cancer patients treated with chemotherapy were recruited at the First Affiliated Hospital of Nanjing Medical University. The chemotherapy regimens included anthracycline-based, taxane-based, and anthracycline-plus-taxane-based regimens, dose-dense and standard-interval regimens. Lipid profiles that contained TG (triglyceride), TC (total cholesterol), HDL-C (high-density lipoprotein cholesterol), LDL-C (low-density lipoprotein cholesterol) and Lpa (lipoprotein a) levels were collected prior to the first, second and last cycles of chemotherapy. The changes of serum lipids with the same or different chemotherapy regimens were analyzed and compared.ResultsIt was observed that the levels of TG, TC, LDL-C and Lpa increased significantly while that of HDL-C decreased after adjuvant chemotherapy in breast cancer patients (P<0.05). Besides, dose-dense regimens had more influence in TG and HDL-C and less influence in TC and LDL-C than standard-interval regimens. HDL-C was more sensitive to anthracycline-based regimens than taxane-based regimens. The level of TG with anthracycline-plus-taxane-based regimens was higher than that with only anthracycline-based or taxane-based regimens, and the level of HDL-C with anthracycline-plus-taxane-based regimen showed lower than that with taxane-based regimen.ConclusionIn summary, this study proposed that dyslipidemia was strongly associated with chemotherapy in Chinese breast cancer patients after operative treatment. Furthermore, the changes in levels of serum lipids varied among patients with different chemotherapy regimens and taxane had less effect on dyslipidemia than anthracycline.

Association between Very Low-Density Lipoprotein Cholesterol (VLDL-C) and Carotid Intima-Media Thickness in Postmenopausal Women Without Overt Cardiovascular Disease and on LDL-C Target Levels.

Background: atherosclerotic process inexorably advances in patients reaching low-density lipoprotein cholesterol (LDL-C) targets. An attractive hypothesis is that lipoprotein particles (very low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL)), could contribute to residual risk. The present study aims to investigate the relationship between carotid intima-media thickness (IMT) and different lipoprotein subfractions in a cohort of healthy postmenopausal women. Methods: 75 postmenopausal women, at LDL-C target levels without overt cardiovascular disease, underwent biochemical analyses (including subfraction assay of plasma lipoproteins) and carotid ultrasound examination. Results: a statistically significant correlation between VLDL and carotid IMT (p < 0.001) was found. No significant correlation was found between carotid IMT and LDL-C (p = 0.179), IDL-C (p = 0.815), high-density lipoprotein (HDL) (p = 0.855), and LDL score (p = 0.240). Moreover, IMT is significantly correlated to LDL particle diameter (p = 0.044). After adjusting for age, systolic blood pressure, body mass index, smoking habits, glucose plasma concentration, and Lipoprotein(a) (Lpa) levels, multivariate analysis showed that women in the third tertile of VLDL-C, compared with those in the first tertile, were significantly associated to the highest IMT (p = 0.04). Conclusions: in this cohort of postmenopausal women, VLDL-C was significantly associated to carotid IMT, independent of main cardiovascular risk factors. These findings pave the way for targeting circulating concentrations of VLDL-C to reduce cardiovascular events in patients with target LDL-C levels.

Comparing Primary Prevention Recommendations: A Focused Look at United States and European Guidelines on Dyslipidemia.

Comparing Primary Prevention Recommendations: A Focused Look at United States and European Guidelines on Dyslipidemia.

Effect of proprotein convertase subtilisin/kexin type 9 inhibitor on blood lipid profile in patients with extremely high risk atherosclerotic cardiovascular disease

To investigate the lowering effect on lipid and safety of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor in patients with extremely high risk atherosclerotic cardiovascular disease (ASCVD). The outpatients and in-patients with extremely high risk ASCVD admitted to the Second Affiliated Hospital of Chongqing Medical University from April to October in 2019 were enrolled. The enrolled patients were divided into two groups by random number table method. The patients in the atorvastatin group were given only 20 mg atorvastatin orally every night for 4 weeks. In the combined group, oral atorvastatin was administered with subcutaneous injection of 140 mg evolocumab, a PCSK9 inhibitor, once every 2 weeks, and the course of treatment was 4 weeks. Serum lipid profile was measured before and 4 weeks after treatment, including triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and lipoprotein-a (Lp-a). Adverse events were recorded. During the study period, a total of 40 patients were enrolled, with 20 patients in the atorvastatin group and 20 in the combined group. There was no significant difference in blood lipid profile before treatment between the two groups. After 4 weeks of treatment, the levels of TC and LDL-C in the two groups and Lp-a level in the combined group were significantly lower than those before treatment, while the levels of TG and HDL-C in the two groups were not statistically significant. Further analysis showed that the differences in TC, LDL-C and Lp-a between before and after treatment in the combined group were significantly higher than those in the atorvastatin group [TC difference (mmol/L): 2.78±1.98 vs. 0.54±0.83, LDL-C difference (mmol/L): 1.91±1.38 vs. 0.39±0.72, Lp-a difference (mg/L): 115.87±138.93 vs. -84.19±251.85, all P < 0.05]. Only 1 patient in the combined group developed allergic reaction, mainly manifested as skin rash, who alleviated after anti-allergic treatment. No other adverse reactions such as abnormal liver function and increased myozyme occurred in the two groups. PCSK9 inhibitor could rapidly and effectively reduced the levels of TC, LDL-C and Lp-a in extremely high risk ASCVD patients, while had little effect on the levels of TG and HDL-C. It is safe to some extent.

The Status of Inflammatory Factors Involved in Coronary Artery Disease in Veteran Football Players

Background: Homocysteine, C-reactive protein (CRP), fibrinogen, and lipoprotein (a) (LPA) are four novel cardiovascular risk factors. Objectives: The purpose of this study was to compare the serum levels of these substances in veteran football players and non-athletes. Methods: The subjects of this study were 16 male orthopedic veterans assigned to the two control and experimental groups. The age range was 40 to 50 years old. The athlete group was players of North Khorasan veterans’ team of futsal that trained regularly in the past six months. Trainings of the athlete group were three sessions per week that each session consisted of a warm-up, technical, tactical, and fitness trainings and cooling down. Non-athlete subjects had no regular trainings in the past six months. After 12 hours of fasting, serum levels of dependent variables were evaluated. Independent t-test was used for computing the mean differences of dependent variables between the two groups. Results: The findings showed that mean levels of homocysteine (P = 0.034), fibrinogen (P = 0.001) and LPA (P = 0.022) were lower in the experimental group compared to the control group (P ≤ 0.05). There was no significant difference between the two groups in terms of CRP mean levels (P = 0.072). Conclusions: Generally, orthopedic veterans can prevent cardiac events through regular futsal training because this type of training may reduce the levels of homocysteine, fibrinogen and LPA.

Abstract 605: Association of blood lipid profile and lung cancer risk: Results from the Southern Community Cohort Study

Abstract Lung cancer is the second most common cancer and the leading cause of cancer death in the U.S. African Americans (AAs) have a higher incidence rate than any other racial group. Lipid metabolism and homeostasis play important roles in the growth of cancer cells and the regulation of membrane proteins. Some previous epidemiological studies have evaluated the association between blood lipid levels and lung cancer risk; however, the results were inconsistent, and few explored patterns among AAs. To investigate the association of blood lipid levels and lung cancer risk, particularly in a low socioeconomic population and AAs, we conducted a nested case-control study using resources from the Southern Community Cohort Study, a well-characterized prospective cohort study of approximately 86,000 adult men and women, two-thirds of whom are AAs. Blood lipid profiles, including total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TRIG), and lipoprotein-a (Lp-a), were measured in 372 lung cancer cases and 721 matched controls. AAs had lower median levels of TRIG, and higher levels of HDL and Lp-a than European Americans (EAs). Conditional logistic regression analysis revealed an inverse association between TC and lung cancer risk, with an adjusted OR for the highest vs. lowest tertiles of 0.67 (95% CI: 0.45-0.99). This association was observed in both AAs and EAs, but was only statistically significant in EAs. Further stratified analysis found that this association was only significant in cases that were diagnosed within 2 years of blood collection. No significant associations of other lipid markers with lung cancer risk were observed. The findings from our study suggest that the inverse associations between TC and lung cancer risk more likely resulted from cancerous occurrence and progression and associated lifestyle changes rather than being indicative of causal markers. Citation Format: Yan Sun, Jie Wu, Hyung-Suk Yoon, Wei Zheng, William J. Blot, Qiuyin Cai. Association of blood lipid profile and lung cancer risk: Results from the Southern Community Cohort Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 605.

Screening a Resource of Recombinant Protein Fragments for Targeted Proteomics.

The availability of proteomics resources hosting protein and peptide standards, as well as the data describing their analytical performances, will continue to enhance our current capabilities to develop targeted proteomics methods for quantitative biology. This study describes the analysis of a resource of 26,840 individually purified recombinant protein fragments corresponding to more than 16,000 human protein-coding genes. The resource was screened to identify proteotypic peptides suitable for targeted proteomics efforts, and we report LC-MS/MS assay coordinates for more than 25,000 proteotypic peptides, corresponding to more than 10,000 unique proteins. Additionally, peptide formation and digestion kinetics were, for a subset of the standards, monitored using a time-course protocol involving parallel digestion of isotope-labeled recombinant protein standards and endogenous human plasma proteins. We show that the strategy by adding isotope-labeled recombinant proteins before trypsin digestion enables short digestion protocols (≤60 min) with robust quantitative precision. In a proof-of-concept study, we quantified 23 proteins in human plasma using assay parameters defined in our study and used the standards to describe distinct clusters of individuals linked to different levels of LPA, APOE, SERPINA5, and TFRC. In summary, we describe the use and utility of a resource of recombinant proteins to identify proteotypic peptides useful for targeted proteomics assay development.

Lysophosphatidic acid levels in cerebrospinal fluid and plasma samples in patients with major depressive disorder

Major depressive disorder (MDD) is the most common psychiatric disorders. However, a biochemical marker has yet to be established for clinical purposes. It is proposed that lysophosphatidic acid (LPA, 1-acyl-2-sn-glycerol-3-phosphoate) plays some important roles in emotional regulation of experimental animals. Therefore, in this study, we measured LPA levels using enzyme-linked immunosorbent assays of cerebrospinal fluid (CSF) and plasma samples from patients with MDD. The participants were 52 patients and 49 normal healthy controls for CSF study, and 47 patients and 44 controls for plasma study. We used the Japanese version of the GRID Hamilton Depression Rating Scale (17-item version) for the assessment of depressive symptoms. We found no associations between LPA levels (CSF or plasma) and either diagnosis or severity of MDD, or with psychotropic medication. In conclusion, our data suggest that LPA levels likely would not serve as a practical biomarker of MDD.

Association of lipoprotein a, fibrinogen and D-dimer with vascular cognitive impairment in patients with ischemic cerebral small vessel diseases

Objective To explore the correlation between lipoprotein a (Lpa), fibrinogen (FIB) and D-dimer (D-D) and vascular cognitive impairment in patients with ischemic cerebral small vessel diseases (CSVD). Methods Totally 300 patients with ischemic CSVD who were admitted to the Department of Neurology, Affiliated Hospital of North China University of Science and Technology were selected as the research objects, and 70 healthy outpatients in the same period were selected as the control group.Cognitive function was assessed with Mini Mental State Examination(MMSE). According to the results of MMSE, patients with ischemic CSVD were divided into cognitive normal group (106 cases) and cognitive impairment group (194 cases). The cognitive impairment group was further divided into mild cognitive impairment group (100 cases), moderate cognitive impairment group (60 cases) and severe cognitive impairment group (34 cases). Lpa level was detected by latex immunoturbidimetry, FIB level by coagulation and D-D level by ELISA.The results were compared and analyzed. Results (1) Compared with the control group (Lpa: (101.67±37.37)mg/L, FIB: (3.02±0.67) g/L, D-D: (231.49±95.00) mg/L), the levels of Lpa, FIB and D-D in normal group(Lpa: (150.58±89.55) mg/L, FIB: (3.48±0.80) g/L, D-D: (287.79±125.25)mg/L)and cognitive impairment group(Lpa: (257.98±189.23)mg/L , FIB: (3.86±0.97) g/L, D-D: (347.23±120.69) mg/L)increased significantly (all P<0.01). Compared with the cognitive normal group, the levels of Lpa, FIB and D-D in cognitive impairment group increased significantly (all P<0.01). (2) Compared with mild cognitive impairment group (Lpa: 169.08±51.63 mg/L, FIB: (3.10±0.69)g/L, D-D: (288.91±92.58)mg/L), the levels of Lpa, FIB and D-D of in moderate cognitive impairment group (Lpa: (236.78±107.15) mg/L, FIB: (3.52±0.67) g/L, D-D: (345.03±132.68) mg/L), severe cognitive impairment group (Lpa: (292.65±108.19) mg/L, FIB: (4.04±1.08) g/L, D-D: (401.58±84.87) mg/L) increased significantly (all P<0.01). Compared with the moderate cognitive impairment group, the levels of Lpa, FIB and D-D in the severe cognitive impairment group increased significantly (all P<0.01). (3) The ROC curve was fitted with cognitive impairment as state variable.The area under the ROC curve of Lpa was 0.706, P<0.01, 95% CI was (0.646-0.766), the area under the ROC curve of FIB was 0.613, P=0.001, 95% CI was (0.548-0.679), and the area under the ROC curve of D-D was 0.670, P<0.01, 95% CI was (0.604-0.736). (4) Lpa, FIB and D-D were positively correlated with the degree of cognitive impairment in patients with ischemic cerebral small vessel diseases (rLpa=0.522, P<0.01; rFIB=0.410, P<0.01; rD-D=0.488, P<0.01). Conclusion Serum Lpa, FIB and D-D are closely related to the degree of vascular cognitive impairment and cognitive impairment in patients with ischemic CSVD, which may be involved in the occurrence and development of cognitive impairment.Detection of serum levels of Lpa, FIB and D-D is of great clinical value in the early diagnosis, assessment and treatment of cognitive impairment in ischemic CSVD. Key words: Ischemic cerebral small vessel diseases; Vascular cognitive impairment; Lipoprotein a; Fibrinogen; D-dimer

Associations between plasma lysophospholipids concentrations, chronic kidney disease and the type of renal replacement therapy

BackgroundLysophosphatidic acid (LPA) and lysophosphatidylcholine (LPC) are bioactive lysophospholipids involved in the pathogenesis of renal diseases, especially the renal fibrosis. Plasma LPC concentrations in chronic kidney disease (CKD) patients are lower or similar to those observed in control groups, but less is known about the LPA concentrations. The main aim of the study was the analysis of associations of chronic kidney disease and renal replacement therapy with the plasma LPA concentrations. We have also analyzed the relationship between the plasma concentrations of LPA and LPC.Material and methodsStudy group consisted of 110 patients with CKD in stages G3-G5 according to the KDIGO guidelines and was divided into four subgroups: treated conservatively (CT, 30 patients), on hemodialysis (HD, 30 patients), on peritoneal dialysis (PD, 30 patients) and renal transplant recipients (RT, 20 patients). In HD the blood was collected immediately before (HD D1) and after the dialysis (HD D2). In RT the blood was collected immediately before (RT D1) and 3–14 days after the transplantation (RT D2). The control group (Con) consisted of 50 healthy volunteers. Plasma concentrations of LPA and LPC were measured using enzyme-linked immunosorbent assays.ResultsIn CT, PD and RT D2 plasma concentrations of LPA were significantly higher, compared to Con. In HD, LPA levels did not differ compared to Con and they were significantly lower compared to PD (HD D1 and HD D2), RT D2 (HD D1 and HD D2) and CT (HD D1). However, in most of patients concentrations of LPA were within the range of reference values established in healthy volunteers. Concentrations of LPC were significantly lower in almost all patients subgroups, compared to Con, except in PD. There were no significant correlations between plasma concentrations of LPA and LPC in any of patients subgroups.ConclusionsPresence of CKD is associated with increased plasma LPA levels and the hemodialysis therapy reduces this influence. However, only in a small percentage of patients with CKD, LPA concentrations are out of the reference range, which makes LPA not useful as a diagnostic marker for CKD. Further studies are needed to confirm and explain observed relationships.

Autotaxin/lysophosphatidic acid signaling mediates obesity-related cardiomyopathy in mice and human subjects.

Obesity is associated with increased cardiovascular morbidity and mortality, but the direct signals to initiate or exaggerate cardiomyopathy remain largely unknown. Present study aims to explore the pathophysiological role of autotaxin/lysophosphatidic acid (LPA) in the process of cardiomyopathy during obesity. Through utilizing mouse model and clinical samples, present study investigates the therapeutic benefits of autotaxin inhibitor and clinical correlation to obesity‐related cardiomyopathy. The elevated circulating levels of autotaxin are closely associated with cardiac parameters in mice. Administration with autotaxin inhibitor, PF‐8380 effectively attenuates high fat diet‐induced cardiac hypertrophy, dysfunction and inflammatory response. Consistently, autotaxin inhibition also decreases circulating LPA levels in obese mice. In in vitro study, LPA directly initiates cell size enlargement and inflammation in neonatal cardiomyocytes. More importantly, circulating levels of autotaxin are positively correlated with cardiac dysfunction and hypertrophy in 55 patients. In conclusion, present study uncovers the correlation between circulating autotaxin and cardiac parameters in mice and human patient, and provided solid evidence of the therapeutic application of autotaxin inhibitor in combating obesity‐related cardiomyopathy.

Inflammation markers in coronary heart disease patients with aortic valve stenosis

Raised level of lipoproteide (a) (Lpa) is an independent risk factor of coronary heart disease (CHD) and is also a monogenic predictor (there is growth of prevalence) of aortic stenosis (AS) with the increase of Lpa in population. Lysophosphatide acid, secreted by an enzyme with phospholipase D activity — autotaxin (ATX) is an inflammatory mediator. Humoral immunity involvement in inflammatory processes in coronary arteries and aortic valve might present with the presence of circulating autoantibodies and shifts in the values of cellular immunity.Aim.To assess the relation of Lpa, ATX and immunity with the presence of AS in chronic CHD patients.Material and methods.To a single moment study, 210 patients were included, with chronic CHD. Patients were selected to two groups by the presence (main group, n=47) or absence (controls, n=163) of degenerative AS by echocardiography. Patients were taking standard CHD therapy. All patients underwent clinical blood count, lipids concentration and Lpa. ATX, C-reactive protein, autoantibodies to ApoB-100 lipoproteides and their Cu2+-oxidated modifications. Phenotypes of apoprotein (a) were assessed in 168 patients.Results.CHD patients with degenerative AS were older (74,2±7,8 versus 67,6±9,4 y., p=0,0007), but did not differ by the clinical and biochemical characteristics, level of Lpa and high sensitive С-reactive protein (hsCRP). Concentration of АТХ in plasma was significantly higher (554±95 and 497±105 ng/mL, p=0,001), but the level of IgM autoantibodies against the oxidated lipoproteid (а) (oxLpa) — significantly lower (10,8 [7,9;15,1] and 13,4 [11,4;16,7] relative units, p&lt;0,001) in the main group comparing to control. Neutrophilic-lymphocytal index also differed significantly in the AS group and non-AS (2,04 [1,56;3,14] and 1,72 [1,39;2,14]). By the results of logistic analysis, the age, level of ATX, titer of autoantibodies to oxLpa and neutrophilic-limphocytal index were significant independent predictors of the degenerative AS.Conclusion.In the patients with chronic CHD, undergoing statin therapy, the levels of ATX, autoantiboides IgM against the oxLpa and relation of neutrophils to lymphocytes, but not the concentration of Lpa and low molecular phenotype of apo(a), were related to AS presence.

RAISED LEVEL OF LIPOPROTEIDE(A) AS A PREDICTOR OF CARDIOVASCULAR COMPLICATION POST REVASCULARIZATION OF THE LOWER ExTREMETIES ARTERIES

Aim. Lipoproteide (a) (Lpa) is a pathogenetic risk factor of cardiovascular atherosclerotic disease. On the role of Lpa in the development of cardiovascular complications (CVC) after lower limbs arteries revascularization, there is lack of data. The aim of the study was assessment of Lpa relation to CVC occurrence after revascularization of lower extremities during 1 year follow-up.Material and methods. In the study, 111 patients were included (97 males, 14 females, mean age 66±9 y.o.), who had undergone revascularization of lower libms arteries due to atherosclerosis. As CVC during 1 year follow-up, the following were taken: recurrent intermittent claudication, lower extremity amputation, ischemic stroke, transient cerebral ischemia, non-fatal myocardial infarction, unstable angina, repeat revascularization and cardiovascular death. In all patients, in the blood serum, there were measured lipids and Lpa.Results. Within 1 year after revascularization there were 45 (41%) CVC. In the group with raised Lpa ≥30 mg/dL there were more CVC than in Lpa &lt;30 mg/dL: relative risk 2,1 (95% CI 1,3-3,5; p=0,004). Hence the increased level of Lpa is an independent predictor of CVC after revascularization of lower extremities arteries.Conclusion. In prospective study, during 1 year after revascularization the level of Lpa ≥30 mg/dL is associated with double increase of the risk of CVC.

Lipoprotein(a) accelerated the progression of atherosclerosis in patients with end-stage renal disease

BackgroundIncreased plasma level of lipoprotein(a) (Lpa) is a risk factor of cardiovascular diseases. This study aimed to explore the role of Lpa in the progression of atherosclerosis in patients with end-stage renal disease (ESRD) and to investigate whether its potential mechanism is mediated by CXC chemokine ligand 16 (CXCL16) and low-density lipoprotein receptor (LDLr).MethodsThis is a retrospective clinical study. From January 2015 to April 2016, forty-six ESRD patients from Danyang First People’s Hospital were investigated. The patients were grouped according to their plasma Lpa levels: control group (Lpa < 300 mg/l, n = 23) and high Lpa group (Lpa ≥ 300 mg/l, n = 23). ESRD Patients with acute infective diseases, cancer, and/or chronic active hepatitis were excluded. Biochemical indexes and lipid profiles of the patients were measured. Surgically removed tissues from the radial arteries of ESRD patients receiving arteriovenostomy were used for the preliminary evaluation of atherosclerosis. Haematoxylin-eosin (HE) and filipin staining were used to observe foam cell formation. Protein expression levels of Lpa, CXCL16, and LDLr were detected by immunohistochemistry staining and immunofluorescent staining.ResultsThere was more foam cell formation and cholesterol accumulation in the radial arteries of the high Lpa group than in those of the control group. Furthermore, the expression levels of Lpa, CXCL16, and LDLr were significantly increased in the radial arteries of the high Lpa group. Correlation analyses showed that the protein expression levels of Lpa (r = 0.72, P < 0.01), LDLr (r = 0.54, P < 0.01), and CXCL16 (r = 0.6, P < 0.01) in the radial arteries of ESRD patients were positively correlated with the plasma Lpa levels. Further analyses showed that the co-expression of Lpa with LDLr or CXCL16 was increased in the high Lpa group.ConclusionsHigh plasma Lpa levels accelerated the progression of atherosclerosis in ESRD through inducing Lpa accumulation in the arteries, which was associated with LDLr and CXCL16. These two lipoproteins could both be major lipoprotein components that regulate the entry of Lpa into arterial cells.