A family of eukaryotic lysophospholipid acyltransferases with broad specificity

The budding yeast ALE1 gene encodes a lysophospholipid acyltransferase (LPLAT) with broad specificity. We show that yeast LPLAT (ScLPLAT) belongs to a distinct protein family that includes human MBOAT1, MBOAT2, MBOAT4, and several closely related proteins from other eukaryotes. We further show that two plant proteins within this family, the Arabidopsis proteins AtLPLAT1 and AtLPLAT2, possess lysophospholipid acyltransferase activities similar to ScLPLAT. We propose that other members of this protein family, which we refer to as the LPLAT family, also are likely to possess LPLAT activity. Finally, we show that ScLPLAT differs from the specific lysophosphatidic acid acyltransferase that is encoded by SLC1 in that it cannot efficiently use lysophosphatidic acid produced by acylation of glycerol-3-phosphate in vitro.     

Immediate versus staged revascularisation of non-culprit arteries in patients with acute coronary syndrome: a systematic review and meta-analysis

Although there is robust evidence that revascularisation of non-culprit vessels should be pursued in patients presenting with an acute coronary syndrome (ACS) and multivessel coronary artery disease (MVD), the optimal timing of complete revascularisation remains disputed. In this systematic review and meta-analysis our results suggest that outcomes are comparable for immediate and staged complete revascularisation in patients with ACS and MVD. However, evidence from randomised controlled trials remains scarce and cautious interpretation of these results is recommended. More non-biased evidence is necessary to aid future decision making on the optimal timing of complete revascularisation.Supplementary InformationThe online version of this article (10.1007/s12471-022-01687-7) contains supplementary material, which is available to authorized users.     

Comparison of temporal changes in established cardiovascular biomarkers after acute coronary syndrome between Caucasian and Chinese patients with diabetes mellitus

Abstract

Background: Population means of conventional cardiovascular biomarkers are known to differ between ethnic groups. In this study we performed detailed comparisons in the temporal pattern of these biomarkers between Caucasian and Chinese diabetic patients with acute coronary syndrome (ACS).

Methods: We studied differences in temporal changes of established cardiovascular biomarkers, including high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol, cardiac Troponin T (TnT), NT-proBNP and C-reactive protein (CRP), in 48 Chinese and 48 clinically matched Caucasian patients with type 2 diabetes mellitus who were admitted for ACS. Blood samples were collected at regular time intervals during 30?days to 1?year after the index ACS.

Results: In the >30?day post ACS period, mean serum levels of LDL (2.16 vs. 1.47?mmol/L; p-value <0.001), total cholesterol (4.08 vs. 3.11?mmol/L; p-value <0.001), TnT (11.0 vs. 7.76?ng/L; p-value 0.010) and CRP (2.0 vs. 0.78?mg/L; p-value <0.001) were systematically higher in Caucasian than in Chinese patients. HDL and NT-proBNP levels were similar.

Conclusions: Our study showed clinically relevant differences in levels of established cardiovascular biomarkers between Caucasian and Chinese post ACS patients. Further cross-ethnic studies are warranted to determine secondary prevention treatment biomarker targets in specific populations.     

双联抗血小板治疗急性冠脉综合征临床疗效观察

目的:探讨双联抗血小板治疗急性冠脉综合征(ACS)的临床疗效和安全性。方法:60例ACS患者随机分为治疗组和对照组。对照组给予阿司匹林单抗血小板治疗,治疗组采用阿司匹林+氯吡格雷双联抗血小板治疗,治疗3个月后评价临床疗效。结果:治疗组临床疗效总有效率为93.3%,显著高于对照组(76.7%),相比较有显著性差异(P<0.05);治疗后,两组LVEF、CO、E/A显著上升,与治疗前比较均有显著性差异(P<0.05);且治疗组与对照组比较有显著性差异(P<0.05)。结论:阿司匹林和氯吡格雷双联抗血小板药物治疗ACS,可以强化对血小板聚集的抑制,并增强抗栓效果,值得临床应用。     

双联抗血小板治疗急性冠脉综合征临床疗效观察

目的：探讨双联抗血小板治疗急性冠脉综合征（ACS）的临床疗效和安全性。方法：60例ACS患者随机分为治疗组和对照组。对照组给予阿司匹林单抗血小板治疗,治疗组采用阿司匹林＋氯吡格雷双联抗血小板治疗,治疗3个月后评价临床疗效。结果：治疗组临床疗效总有效率为93.3%,显著高于对照组（76.7%）,相比较有显著性差异（P〈0.05）;治疗后,两组LVEF、CO、E/A显著上升,与治疗前比较均有显著性差异（P〈0.05）;且治疗组与对照组比较有显著性差异（P〈0.05）。结论：阿司匹林和氯吡格雷双联抗血小板药物治疗ACS,可以强化对血小板聚集的抑制,并增强抗栓效果,值得临床应用。     

Serum biomarker discovery related to pathogenesis in acute coronary syndrome by proteomic approach

Acute coronary syndrome (ACS) results from inadequate supply of blood flow from the coronary arteries to the heart or ischemia. ACS has an extremely high morbidity and mortality. The levels of biomarkers currently used for detection of ACS also increase in response to myocardial necrosis and other diseases and are not elevated immediately after symptoms appear, thus limiting their diagnostic capacity. Therefore, we aimed to discover new ACS diagnostic biomarkers with high sensitivity and specificity that are specifically related to ACS pathogenesis. Sera from 50 patients with ACS and healthy controls (discovery cohort) each were analyzed using mass spectrometry (MS) to identify differentially expressed proteins, and protein candidates were evaluated as ACS biomarkers in 120 people in each group (validation cohort). α-1-acid glycoprotein 1 (AGP1), complement C5 (C5), leucine-rich α-2-glycoprotein (LRG), and vitronectin (VN) were identified as biomarkers whose levels increase and gelsolin (GSN) as a biomarker whose levels decrease in patients with ACS. We concluded that these biomarkers are associated with the pathogenesis of ACS and can predict the onset of ACS prior to the appearance of necrotic biomarkers.     

Metabolic pathways and physiological and pathological significances of lysolipid phosphate mediators

Lysophosphatidic acid and sphingosine 1-phosphate are structurally simple and physiologically very important lysophospholipids. Because they possess distinct structural backbones (glycerol and sphingosine, respectively), there are different metabolic pathways for their intracellular production. Recently, several key enzymes that produce or degrade these lysolipid phosphate mediators extracellularly have been characterized. This review focuses on the physiological and pathophysiological significances of the extracellular metabolic pathways involving recently characterized exo-type lysophospholipase D, ecto-type phospholipase A, and ecto-type lipid phosphate phosphatase.     

Revascularization in the acute coronary syndromes

Coronary heart disease is the leading cause of death worldwide, and occurs when the coronary arteries are unable to supply adequate oxygenated blood to the myocardium, which in turn can lead to ischemia and infarction of myocardial tissue. There are three options for revascularization in the setting of acute coronary syndromes. In select patients, coronary artery bypass surgery remains an option. Thrombolytics were initially the mainstay of therapy, which has now shifted to angioplasty, with or without stents, when readily available. Revascularization has been demonstrated to improve patient outcomes, and has evolved rapidly in the recent past.     

Role of aldehyde dehydrogenase 2 Glu504lys polymorphism in acute coronary syndrome

This study aimed to investigate the association of the aldehyde dehydrogenase 2 (ALDH2) Glu504Lys polymorphism, which exists in 30-50% of East Asians, and risk of acute coronary syndrome (ACS). We enrolled 1092 unrelated Han Chinese, including 546 with ACS and 546 age- and sex-matched controls. Subjects with ALDH2 mutant genotypes showed significantly higher ACS than did controls (46.7% versus 31.9%, P < 0.001). Logistic regression analysis revealed the ALDH2 mutant independently associated with ACS (odds ratio [OR] 1.95, 95% confidence interval [CI]: 1.31-2.92, P = 0.001), but the association was weaker on adjusting for alcohol consumption (OR 1.82, 95% CI: 1.23-2.70, P = 0.003). Similar results were found in a subgroup analysis of patients with primary ST-segment elevation myocardial infarction (STEMI). The ALDH2 mutant was significantly associated with level of high-sensitivity C-reactive protein (hs-CRP) in patients with ACS (P = 0.002) and in controls (P = 0.009) and number of circulating endothelial progenitor cells (EPCs) (P = 0.032); furthermore, inclusion of hs-CRP level and EPCs number as independent variables in regression analysis reduced the importance of ALDH2 polymorphism in ACS or primary STEMI. However, ALDH2 polymorphism was not associated with number of coronary arteries with significant stenosis, Gensini score or flow-mediated dilation of the brachial artery. Our results suggest that ALDH2 mutation is a genetic risk marker for ACS, which is explained in part by alcohol consumption, inflammation and number of circulating EPCs.     

Elevated homocysteine level and prognosis in patients with acute coronary syndrome: a meta-analysis

Objective: Controversial results exist with respect to the association between elevated homocysteine level and adverse prognosis in acute coronary syndrome (ACS) patients. We performed a meta-analysis to evaluate the prognostic value of homocysteine level on ACS patients.

Materials and methods: A comprehensive literature search of PubMed and Embase databases was conducted prior to August 2018. Prospective observational studies reporting the association of baseline homocysteine level with major adverse cardiovascular events (MACE), cardiovascular or all-cause mortality in ACS patients were selected. Pooled risk ratio (RR) and corresponding 95% confidence intervals (CI) were calculated for the highest versus the lowest homocysteine level.

Results: Ten studies including 4120 ACS patients were identified. ACS patients with the highest homocysteine level had an increased risk of MACE (RR 2.01; 95% CI 1.53–2.64) and all-cause mortality (RR 2.05; 95% CI 1.50–2.79) after controlling confounding factors. However, the association between elevated homocysteine level and cardiovascular mortality (RR 1.08; 95% CI 0.83–1.39) was not statistically significant.

Conclusions: Elevated homocysteine level was associated with an increased risk of MACE and all-cause mortality among ACS patients. However, the association of elevated homocysteine level with cardiovascular mortality in ACS patients should be further confirmed in future studies.     

Association between coronary endothelial dysfunction and local inflammation of atherosclerotic coronary arteries

We have examined a possibility whether or not severity and extent of coronary atherosclerosis may associate with degree of local inflammation in relation to endothelial dysfunction as is indicated by reduced NO formation. Blood samples were obtained from aortic root (Ao) and coronary sinus (CS) of 39 patients who underwent coronary angiography. Plasma NOx levels (nitrite + nitrate, stable NO end-products) were evaluated by HPLC-Griess system, and markers of inflammation, C-reactive protein (CRP) and serum amyloid A protein (SAA), were measured by Latex Turbidimetric Immunoassay. To evaluate the changes of these substances through coronary circulation, the percentage changes of respective markers [(CS – Ao) × 100/Ao] were calculated. The extent and severity of atherosclerosis of left coronary arteries were evaluated with Gensini Score (GS). The GS correlated with the percentage changes of NOx (r = –0.35, p < 0.05) and that of SAA (r = 0.43, p < 0.05) across coronary circulation, but not with changes in CRP. Moreover, the percentage changes of NOx correlated with that of SAA (r = –0.36, p < 0.05). These results indicated that severity and extent of coronary atherosclerosis related to degree of local inflammation which has a possible association with coronary endothelial dysfunction.     

Levels of zinc and lipid peroxidation in acute coronary syndrome

The present study was carried out on 20 female patients diagnosed with acute coronary syndrome (ACS). The control group was composed of 20 healthy female volunteers. Plasma malondialdehyde (MDA) levels and serum zinc (Zn), total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and VLDL-cholesterol, Lp(a), Apo-A₁, and Apo-B were determined in all patients and controls. Plasma MDA levels were determined to be significantly high in patients with ACS compared to the controls (1.75±0.27 vs 0.8±0.43 nmol/mL; p<0.05). On the other hand, Zn levels in patients with ACS were determined to be significantly low compared to the control group (67.9±14.8 vs 101.8±22.4 mg/dL; p<0.05). There was a statistically significant negative correlation between MDA and Zn levels in patients with ACS (r=−0.678, p<0.05). Other lipid parameters were significantly altered in patients with ACS compared to the controls (p<0.05). In conclusion, Zn and lipid peroxidation levels are important in patients with ACS and they must be monitored during diagnosis and treatment of these patients.     

Gender-specific differences in biomarkers responses to acute coronary syndromes and revascularization procedures

A growing body of gender-related research in coronary artery disease is beginning to gradually elucidate differences between women and men. In patients presenting with acute coronary syndromes (ACS), these sex differences include varying risk factor profiles, accuracy of diagnostic testing, clinical presentations, treatment practices and outcomes. There is also a differential expression of cardiac biomarkers by sex, which remains unexplained. This paper reviews all the available information on the effect of gender on cardiac biomarkers by search of MEDLINE using the terms gender differences, biomarkers, ACS and revascularization procedures. A better understanding of the sex disparities in biomarkers along with all other clinical information is essential to optimal management and patient care in the future.     

Aldehyde dehydrogenase 2 Glu504Lys variant predicts a worse prognosis of acute coronary syndrome patients

Aldehyde dehydrogenase 2 (ALDH2) Glu504Lys variant was an independent risk factor for acute coronary syndrome (ACS). However, there are lacking researches about the relationship between the variant and prognosis of ACS. In the prospective study, 377 ACS patients were grouped into the wild‐type (*1/*1) and the mutation (*2/*2 + *1/*2) groups according to genotype detection. Compared with the wild‐type group, incidences of major adverse cardiac events (MACE) and cardiac death were both higher in the mutation group (9.2% vs 21.0%, P = .002; 5.2% vs 12.2%, P = .026); the MACE‐free and the cardiac‐death‐free cumulative survival rates were obviously lower in the mutation group. Moreover, the mutant genotypes were associated with significantly increased risk of MACE and cardiac death (HR 2.443, 95%CI: 1.390‐4.296, P = .002; HR 2.727, 95%CI: 1.303‐5.708, P = .008). These results suggested that ALDH2 Glu504Lys variant could predict a worse prognosis of ACS patients.     

Paroxysmal atrial fibrillation triggered by a monomorphic ventricular couplet in a patient with acute coronary syndrome

Atrial fibrillation is a common arrhythmia in patients suffering from acute myocardial infarction, however its pathophysiological mechanisms are not fully understood. We describe the unusual case of a 76-year old woman admitted for non-ST-segment elevation myocardial infarction, who developed multiple episodes of paroxysmal atrial fibrillation triggered by monomorphic ventricular couplets. Beta-blocking and amiodarone therapy resulted efficacious in preventing arrhythmic recurrences. We then discuss the possible arrhythmogenic mechanisms, with special emphasis on the unique electrophysiological, hemodynamic, cellular and anatomical milieu created by acute myocardial ischemia.