Recent progress in phospholipase A₂ research: from cells to animals to humans.

Cardiovascular disease (CVD) is the leading cause of death and disability worldwide. The primary prevention of CVD is dependent upon the ability to identify high-risk individuals long before the development of overt events. This highlights the need for accurate risk stratification. An increasing number of novel biomarkers have been identified to predict cardiovascular events. Biomarkers play a critical role in the definition, prognostication, and decision-making regarding the management of cardiovascular events. This review focuses on a variety of promising biomarkers that provide diagnostic and prognostic information. The myocardial tissue-specific biomarker cardiac troponin, high-sensitivity assays for cardiac troponin, and heart-type fatty acid binding proteinall help diagnose myocardial infarction (MI) in the early hours following symptoms. Inflammatory markers such as growth differentiation factor-15, high-sensitivity C-reactive protein, fibrinogen, and uric acid predict MI and death. Pregnancy-associated plasma protein A, myeloperoxidase, and matrix metalloproteinases predict the risk of acute coronary syndrome. Lipoprotein-associated phospholipase A2 and secretory phospholipase A2 predict incident and recurrent cardiovascular events. Finally, elevated natriuretic peptides, ST2, endothelin-1, mid-regional-pro-adrenomedullin, copeptin, and galectin-3 have all been well validated to predict death and heart failure following a MI and provide risk stratification information for heart failure. Rapidly developing new areas, such as assessment of micro-RNA, are also explored. All the biomarkers reflect different aspects of the development of atherosclerosis.

Novel biomarkers for cardiovascular risk prediction.

Phospholipases A2 (PLA2s) belong to a superfamily of enzymes that catalyze the hydrolysis of glycerophospholipids at the sn-2 position, producing nonesterified fatty acids, such as arachidonic acid, and lysophospholipids.1,2 In many cases, the PLA2 lipid products lead to the generation of a variety of downstream signaling molecules, including prostaglandins, leukotrienes, lysophospholipids, platelet-activating factor (PAF), and oxidized lipids, that induce a multitude of biological actions in virtually all tissues, including the cardiovascular system.3,–,8 PLA2s comprise distinct sets of enzymes with different localizations: 1 cytosolic enzymes that are Ca2+-dependent (cPLA2), Ca2+-independent (iPLA2), or specific for PAF (intracellular PAF-acetylhydrolase); and 2 extracellular enzymes, either associated with lipoproteins (Lp-PLA2, also known as the secreted PAF acetylhydrolase) or typically secreted (sPLA2) and present in the extracellular space. The cPLA2 family consists of 6 enzymes, among which the cytosolic Ca2+-dependent cPLA2α (85 kDa, group IVA) plays a major role in the initiation of arachidonic acid metabolism from cell membrane phospholipids.9 The iPLA2 or patatin-like phospholipase domain–containing (PNPLA) family contains 9 enzymes, some of which work as phospholipases and others as lipases, with the Ca2+-independent iPLA2-β (88 to 90 kDa, group VIA-2) being one of the best-studied members.8,10 Lp-PLA2 exhibits unique substrate specificity toward PAF and oxidized phospholipids (oxPLs).11 The sPLA2 family consists of 10 isozymes with low molecular mass that are involved in a number of biological processes, including eicosanoid generation, inflammation, and host defense against bacterial infection.12

Arterial inflammation plays a central role in the pathogenesis of atherosclerosis and adverse cardiovascular events. Although cPLA2-α and iPLA2-β are likely to contribute …

Lipoprotein-Associated and Secreted Phospholipases A2 in Cardiovascular Disease

Phospholipids are present in all living organisms. They are a major component of all biological membranes, along with glycolipids and cholesterol. Enzymes aimed at cleaving the various bonds in phospholipids, namely phospholipases, are consequently widespread in nature, playing very diverse roles from aggression in snake venom to signal transduction, lipid mediators production, and digestion in humans. Although all phospholipases target phospholipids as substrates, they vary in the site of action on the phospholipids molecules, physiological function, mode of action, and their regulation. Significant studies on phospholipases characterization, physiological role, and industrial potential have been conducted worldwide. Some of them have been directed for biotechnological advances, such as gene discovery and functional enhancement by protein engineering. Others reported phospholipases as virulence factors and major causes of pathophysiological effects. In this introductory chapter, we provide brief details of different phospholipases.

https://faculty.washington.edu/gelb/documents/10.1007_978-1-61779-600-5_4.pdf

Phospholipases: An Overview

Hepatic secretion of apolipoprotein-B (apoB), the major protein of atherogenic lipoproteins, is regulated through posttranslational degradation. We reported a degradation pathway, post-ER pre secretory proteolysis (PERPP), that is increased by reactive oxygen species (ROS) generated within hepatocytes from dietary polyunsaturated fatty acids (PUFA). We now report the molecular processes by which PUFA-derived ROS regulate PERPP of apoB. ApoB exits the ER; undergoes limited oxidant-dependent aggregation; and then, upon exit from the Golgi, becomes extensively oxidized and converted into large aggregates. The aggregates slowly degrade by an autophagic process. None of the oxidized, aggregated material leaves cells, thereby preventing export of apoB-lipoproteins containing potentially toxic lipid peroxides. In summary, apoB secretory control via PERPP/autophagosomes is likely a key component of normal and pathologic regulation of plasma apoB levels, as well as a means for remarkably late-stage quality control of a secreted protein.

https://www.pnas.org/content/pnas/105/15/5862.full.pdf

Presecretory oxidation, aggregation, and autophagic destruction of apoprotein-B: A pathway for late-stage quality control

Objective— To study the distribution of group V secretory phospholipase A2 (sPLA2) in human and mouse lesions and compare its expression by human vascular cells, its activity toward lipoproteins, and the interaction with arterial proteoglycans (proteoglycans) with those of sPLA2-IIA. In addition, we also investigated the effect of a Western diet and lipopolysaccharide challenge on the aortic expression of these enzymes in mouse models.

Methods and Results— Immunohistochemistry showed sPLA2-V in human and mouse lesions to be associated with smooth muscle cells and also surrounding foam cells in lipid core areas. mRNA of the enzyme was expressed in human lesions and human vascular cells, supporting the immunohistochemistry data. sPLA2-V but not sPLA2-IIA was active on lipoproteins in human serum. The association with proteoglycans enhanced 2- to 3-fold sPLA2-V activity toward low-density lipoproteins but not that of the group IIA enzyme. Experiments in mouse models showed that treatment with a Western diet induced expression of sPLA2-V but not that of sPLA2-IIA in aorta. On the other hand, lipopolysaccharide-induced acute inflammation augmented the expression of sPLA2-IIA but not that of sPLA2-V.

Conclusions— These results indicate that these phospholipases could have different roles in atherosclerosis.

Secretory phospholipase A2 group V: lesion distribution, activation by arterial proteoglycans, and induction in aorta by a Western diet.

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

Philippe Cronet

Author Tools

Chat about Author

Papers

Secretory phospholipase A2 group V: lesion distribution, activation by arterial proteoglycans, and induction in aorta by a Western diet.