Atherosclerosis is the underlying cause of heart attack, ischemic stroke and peripheral arterial disease, and genetic factors involved remain mostly unidentified. We previously identified a significant locus on mouse chromosome 17 for atherosclerosis, Ath49, in an intercross between BALB/c and SM strains. Ath49 partially overlaps in the confidence interval with Ath22 mapped in an AKR × DBA/2 intercross. Bioinformatics analysis prioritized Mep1a, encoding meprin 1α metalloendopeptidase, as a likely candidate gene for Ath49. To prove causality, Mep1a-/-Apoe-/- mice were generated and compared with Mep1a+/+Apoe-/- mice for atherosclerosis development. Mep1a was found abundantly expressed in atherosclerotic lesions but not in healthy aorta and liver of mice. Mep1a-/- Apoe-/- mice exhibited significant reductions in both early and advanced lesion sizes. Loss of Mep1a led to decreased necrosis but increased macrophage and neutrophil contents in advanced lesions, reduced plasma levels of CXCL5 and an oxidative stress biomarker. In addition, Mep1a-/- mice had significantly reduced triglyceride levels on a chow diet. Thus, Mep1a is a susceptibility gene for atherosclerosis and aggravates atherosclerosis partially through action on oxidative stress and inflammation.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8664597 | PMC |
| http://dx.doi.org/10.1093/genetics/iyab160 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
An inflammation-related gene landscape predicts prognosis and response to immunotherapy in virus-associated hepatocellular carcinoma.
Front Oncol
March 2023
Department of Biochemistry and Molecular Biology, School of Bioscience and Technology, Chengdu Medical College, Chengdu, Sichuan, China.
Background: Due to the viral infection, chronic inflammation significantly increases the likelihood of hepatocellular carcinoma (HCC) development. Nevertheless, an inflammation-based signature aimed to predict the prognosis and therapeutic effect in virus-related HCC has rarely been established.
Method: Based on the integrated analysis, inflammation-associated genes (IRGs) were systematically assessed.
Identification of Mep1a as a susceptibility gene for atherosclerosis in mice.
Genetics
December 2021
Departments of Biochemistry & Molecular Genetics, University of Virginia, Charlottesville, VA 22908, USA.
Atherosclerosis is the underlying cause of heart attack, ischemic stroke and peripheral arterial disease, and genetic factors involved remain mostly unidentified. We previously identified a significant locus on mouse chromosome 17 for atherosclerosis, Ath49, in an intercross between BALB/c and SM strains. Ath49 partially overlaps in the confidence interval with Ath22 mapped in an AKR × DBA/2 intercross.
View Article and Find Full Text PDFGenetic analysis of atherosclerosis identifies a major susceptibility locus in the major histocompatibility complex of mice.
Atherosclerosis
November 2016
Department of Biochemistry & Molecular Genetics, University of Virginia, Charlottesville, VA, USA; Department of Radiology and Medical Imaging, University of Virginia, Charlottesville, VA, USA. Electronic address:
Background And Aims: Recent genome-wide association studies (GWAS) have identified over 50 significant loci containing common variants associated with coronary artery disease. However, these variants explain only 26% of the genetic heritability of the disease, suggesting that many more variants remain to be discovered. Here, we examined the genetic basis underlying the marked difference between SM/J-Apoe and BALB/cJ-Apoe mice in atherosclerotic lesion formation.
View Article and Find Full Text PDFendoProteoFASP: a novel FASP approach to profile salivary peptidome and disclose salivary proteases.
Talanta
January 2015
QOPNA, Mass spectrometry center, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal. Electronic address:
The salivary peptidome, which can represent up to 20% of total secreted proteins in human saliva, is highly influenced by proteolytic events. However, the development of strategies to understand the dynamics underlying the generation of salivary peptides has been a challenging task. In order to disclose in more detail the proteolytic events taking place in saliva, we aimed to characterize salivary peptidome and predict salivary proteases by applying, for the first time, a filter-aided sample preparation (FASP) approach to saliva.
View Article and Find Full Text PDFAssociation of MEP1A gene variants with insulin metabolism in central European women with polycystic ovary syndrome.
Gene
March 2014
Division of Endocrinology and Metabolism, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, A-8036 Graz, Austria.
Polycystic ovary syndrome (PCOS) shows not only hyperandrogenemia, hirsutism and fertility problems, but also metabolic disturbances including obesity, cardiovascular events and type-2 diabetes. Accumulating evidence suggests some degree of inflammation associated with prominent aspects of PCOS. We aimed to investigate the association of genetic variants 3'UTR rs17468190 (G/T) of the inflammation-associated gene MEP1A (GenBank ID: NM_005588.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!