Identification of Mep1a as a susceptibility gene for atherosclerosis in mice

Genetics ◽  
2021 ◽  
Author(s):  
Andrew T Grainger ◽  
Nathanael Pilar ◽  
Jun Li ◽  
Mei-Hua Chen ◽  
Ashley M Abramson ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Bioinformatics Analysis ◽  
Susceptibility Gene ◽  
Arterial Disease ◽  
Chromosome 17 ◽  
Chow Diet ◽  
Atherosclerotic Lesions ◽  
Significant Locus ◽  
Atherosclerosis Development ◽  
Peripheral Arterial

Abstract 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 x 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 a 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.

scholarly journals Oxidative-stress-mediated arterial dysfunction in patients with peripheral arterial disease

2006 ◽  
Vol 28 (5) ◽  
pp. 608-612 ◽  
Author(s):  
L. Loffredo ◽  
A. Marcoccia ◽  
P. Pignatelli ◽  
P. Andreozzi ◽  
M.C. Borgia ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Peripheral Arterial Disease ◽  
Arterial Disease ◽  
Peripheral Arterial

Dynamic thiol/disulphide homeostasis metrics as a risk factor for peripheral arterial disease

Vascular ◽  
2020 ◽  
pp. 170853812094724
Author(s):  
Ufuk Turan Kursat Korkmaz ◽  
Ahmet Yuksel ◽  
Ayhan Cetinkaya ◽  
Yusuf Velioglu ◽  
Erhan Renan Ucaroglu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Risk Factor ◽  
Peripheral Arterial Disease ◽  
Laboratory Data ◽  
Arterial Disease ◽  
Control Group ◽  
Study Group ◽  
Total Thiol ◽  
Peripheral Arterial ◽  
Study Participants

Objective To examine dynamic thiol/disulphide homeostasis metrics as a novel risk factor of oxidative stress in patients with peripheral arterial disease. Methods One hundred patients with lower extremity peripheral arterial disease (a study group) and 100 control subjects were included in this prospective case–control study. Participants’ baseline clinical characteristics and laboratory data including some oxidant/antioxidant status parameters such as albumin, ferroxidase and myeloperoxidase, and thiol/disulphide homeostasis parameters such as native thiol, total thiol and disulphide, as well as native thiol/total thiol, disulphide/native thiol and disulphide/total thiol ratios were all recorded and then compared between the groups. Results Mean albumin and ferroxidase, and median myeloperoxidase levels were found to be significantly higher in patients with the peripheral arterial disease than in control group ( p = 0.045, p = 0.000 and p = 0.000, respectively). Mean native thiol and total thiol, and median disulphide levels were found to be significantly lower in the study group as compared with the control group ( p = 0.000, p = 0.000 and p = 0.037, respectively). According to the results of logistic regression analysis, systolic blood pressure, ferroxidase and myeloperoxidase levels were detected to be the independent predictors of peripheral arterial disease. Conclusion Our report is the first one in the literature investigating dynamic thiol/disulphide homeostasis metrics as a novel risk factor of oxidative stress in peripheral arterial disease. Dynamic thiol/disulphide homeostasis metrics may be used as a valuable risk factor of oxidative stress in patients with the peripheral arterial disease since it is readily available, easily calculated and relatively cheap.

scholarly journals Imbalance between nitric oxide generation and oxidative stress in patients with peripheral arterial disease: Effect of an antioxidant treatment

2006 ◽  
Vol 44 (3) ◽  
pp. 525-530 ◽  
Author(s):  
Lorenzo Loffredo ◽  
Pasquale Pignatelli ◽  
Roberto Cangemi ◽  
Paola Andreozzi ◽  
Maria Antonietta Panico ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Peripheral Arterial Disease ◽  
Arterial Disease ◽  
Antioxidant Treatment ◽  
Disease Effect ◽  
Peripheral Arterial ◽  
And Oxidative Stress

PO15-398 OXIDATIVE-STRESS MEDIATED ARTERIAL DYSFUNCTION IN PATIENTS WITH PERIPHERAL ARTERIAL DISEASE

2007 ◽  
Vol 8 (1) ◽  
pp. 115
Author(s):  
L. Loffredo ◽  
A. Marcoccia ◽  
P. Pignatelli ◽  
P. Andreozzi ◽  
L. Perri ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Peripheral Arterial Disease ◽  
Arterial Disease ◽  
Peripheral Arterial

scholarly journals Distal embolization during percutaneous revascularization of the lower extremity arteries

VASA ◽  
2020 ◽  
Vol 49 (5) ◽  
pp. 389-394
Author(s):  
Anja Boc ◽  
Aleš Blinc ◽  
Vinko Boc
Keyword(s):  
Vascular Diseases ◽  
Limb Ischemia ◽  
Arterial Disease ◽  
Antiplatelet Treatment ◽  
Distal Embolization ◽  
Atherosclerotic Lesions ◽  
Endovascular Revascularization ◽  
Chronic Critical Limb Ischemia ◽  
Percutaneous Revascularization ◽  
Peripheral Arterial

Summary: Background: Percutaneous endovascular therapy is nowadays the leading treatment option for patients with symptomatic peripheral arterial disease, but it can be complicated with distal embolization (DE). Patients and methods: We retrospectively analyzed 2054 endovascular revascularization interventions performed in patients with disabling claudication or chronic critical limb ischemia in the Catheterisation Laboratory of the Department of Vascular Diseases, University Medical Centre Ljubljana between January 2014 and December 2018. Lesions were treated by balloon angioplasty and/or stent implantation, without atherectomy. Results: The overall incidence of DE was 0.9%. DE was more frequent in females than males (1.6% vs 0.5%, p = 0.011), in the absence of antiplatelet treatment prior to intervention compared to previous antiplatelet treatment (2.1% vs 0.6%, p = 0.005) and in femoropopliteal stenting compared to angioplasty without stenting (2.2% vs 0.8%, p = 0.037). DE was successfully managed with percutaneous aspiration, in combination with angioplasty when necessary, in 84% of cases. In remaining 16% of patients, DE was managed with surgical thromboembolectomy. Conclusions: The incidence of DE during endovascular revascularization of chronic atherosclerotic lesions in lower limb arteries without use of atherectomy was low. DE was more frequent in women, in patients without prior antiplatelet treatment and in femoropopliteal stenting. The majority of DE was successfully managed percutaneously.

scholarly journals Skeletal Muscle Mitochondrial Dysfunction and Oxidative Stress in Peripheral Arterial Disease: A Unifying Mechanism and Therapeutic Target

Antioxidants ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 1304
Author(s):  
Kyoungrae Kim ◽  
Erik M. Anderson ◽  
Salvatore T. Scali ◽  
Terence E. Ryan
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Blood Flow ◽  
Mitochondrial Dysfunction ◽  
Strong Predictor ◽  
Clinical Pathology ◽  
Arterial Disease ◽  
Limb Amputation ◽  
Peripheral Arterial ◽  
And Oxidative Stress

Peripheral artery disease (PAD) is caused by atherosclerosis in the lower extremities, which leads to a spectrum of life-altering symptomatology, including claudication, ischemic rest pain, and gangrene requiring limb amputation. Current treatments for PAD are focused primarily on re-establishing blood flow to the ischemic tissue, implying that blood flow is the decisive factor that determines whether or not the tissue survives. Unfortunately, failure rates of endovascular and revascularization procedures remain unacceptably high and numerous cell- and gene-based vascular therapies have failed to demonstrate efficacy in clinical trials. The low success of vascular-focused therapies implies that non-vascular tissues, such as skeletal muscle and oxidative stress, may substantially contribute to PAD pathobiology. Clues toward the importance of skeletal muscle in PAD pathobiology stem from clinical observations that muscle function is a strong predictor of mortality. Mitochondrial impairments in muscle have been documented in PAD patients, although its potential role in clinical pathology is incompletely understood. In this review, we discuss the underlying mechanisms causing mitochondrial dysfunction in ischemic skeletal muscle, including causal evidence in rodent studies, and highlight emerging mitochondrial-targeted therapies that have potential to improve PAD outcomes. Particularly, we will analyze literature data on reactive oxygen species production and potential counteracting endogenous and exogenous antioxidants.

The Role of Combined Assessment of Defense Against Oxidative Stress and Inflammation in the Evaluation of Peripheral Arterial Disease

2011 ◽  
Vol 11 (6) ◽  
pp. 453-464 ◽  
Author(s):  
A. Rull ◽  
R. Garcia ◽  
L. Fernandez-Sender ◽  
R. Beltran-Debon ◽  
G. Aragones ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Peripheral Arterial Disease ◽  
Arterial Disease ◽  
Peripheral Arterial
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