Association of Matrix Metalloproteinase Levels with Collagen Degradation in the Context of Abdominal Aortic Aneurysm

Klaus, Veronika; Tanios-Schmies, F.; Reeps, Christian; Trenner, Matthias; Matevossian, Edouard; Eckstein, Hans‐Henning; Pelisek, Jaroslav

doi:10.1016/j.ejvs.2016.12.030

Cited by 37 publications

(25 citation statements)

References 36 publications

(25 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…32 However, the association between CKD and AAA remained significant even after accounting for these factors, in addition to a wide range of other potential confounders. Second, matrix metalloproteinases may mediate the CKD-AAA relationship since they play key roles in the pathogenesis of AAA, 33 as well as kidney fibrosis 34 and albuminuria. 35 Third, CKD induces systemic inflammation, a condition considered to increase the risk of AAA.…”

Section: Discussionmentioning

confidence: 99%

Chronic kidney disease measures and the risk of abdominal aortic aneurysm

et al. 2018

View full text Add to dashboard Cite

Background and aims: Despite its strong link to cardiovascular outcomes, the association of chronic kidney disease (CKD) with abdominal aortic aneurysm (AAA) has not been explicitly and comprehensively investigated. Methods: In 10,724 participants in the Atherosclerosis Risk in Communities Study (aged 53–75 years during 1996–1998), we evaluated the associations of two key CKD measures—estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (ACR) - with incident AAA (AAA diagnosis in outpatient, hospitalization discharge, or death records). Additionally, we performed a cross-sectional analysis for the CKD measures and ultrasound-based abdominal aortic diameter in 4,258 participants during 2011–2013. Results During a median follow-up of 13.9 years, 347 participants developed AAA. The demographically-adjusted hazard ratio (HR) was 4.44 (95% CI 1.58–12.49) for eGFR <30, 3.29 (1.89–5.72) for 30–44, 2.03 (1.29–3.19) for 45–59, and 1.62 (1.11–2.35) for 60–74 compared to eGFR ≥90 ml/min/1.73m2 and was 2.49 (1.28–4.87) for ACR ≥300, 1.99 (1.40–2.83) for 30–299, and 1.46 (1.08–1.97) for 10–29 compared to ACR <10 mg/g. The associations were generally similar after accounting for additional confounders, such as smoking (although attenuated), or after stratifying by subgroups, including diabetes. The cross-sectional analysis also showed continuous positive associations of these CKD measures with aortic diameter, particularly at the distal aortic segment assessed. Conclusions: Reduced eGFR and elevated albuminuria were independently associated with greater incidence of AAA and greater abdominal aortic diameter. Our results suggest the potential usefulness of CKD measures to identify persons at high risk of AAA and the need to investigate pathophysiological pathways linking CKD to AAA.

show abstract

Section: Discussionmentioning

confidence: 99%

Chronic kidney disease measures and the risk of abdominal aortic aneurysm

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Previous studies have reported a significant correlation between MMP-9 with coronary artery disease [ 20 ] and outcomes after acute myocardial infarction [ 21 ]. The overexpression of MMP-2, -8, -9, and -12 was related to abdominal aortic aneurysm [ 22 ]. Likewise, MMP-8, -9, and -12 seem to be associated with collagen I and collagen III, as well as their degradation products and vascular remodeling [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

Epigenetic hypomethylation and upregulation of matrix metalloproteinase 9 in Kawasaki disease

Kuo

Huang

et al. 2017

Oncotarget

View full text Add to dashboard Cite

BackgroundKawasaki disease (KD) is a type of febrile coronary vasculitis occurring in children. Some researchers have suggested that changes in genetic signatures, such as matrix metalloproteinases (MMPs), are critical markers for cardiovascular diseases. This study aims to provide a comprehensive survey of global DNA methylation levels and MMP transcripts of KD patients compared to control subjects.Materials and MethodsFor chips studies, we recruited a total of 18 KD patients, prior to receiving intravenous immunoglobulin (IVIG) and at least 3 weeks after IVIG treatment, as well as 18 healthy and 18 febrile control subjects. We applied Illumina HumanMethylation450 BeadChip and Affymetrix GeneChip® Human Transcriptome Array 2.0 to evaluate their CpG markers and expression levels, respectively. Then we used a separate cohort to carry out real-time quantitative PCR validations of mRNA levels.ResultsThe expressions of mRNA levels of MMP-8, -9, and -25 were significantly upregulated in KD patients compared to the healthy and febrile controls. Once KD patients underwent IVIG treatment, these MMPs considerably decreased. In particular, the methylation status of CpG sites of MMP-9 indicated a significant opposite tendency between both stages of not only the KD samples but also the controls. We also observed the mRNA level of MMP-9 to be higher in KD patients with coronary arterial lesion formation.ConclusionThis study is the first to report epigenetic hypomethylation, an increased MMP-9 transcript, and the upregulation of MMP-9 in KD patients who had formed coronary arterial lesions.

show abstract

“…For example, matrix metalloproteinase cleave col I while col III level increases 45 . Similarly, it was reported that TNF-alfa, a major pro-inflammatory cytokine, downregulates stromal alfa-SMA45 . Previously we demonstrated that p62 DNA quenches an ovariectomy-induced increase of TNF-alfa levels 29 .…”

mentioning

confidence: 76%

p62-DNA-encoding plasmid reverts tumor grade, changes tumor stroma, and enhances anticancer immunity

Venanzi

Gabai

Mariotti

et al. 2019

Preprint

View full text Add to dashboard Cite

Previously, we reported that the administration of a p62/SQSTM1-encoding plasmid demonstrates high safety and clinical benefits for human cancer patients, having also suppressed tumor growth and metastasis in dogs and mouse models. Here we investigated the mechanistic aspects of these effects. In mammary tumors bearing-dogs, p62 plasmid i.m. injections reduced tumor volumes, and reverted tumor grade to less aggressive lesions in 5 out of 6 animals, with one carcinoma switching to benign adenoma. The treatment increased levels of alpha-SMA in stroma cells and collagen 3 in the extracellular matrix, both of which correlate with a good clinical prognosis. p62 treatment also increased the abundance of intratumoral T-cell. To test the role of adaptive immunity, we compared protective effects of the plasmid against B16 melanoma in wild type C57BL/6J mice and in the corresponding SCID strain lacking lymphocytes. The plasmid was only protective in the wild type strain. Also, p62 plasmid amplified anti-tumor effect of adoptive T-cell transfer from tumor-bearing animals to animals challenged with the same tumors. We conclude that the plasmid acts indirectly via re-modeling of the tumor microenvironment, making it more favorable for increased anti-cancer immunity. Thus, the p62-encoding plasmid might be a new adjuvant for cancer treatments.

show abstract

Association of Matrix Metalloproteinase Levels with Collagen Degradation in the Context of Abdominal Aortic Aneurysm

Cited by 37 publications

References 36 publications

Chronic kidney disease measures and the risk of abdominal aortic aneurysm

Chronic kidney disease measures and the risk of abdominal aortic aneurysm

Epigenetic hypomethylation and upregulation of matrix metalloproteinase 9 in Kawasaki disease

p62-DNA-encoding plasmid reverts tumor grade, changes tumor stroma, and enhances anticancer immunity

Contact Info

Product

Resources

About