Inflammation increases MMP levels via PGE2 in human vascular wall and plasma of obese women

Özen, Gülsev; Boumiza, Soumaya; Deschildre, Catherine; Topal, Gökçe; Longrois, Dan; Jakobsson, Per‐Johan; Michel, Jean‐Baptiste; Jacob, Marie‐Paule; Chahed, Karim; Norel, Xavier

doi:10.1038/s41366-018-0235-6

Cited by 17 publications

(12 citation statements)

References 71 publications

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“…Positive correlation observed between MMP-1 and CRP levels supported this hypothesis (Supplementary Table 2 ). Similar results were obtained 24 and discussed in our previous studies 22 , 24 . On the other hand, studies performed on relatively small numbers of participants (n = 54–102) showed that there is no difference in MMP-1 levels between obese and non-obese people 25 , 26 .…”

Section: Discussionsupporting

confidence: 92%

MMPs and TIMPs levels are correlated with anthropometric parameters, blood pressure, and endothelial function in obesity

Boumiza

Chahed

Tabka

et al. 2021

Sci Rep

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The association between matrix metalloproteinases (MMPs), tissue inhibitor of metalloproteinases (TIMPs) and obesity as well as obesity-related disease including metabolic syndrome is not fully explored. Our aims are that: (i) to evaluate the plasma levels of MMP-1, MMP-2, MMP-3, MMP-9, TIMP-1, TIMP-2 and their ratios in non-obese people, overweight and obese people with or without metabolic syndrome, (ii) to investigate correlations between MMPs or TIMPs levels and several anthropometric parameters, blood pressure, endothelial function. Anthropometric and biochemical parameters were determined in 479 randomly selected participants, subdividing according to body mass index (BMI) and metabolic syndrome status. Plasma MMPs and TIMPs levels were measured. The assessment of endothelial function was characterized in people with obesity, overweight and non-obese, using laser Doppler Flowmetry. Obese people have elevated MMP-1, MMP-2, TIMP-1, TIMP-2 levels and decreased MMP-3/TIMP-1 and MMP-9/TIMP-1 ratios compared with non-obese people. MMP-1 levels and MMP-1/TIMP-1 ratio were positively correlated with BMI and waist circumference (WC) while MMP-2 levels were negatively correlated with BMI and WC values in obese people. MMP-3 levels and MMP-3/TIMP-1 ratio were positively correlated with systolic blood pressure (SBP) or diastolic blood pressure (DBP) in obese and metabolic syndrome people. Additionally, MMP-9 levels and MMP-9/TIMP-1 ratio were negatively correlated with endothelium-dependent response in obese and metabolic syndrome people. MMP-1, MMP-2, TIMP-1, TIMP-2 levels were increased in obese subjects. Significant correlations between anthropometric parameters and MMP-1 as well as MMP-1/TIMP-1 ratio supported these results. MMP-3 and -9 levels as well as their ratios with TIMP-1 were associated with blood pressure and endothelial-dependent response, respectively. In conclusion, our results demonstrated that MMP-1, MMP-3 and MMP-9 levels were correlated with several obesity-related parameters including BMI, WC, blood pressure and endothelial-dependent response. Our findings will hopefully provide new aspects for the use of MMPs and TIMPs as clinical biomarkers in obesity-related cardiovascular diseases such as metabolic syndrome and hypertension. The lack of measure of MMPs activity in plasma and relevant organs/tissues in obesity and metabolic syndrome is considered as a limitation in this report.

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Section: Discussionsupporting

confidence: 92%

MMPs and TIMPs levels are correlated with anthropometric parameters, blood pressure, and endothelial function in obesity

Boumiza

Chahed

Tabka

et al. 2021

Sci Rep

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“…The infiltrating inflammatory cells and VSMCs could secrete various mediators including PGE 2 . PGE 2 increases the production of MMPs [30], which are suggested to play a prominent role in the degradation of the vascular wall as mentioned previously. Furthermore, the increased synthesis of PGE 2 in aneurysmal tissue may then recruit additional inflammatory cells and promote innate and adaptive immune responses, leading to continued aneurysmal degeneration.…”

supporting

confidence: 56%

Quercetin Downregulates Cyclooxygenase‐2 Expression and HIF‐1α/VEGF Signaling‐Related Angiogenesis in a Mouse Model of Abdominal Aortic Aneurysm

Lian

Xiong

et al. 2020

BioMed Research International

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Objective. Abdominal aortic aneurysm (AAA) development has been characterized by increased expression of vascular endothelial growth factor (VEGF), which contributes to angiogenesis via cyclooxygenase-2 (COX-2). Quercetin, one of the most common and well-researched flavonoids and abundant in vegetables and fruits, has beneficial effects in inhibiting angiogenesis. This study investigated the antiangiogenic effects of quercetin on experimental aneurysms. Methods. We utilized the in vivo AAA mouse model induced by the periaortic application of CaCl2 to examine the effectiveness of quercetin in blocking angiogenesis. Quercetin was administered at 60 mg/kg once daily on the day of the AAA induction and then continued for 6 weeks. Celecoxib, a selective COX-2 inhibitor, was used as the positive control. Results. Our results demonstrated that quercetin significantly attenuated aneurysm growth in AAA mice and medial neovascularization. Accordingly, quercetin decreased the expression of proangiogenic mediators, including VEGF-A, intercellular adhesion molecule-1, vascular cell adhesion molecule 1, and vascular endothelial cadherin. Quercetin treatment also inhibited the expression of COX-2 and hypoxia-inducible factor 1α (HIF-1α). It was also found that quercetin-3-glucuronide, a major quercetin metabolite, downregulated the expression of COX-2, HIF-1α, VEGF-A, and matrix metalloproteinase activities in aortic vascular smooth muscle cells isolated from AAA mice. Conclusion. Quercetin attenuates neovascularization during AAA growth, and this effect is mediated via the inhibition of COX-2, which decreases HIF-1α/VEGF signaling-related angiogenesis.

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“…Increased PGE-2 levels have been associated with several chronic diseases. For instance, PGE-2 was elevated in women with obesity [ 380 ], and especially in patients with cancer, including colorectal [ 381 ] and ovarian cancer [ 382 ]. Also T2D patients showed elevated concentrations [ 383 ], and its contribution to a variety of neurological disorders has been proposed [ 384 ].…”

Section: Markers Of Inflammation Relation To Disease and Practicamentioning

confidence: 99%

Common and Novel Markers for Measuring Inflammation and Oxidative Stress Ex Vivo in Research and Clinical Practice—Which to Use Regarding Disease Outcomes?

Menzel¹,

Samouda

Dohet³

et al. 2021

Antioxidants

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Many chronic conditions such as cancer, chronic obstructive pulmonary disease, type-2 diabetes, obesity, peripheral/coronary artery disease and auto-immune diseases are associated with low-grade inflammation. Closely related to inflammation is oxidative stress (OS), which can be either causal or secondary to inflammation. While a low level of OS is physiological, chronically increased OS is deleterious. Therefore, valid biomarkers of these signalling pathways may enable detection and following progression of OS/inflammation as well as to evaluate treatment efficacy. Such biomarkers should be stable and obtainable through non-invasive methods and their determination should be affordable and easy. The most frequently used inflammatory markers include acute-phase proteins, essentially CRP, serum amyloid A, fibrinogen and procalcitonin, and cytokines, predominantly TNFα, interleukins 1β, 6, 8, 10 and 12 and their receptors and IFNγ. Some cytokines appear to be disease-specific. Conversely, OS—being ubiquitous—and its biomarkers appear less disease or tissue-specific. These include lipid peroxidation products, e.g., F2-isoprostanes and malondialdehyde, DNA breakdown products (e.g., 8-OH-dG), protein adducts (e.g., carbonylated proteins), or antioxidant status. More novel markers include also –omics related ones, as well as non-invasive, questionnaire-based measures, such as the dietary inflammatory-index (DII), but their link to biological responses may be variable. Nevertheless, many of these markers have been clearly related to a number of diseases. However, their use in clinical practice is often limited, due to lacking analytical or clinical validation, or technical challenges. In this review, we strive to highlight frequently employed and useful markers of inflammation-related OS, including novel promising markers.

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Inflammation increases MMP levels via PGE2 in human vascular wall and plasma of obese women

Cited by 17 publications

References 71 publications

MMPs and TIMPs levels are correlated with anthropometric parameters, blood pressure, and endothelial function in obesity

MMPs and TIMPs levels are correlated with anthropometric parameters, blood pressure, and endothelial function in obesity

Quercetin Downregulates Cyclooxygenase‐2 Expression and HIF‐1α/VEGF Signaling‐Related Angiogenesis in a Mouse Model of Abdominal Aortic Aneurysm

Common and Novel Markers for Measuring Inflammation and Oxidative Stress Ex Vivo in Research and Clinical Practice—Which to Use Regarding Disease Outcomes?

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