Matrix metalloproteinases and their tissue inhibitors in hypertension-related pregnancy complications

Karthikeyan, Vellore J; Lane, Deirdre A.; Beevers, D. G.; Lip, Gregory Y.H.; Blann, Andrew D.

doi:10.1038/jhh.2012.8

Cited by 35 publications

(30 citation statements)

References 103 publications

(51 reference statements)

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“…15 The matrix metalloproteinase (MMP) system has been a suggested mechanism for the remodeling of systemic arteries during pregnancy. 16 Circulating MMP-9 levels are higher in normal pregnancy as compared non-pregnant women. 17 In women with pregnancy induced hypertension, MMP-9 levels are raised, but the circulating levels of tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) are also raised.…”

Section: Discussionmentioning

confidence: 98%

Association of Parity With Carotid Diameter and Distensibility

et al. 2014

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Pregnancy and childbirth are associated with hemodynamic changes and vascular remodeling. It is not known whether parity is associated with later adverse vascular properties such as larger arterial diameter, wall thickness and lower distensibility. We used baseline data from 3283 women free of cardiovascular disease aged 45-84 years enrolled in the population based Multi-Ethnic Study of Atherosclerosis. Participants self-reported parity status. Ultrasound derived carotid artery lumen diameters and brachial artery blood pressures were measured at peak-systole and end-diastole. Common carotid intima media thickness (cIMT) was also measured. Regression models to determine the association of carotid distensibility coefficient, lumen diameter, and cIMT with parity were adjusted for age, race, height, weight, diabetes, current smoking, BP medication use, total and high density lipoprotein cholesterol levels. The prevalence of nulliparity was 18%. In adjusted models, carotid distensibility coefficient was 0.09 × 10−5Pa−1 lower (p = 0.009) in parous vs. nulliparous women. Among parous women, there was a nonlinear association with the greatest carotid DC seen in women with 2 live births, and significantly lower distensibility seen in primiparas (p=0.04) or with higher parity > 2 (p=0.005). No such pattern of association with parity was found for lumen diameter or cIMT. Parity is associated with lower carotid artery distensibility, suggesting arterial remodeling that lasts beyond childbirth. These long-term effects on the vasculature may explain the association of parity with cardiovascular events later in life.

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Section: Discussionmentioning

confidence: 98%

Association of Parity With Carotid Diameter and Distensibility

et al. 2014

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“…However, very few of these regulatory factors have been investigated in depth. Recent reports have demonstrated that MMP-9 down-regulation and TIMP-1 up-regulation can both lead to reduced trophoblast invasiveness [15,16,17]. We have also investigated the roles of MMP-9 and TIMP-1 in trophoblast invasion.…”

Section: Discussionmentioning

confidence: 99%

“…MMP-9 and TIMP-1 are both closely associated with trophoblast invasion. Down-regulation of MMP-9 and up-regulation of TIMP-1 may both lead to decreased trophoblast invasion [16,17,18]. …”

Section: Introductionmentioning

confidence: 99%

CDX2 Enhances HTR-8/SVneo Trophoblast Cell Invasion by Altering the Expression of Matrix Metalloproteinases

Jia

Ding²,

Gu³

et al. 2014

Cell Physiol Biochem

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Background/Aims: The invasion of trophoblast cells into the maternal uterine decidua is critical for normal placentation, establishment of pregnancy and maintenance of fetal growth in humans. Several growth factors and cytokines have been implicated in trophoblast invasion, but the underlying regulatory mechanisms of invasion are not fully understood. Our earlier studies have found that caudal-related homeobox transcription factor 2 (CDX2) is hypomethylated in human pre-eclampsia placental tissues. However, whether CDX2 is involved in trophoblast invasion was unclear. Methods and Results: In this study, we investigated CDX2 function using a human HTR-8/SVneo cell line that overexpressed CDX2. Cell invasion assays demonstrated that CDX2 enhanced trophoblast cell invasiveness. Meanwhile, MTT assays revealed that CDX2 did not affect cell proliferation. Western blot analysis and quantitative real-time PCR demonstrated that the expression level of matrix metalloproteinase-9 (MMP-9) was significantly increased, whereas the expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) was markedly suppressed in the CDX2-overexpressing trophoblast cells. The phosphoinositide-3-kinase (PI3K)/Akt signaling pathway is involved in proliferation, migration, metastasis and invasion. Our study showed that inhibition of PI3K/Akt signaling led to decreased expression of CDX2. Conclusion: We concluded that CDX2 is likely regulated by the PI3K/Akt signaling pathway during trophoblast cell invasion. Our findings may reveal new insights into the regulatory mechanisms of trophoblast cell invasion and may be an important contributor to the pathogenesis of pregnancy-related diseases.

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“…They often bind with heparin sulphate glycosaminoglycans on the cell surface and have wide range of substrates [11]. …”

Section: Reviewmentioning

confidence: 99%

Matrix metalloproteinases in autism spectrum disorders

Abdallah

Michel

2013

J Mol Psychiatry

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Autism Spectrum Disorders (ASD) are group of developmental disabilities with a complex neurobiological basis including putative changes in the immune system. They are characterized by pervasive qualitative abnormalities in social interactions, communication, and stereotyped behaviour. Matrix metalloproteinases (MMPs) represent a group of proteases which play an important role in neuroinflammation and neurodevelopment. Therefore, they possibly have a crucial function in the etiopathology of ASD. In this review, we summarize the plausibility of the hypothesis that MMPs are involved in the neuropathology of ASD. Possible pathways through which MMPs can contribute to the pathogenesis of ASD are discussed including neuroinflammatory mechanisms inclusive of mediating neuropathological effects of infections, the associations between MMPs and other biomarkers such as cytokines, chemokines and neurotrophic factors. Despite sufficient evidence for such an involvement of MMPs in the neuropathology of ASD, they have not yet been extensively studied in this context. Thus, further research in this field is not only urgently needed but also very promising and may also lead to new therapeutic approaches.

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Matrix metalloproteinases and their tissue inhibitors in hypertension-related pregnancy complications

Cited by 35 publications

References 103 publications

Association of Parity With Carotid Diameter and Distensibility

Association of Parity With Carotid Diameter and Distensibility

CDX2 Enhances HTR-8/SVneo Trophoblast Cell Invasion by Altering the Expression of Matrix Metalloproteinases

Matrix metalloproteinases in autism spectrum disorders

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