Urokinase-generated plasmin activates matrix metalloproteinases during aneurysm formation

Carmeliet, Peter; Moons, Lieve; Lijnen, Roger; Baes, Myriam; Lemaı̂tre, V.; Tipping, Peter G.; Drew, Angela F.; Eeckhout, Yves; Shapiro, Steve D.; Lupu, Florea; Collen, D.

doi:10.1038/ng1297-439

Cited by 613 publications

(517 citation statements)

References 25 publications

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“…Several studies -much more than cited at the end of this sentence -have speculated that serine proteases, particularly plasmin, are in vivo activators of proMMPs, including some of the furinactivated MMPs (Carmeliet et al, 1997;Creemers et al, 2000;Monea et al, 2002;Okumura et al, 1997;Ramos-DeSimone et al, 1999). In fact, the concept that plasmin functions to activate latent MMPs is oft accepted as dogma (Janssens and Lijnen, 2006;Lo et al, 2003), however, the data in support of this mechanism is mostly circumstantial.…”

Section: Activation Of Prommps By Plasmin and Other Serine Proteinasesmentioning

confidence: 99%

Control of matrix metalloproteinase catalytic activity

2007

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SummaryAs their name implies, MMPs were first described as proteases that degrade extracellular matrix proteins, such as collagens, elastin, proteoglycans, and laminins. However, studies of MMP function in vivo have revealed that these proteinases act on a variety of extracellular protein substrates, often to activate latent forms of effector proteins, such as antimicrobial peptides and cytokines, or to alter protein function, such as shedding of cell-surface proteins. Because their substrates are diverse, MMPs are involved in variety of homeostatic functions, such as bone remodeling, wound healing, and several aspects of immunity. However, MMPs are also involved in a number of pathological processes, such as tumor progression, fibrosis, chronic inflammation, tissue destruction, and more. A key step in regulating MMP proteolysis is the conversion of the zymogen into an active proteinase. Several proMMPs are activated in the secretion pathway by furin proprotein convertases, but for most the activation mechanisms are largely not known. In this review, we discuss both authentic and potential mechanisms of proMMP activation.

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Section: Activation Of Prommps By Plasmin and Other Serine Proteinasesmentioning

confidence: 99%

Control of matrix metalloproteinase catalytic activity

2007

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“…Plasminogen/plasmin system enzymes interact with the MMPs (Cuzner et al, 1996;Cuzner and Opdenakker, 1999). Serine proteases and urokinase-type and tissue-type plasminogen activators (uPA and tPA, respectively) participate in the activation of the MMPs (Mazzieri et al, 1997;Carmeliet et al, 1997). They are involved in normal extracellular remodeling and angiogenesis and in the pathological processes associated with tumor growth (Mignatti and Rifkin, 1996).…”

Section: Induction and Activation Of The Mmpsmentioning

confidence: 99%

Matrix metalloproteinases in neuroinflammation

Rosenberg

2002

Glia

781

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Matrix metalloproteinases (MMPs) are a gene family of neutral proteases that are important in normal development, wound healing, and a wide variety of pathological processes, including the spread of metastatic cancer cells, arthritic destruction of joints, atherosclerosis, and neuroinflammation. In the central nervous system (CNS), MMPs have been shown to degrade components of the basal lamina, leading to disruption of the blood-brain barrier (BBB), and to contribute to the neuroinflammatory response in many neurological diseases. Brain cells express both constitutive and inducible MMPs in response to cellular stress. MMPs are tightly regulated to avoid unwanted proteolysis. Secreted as inactive enzymes, the MMPs require activation by other proteases and free radicals. The MMPs are part of a larger class of metalloproteinases (MPs), which includes the recently discovered ADAMs (a disintegrin and metalloproteinase domain) and ADAMTS (a disintegrin and metalloproteinase thrombospondin) families. MPs have complex roles at the cell surface and within the extracellular matrix. At the cell surface, they act as sheddases, releasing growth factors, death receptors, and death-inducing ligands, making them important in cell survival and death. Tissue inhibitors of metalloproteinases (TIMPs) are endogenous inhibitors that regulate the activity of the MMPs. Synthetic inhibitors have been developed for the treatment of arthritis and cancer. These hydroxymate-based compounds have been shown to reduce injury in experimental allergic encephalomyelitis (EAE), experimental allergic neuritis (EAN), cerebral ischemia, intracerebral hemorrhage, and viral and bacterial infections. MPs have both beneficial and detrimental roles; understanding their expression in various CNS insults will allow for the use of MMP inhibitors in the treatment of neurological disorders. GLIA 39: 279 -291, 2002.

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“…9 MMPs are secreted as inactive preenzymes and are transformed into active forms after cleavage of a propeptide domain of the molecule. 10 In particular, MMP-2 and MMP-9, which are capable of degrading Type IV collagen (the major component of the basement membrane), are involved in the spread of various carcinomas. Tissue inhibitors of metalloproteinase (TIMPs) are the major endogenous regulators of MMPs and consist of four homologous members.…”

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confidence: 99%

Characteristics of primary care physicians and their practices associated with mammography rates for older women

Harrison

Janz

Wolfe

et al. 2003

Cancer

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BACKGROUND Mammography screening rates are below national recommendations for older women. Understanding the relation between the characteristics of primary care physicians (PCPs) and mammography rates for older women can help to target screening improvement efforts. METHODS Subjects were 2527 PCPs practicing in Michigan between 1997 and 1998. A cross‐sectional design used Medicare data to identify women age 68 years or older in 1998 whom PCPs treated in 1997–1998 and to determine whether these women had a mammogram between 1996 and1998. Eligible women were Medicare beneficiaries age 65 years or older by 1996, residing in Michigan from 1996 to 1998, without specified comorbidities likely to affect decisions regarding mammography. Correlations and multiple regressions examined the relation between this score and characteristics of both PCPs and their practice populations of older women. RESULTS Mammography rates across physicians' practices ranged from 3–100% (mean = 59%, standard deviation = 17%). Five predictors accounted for 55% of the variance in mammography rates across practices. Higher mammography rates were found to be independently related to physicians who have: a lower mean age for female Medicare patients, a higher mean number of physicians billing for patients' care, a lower mean number of inpatient admissions, obstetrics/gynecology practices, and a higher mean education level in patient's zip code (beta weights ≥ 0.25, P < 0.0001). CONCLUSIONS PCPs vary substantially with regard to mammography rates for older women. Mammography rates vary more with the population of patients in physicians' practices than with commonly measured personal characteristics of physicians. Mammography rates should be adjusted for patient population to target individual PCPs with low mammography rates for interventions. Cancer 2003. © 2003 American Cancer Society.

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Urokinase-generated plasmin activates matrix metalloproteinases during aneurysm formation

Cited by 613 publications

References 25 publications

Control of matrix metalloproteinase catalytic activity

Control of matrix metalloproteinase catalytic activity

Matrix metalloproteinases in neuroinflammation

Characteristics of primary care physicians and their practices associated with mammography rates for older women

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