Plasma levels and zymographic activities of matrix metalloproteinases 2 and 9 in type II diabetics with peripheral arterial disease

Signorelli, Salvatore Santo; Malaponte, Grazia; Libra, Massimo; Pino, Luigi Di; Celotta, Gabriella; Bevelacqua, Valentina; Petrina, Marcello; Nicotra, Giulio Cesare; Indelicato, Manuela; Navolanic, Patrick M.; Pennisi, Giuseppe; Mazzarino, María Clorinda

doi:10.1191/1358863x05vm582oa

Cited by 107 publications

(90 citation statements)

References 36 publications

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“…Thus, we hypothesize that N is useful in identifying the activated process of macrophage cells in patients with chronic PAD. It is known that different biomarkers of inflammation, such as interleukins or metalloproteinases are elevated both in chronic and more severe PAD patients (32)(33)(34)(35)(36)(37)(38). Results of this study have shown the involvement of activated macrophages in chronic arterial disease of the lower limbs, albeit not symptomatic.…”

Section: Discussionmentioning

confidence: 55%

Neopterin: A potential marker in chronic peripheral arterial disease

Signorelli

Anzaldi

Fiore

et al. 2013

Molecular Medicine Reports

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Abstract. Neopterin is a marker of macrophage activation that has exhibited high plasma levels in atherosclerotic diseases including coronary heart disease and critical limb ischemia. The role of neopterin in chronic peripheral arterial disease (PAD) has yet to be elucidated. In the present study, neopterin (Ν) serum concentrations were analyzed in asymptomatic (AsP) and symptomatic (SyP) patients with PAD as well as controls (C). In total 120 subjects, 40 AsP [ankle brachial index (ABI) ≤0.90], 40 SyP (ABI ≤0.90 plus pain in legs) and 40 controls (ABI >0.9) were enrolled. The results of the present study showed that neopterin plasma levels were statistically different among the groups. These findings demonstrated that activation of N-mediated monocyte-macrophage, was also observed in chronic PAD.

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Section: Discussionmentioning

confidence: 55%

Neopterin: A potential marker in chronic peripheral arterial disease

Signorelli

Anzaldi

Fiore

et al. 2013

Molecular Medicine Reports

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“…Increased circulating concentrations of MMP-2 have been observed in pediatric patients with type 1 diabetes who developed microangiopathy over a 5-year interval (9). Systemic concentrations of MMP-2 and MMP-9, in addition to gelatinase activity levels, are also increased in patients with type 2 diabetes and peripheral arterial disease (10).…”

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confidence: 85%

Matrix Metalloproteinase-2 Dysregulation in Type 1 Diabetes

et al. 2007

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OBJECTIVE -Dysregulation of matrix metalloproteinase (MMP)-2 may contribute pathologically to the development of diabetes complications, including diabetic retinopathy and coronary and peripheral arterial disease. Our objective was to explore whether systemic MMP-2 dysregulation could be demonstrated in type 1 diabetes and to determine how MMP-2 concentration relates to disease status.RESEARCH DESIGN AND METHODS -In this cross-sectional study, MMP-2 concentrations and MMP-2 activity were measured in plasma and timed urine samples from 93 type 1 diabetic and 50 healthy control subjects, aged 14 -40 years. Relationships between MMP-2 concentrations in these biological fluids and subject characteristics (sex, age, and duration of type 1 diabetes), indexes of glycemic control (A1C, fasting plasma glucose, and continuous glucose monitoring system average daily glucose), and measurements of renal function (urinary albumin excretion and glomerular filtration rate) were examined.RESULTS -Urine and plasma MMP-2 concentrations and plasma MMP-2 activity were all significantly elevated in type 1 diabetic subjects compared with those in control subjects. Urine MMP-2 concentrations, in particular, were correlated with several clinical parameters that infer increased risk for diabetic comorbidity and specifically for diabetic nephropathy, including higher A1C, longer duration of disease, evidence of renal hyperfiltration, and the presence of microalbuminuria.CONCLUSIONS -Urine and plasma MMP-2 concentrations are dysregulated in type 1 diabetes; urinary excretion of MMP-2, in particular, might provide a unique biomarker of diabetes-induced intrarenal pathologic processes. Diabetes Care 30:2321-2326, 2007M atrix metalloproteinases (MMPs) constitute a group of enzymes that hydrolyze protein components of the extracellular matrix (1). The subgroup of MMPs known as gelatinases, specifically gelatinase A (MMP-2) and gelatinase B (MMP-9) digest collagen, denatured collagens (i.e., gelatins), laminin, elastin, and fibronectin, among other substrates (2), and have been implicated in the pathological processes that contribute to fibrotic diseases, tumor progression, and inflammation (1,3,4).Dysregulation of gelatinase activity has also been implicated in the pathophysiology of diabetes complications. Specifically, gelatinase concentrations are increased in the systemic circulation ) and in the vitreous (MMP-2 [6] and MMP-9 [7]) of type 1 diabetic patients with diabetic retinopathy. Elevated retinal levels of MMP-2 and MMP-9 have also been demonstrated in an animal model of diabetic retinopathy (8). Increased circulating concentrations of MMP-2 have been observed in pediatric patients with type 1 diabetes who developed microangiopathy over a 5-year interval (9). Systemic concentrations of MMP-2 and MMP-9, in addition to gelatinase activity levels, are also increased in patients with type 2 diabetes and peripheral arterial disease (10).Data suggesting a link between MMP-2 dysregulation and diabetic nephropathy also exist but appear contra...

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“…Excessive activation of MMP-2 and MMP-9 combined with persistent nitrosative and oxidative stress and with excessive formation of advanced glycation end-products leads to ECM instability and to the breakdown of essential matrix proteins and growth factors [102][103][104][105]. Diabetic individuals show delayed reepithelialisation [106] and altered sensitivity to VEGF resulting in decreased angiogenesis [107].…”

Section: Pathologies/comorbiditiesmentioning

confidence: 99%

Impaired wound healing: facts and hypotheses for multi-professional considerations in predictive, preventive and personalised medicine

Avishai¹,

2017

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Whereas the physiologic wound healing (WH) successfully proceeds through the clearly defined sequence of the individual phases of wound healing, chronic non-healing wounds/ulcers fail to complete the individual stages and the entire healing process. There are many risk factors both modifiable (such as stress, smoking, inappropriate alcohol consumption, malnutrition, obesity, diabetes, cardio-vascular disease, etc.) and non-modifiable (such as genetic diseases and ageing) strongly contributing to the impaired WH. Current statistics demonstrate that both categories are increasingly presented in the populations, which causes dramatic socio-economic burden to the healthcare sector and society at large. Consequently, innovative concepts by predictive, preventive and personalised medicine are crucial to be implemented in the area. Individual risk factors, causality, functional interrelationships, molecular signature, predictive diagnosis, and primary and secondary prevention are thoroughly analysed followed by the expert recommendations in this paper.

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Plasma levels and zymographic activities of matrix metalloproteinases 2 and 9 in type II diabetics with peripheral arterial disease

Cited by 107 publications

References 36 publications

Neopterin: A potential marker in chronic peripheral arterial disease

Neopterin: A potential marker in chronic peripheral arterial disease

Matrix Metalloproteinase-2 Dysregulation in Type 1 Diabetes

Impaired wound healing: facts and hypotheses for multi-professional considerations in predictive, preventive and personalised medicine

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