Altered Metalloproteinase-9 Expression as Least Common Denominator between Varicocele, Inguinal Hernia, and Chronic Venous Disorders

Serra, Raffaele; Buffone, Gianluca; Costanzo, Giuseppe; Montemurro, Rossella; Scarcello, Edoardo; Stillitano, Domenico M; Damiano, Rocco; Franciscis, Stefano de

doi:10.1016/j.avsg.2013.07.026

Cited by 42 publications

(58 citation statements)

References 18 publications

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“…In the present study, we have documented that MMP-2, MMP-8, MMP-9, and NGAL were strongly expressed in patients with mixed wound etiology with respect to the control Group C. Recently, several authors reported the involvement of MMPs in venous ulcers26,49,50 and their association with NGAL values 20,51. In the present study, we documented higher levels of NGAL in patients with mixed ulcer that could justify the severity of mixed vascular pathology observed in our study group.…”

Section: Discussionsupporting

confidence: 68%

“…As previously described,8,15,19–26 the pathophysiological processes that characterize chronic ulcer onset are the activation of immune system cells and the secretion of specific protease enzymes known as MMPs. Previously, we documented that MMPs are involved in several vascular diseases 48…”

Section: Discussionmentioning

confidence: 96%

“…In order to evaluate plasma MMPs and NGAL levels, blood samples were collected at the time of the admission in accordance with our previous studies 20–26…”

Section: Methodsmentioning

confidence: 99%

“…Immunoblotting was performed using anti-MMP-2, MMP-8, MMP-9, and anti-NGAL monoclonal antibodies (monoclonal antibody kit against activated form of MMPs; Millipore Corporation) that recognized only activated MMPs and NGAL, and results have been expressed as arbitrary units, as recently described 20–26. All experiments were performed in triplicate.…”

Section: Methodsmentioning

confidence: 99%

“…Several studies have shown that MMPs play a central role in the pathophysiology of venous and arterial diseases15–26 and in related diseases 27. Neutrophil gelatinase-associated lipocalin (NGAL) is a protein belonging to the lipocalin family and is expressed by activated neutrophils.…”

Section: Introductionmentioning

confidence: 99%

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The effects of sulodexide on both clinical and molecular parameters in patients with mixed arterial and venous ulcers of lower limbs

Serra¹,

Gallelli²,

A³

et al. 2014

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BackgroundMixed venous and arterial ulcers account for approximately 15%–30% of all venous leg ulcerations. Several studies have shown that matrix metalloproteinases (MMPs) and neutrophil gelatinase-associated lipocalin (NGAL) play a central role in the pathophysiology of venous and arterial diseases. Some studies have shown the efficacy of glycosaminoglycans, such as sulodexide (SDX), in treating patients with leg ulcers. The aim of this study was to evaluate clinical effects of SDX and its correlation with MMPs and NGAL expression in patients with mixed arterial and venous leg ulcers.MethodsPatients eligible for this study were of both sexes, older than 20 years, and with a clinical and instrumental diagnosis of mixed ulcer.ResultsFifty-three patients of both sexes were enrolled and divided into two groups by means of randomization tables. Group A (treated group) comprised 18 females and ten males (median age: 68.7 years) treated with standard treatment (compression therapy and surgery) + SDX (600 lipoprotein lipase-releasing units/day intramuscularly) for 15 days followed by SDX 250 lipase-releasing units every 12 hours day orally for 6 months as adjunctive treatment. Group B (control group) comprised 17 females and eight males (median age: 64.2 years) treated with standard treatment only (compression therapy and surgery). The type of surgery was chosen according to anatomical level of vein incompetence: superficial venous open surgery and/or subfascial endoscopic perforating surgery. In all enrolled patients, blood samples were collected in order to evaluate the plasma levels of MMPs and NGAL through enzyme-linked immunosorbent assay. These results were compared to another control group (Group C) of healthy individuals. Moreover, biopsies of ulcers were taken to evaluate the tissue expression of MMPs and NGAL through Western blot analysis. Our results revealed that SDX treatment is able to reduce both plasma levels and tissue expression of MMPs improving the clinical conditions in patients with mixed ulcers.ConclusionInhibition of MMPs could represent a possible therapeutic intervention to limit the progression of leg ulceration. In particular, our findings demonstrate the efficacy of SDX in patients with mixed arterial and venous chronic ulcers of the lower limbs.

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Section: Discussionsupporting

confidence: 68%

Section: Discussionmentioning

confidence: 96%

“…In order to evaluate plasma MMPs and NGAL levels, blood samples were collected at the time of the admission in accordance with our previous studies 20–26…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%