Plasma <scp>MMP</scp> and <scp>TIMP</scp> evaluation in patients with deep venous thrombosis: could they have a predictive role in the development of post‐thrombotic syndrome?

Franciscis, Stefano de; Gallelli, Luca; Amato, Bruno; Butrico, Lucia; Rossi, Alessio; Buffone, Gianluca; Caliò, Francesco G.; Caridi, Giovanni De; Grande, Raffaele; Serra, Raffaele

doi:10.1111/iwj.12489

Cited by 33 publications

(48 citation statements)

References 48 publications

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“…De Franciscis et al (2015) demonstrated increased MMP-9 levels in the acute phase of DVT when compared to healthy controls. However, after a follow-up of 18 months, DVT patients presented similar MMP-9 levels to controls [45]. Our study evaluated patients with a mean time of 61 months after the last DVT episode and we found that DVT patients presented decreased MMP-9 levels when compared to no/mild PTS.…”

Section: Discussionmentioning

confidence: 48%

Increased inflammation and endothelial markers in patients with late severe post-thrombotic syndrome

Bittar¹,

Silva²,

Orsi³

et al. 2020

PLoS ONE

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IntroductionPost-thrombotic syndrome (PTS) is a limiting long-term complication present in 20-50% of patients with deep venous thrombosis (DVT) of the lower limbs. A panel of biomarkers with potential relevance to enhance knowledge on the pathophysiology of PTS was investigated. MethodsThis case-control study included 93 patients with DVT in the lower limbs, 31 with severe PTS (cases) and 62 with mild/no PTS (controls), over 24 months after an acute episode. Thirty-one healthy individuals (HI) with no history of DVT were included as a reference to the population. FVIII activity, D-dimer, inflammatory cytokines, endothelial dysfunction markers, matrix metalloproteinases, and their inhibitors, tissue remodeling and growth factor levels were evaluated. The classification of PTS was, by the Villalta scale. ResultsPatients with severe PTS showed elevated levels of CRP, sICAM-1, sE-selectin, and decreased MMP-9 and MCP-1 levels when compared to patients with mild/no PTS. Moreover, DVT patients presented higher levels of FVIII and D-dimer when compared to HI. ConclusionsDVT patients present an inflammatory status, endothelial dysfunction and altered proteolysis MMPs activity, even a long time after the acute thrombotic episode, which is more significant in severe PTS. These results suggest a possible role of these mediators in the maintenance and worsening of PTS severity.

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Section: Discussionmentioning

confidence: 48%

Increased inflammation and endothelial markers in patients with late severe post-thrombotic syndrome

Bittar¹,

Silva²,

Orsi³

et al. 2020

PLoS ONE

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“…Various MMPs patterns have been identified to indicate several stages within the disease. MMP‐2, MMP‐9 and NGAL (which is a protein belonging to the lipocalin family, with the ability to positively modulate the activities of MMP‐9) appear to be mostly involved in the acute phase of vascular disease (such as aneurysm rupture and pulmonary embolism) , while MMP‐1 and MMP‐8 appear to be primarily involved with chronic or irreversible complications of vascular disease (such as difficult‐to‐heal or infected venous ulcers and post‐thrombotic syndrome) .…”

Section: Discussionmentioning

confidence: 99%

“…MMPs are a group of several multi-domain zinc-dependent enzymes that are involved in the remodelling of several components of ECM (24). In the vasculature, MMPs influence the migration, proliferation and apoptosis of vascular smooth muscle cells, endothelial cells and inflammatory cells, thereby affecting intima formation, atherosclerosis, aneurysms, varicose veins and its complications, such as venous ulceration and post-thrombotic syndrome (6)(7)(8)(9)(10)(11)(12)(13)(14)25,26). Various MMPs patterns have been identified to indicate several stages within the disease.…”

Section: Discussionmentioning

confidence: 99%

“…Various MMPs patterns have been identified to indicate several stages within the disease. MMP-2, MMP-9 and NGAL (which is a protein belonging to the lipocalin family, with the ability to positively modulate the activities of MMP-9) appear to be mostly involved in the acute phase of vascular disease (such as aneurysm rupture and pulmonary embolism) (27,28), while MMP-1 and MMP-8 appear to be primarily involved with chronic or irreversible complications of vascular disease (such as difficult-to-heal or infected venous ulcers and post-thrombotic syndrome) (13,14,26). The ADAMs are a family of transmembrane and secreted proteins that have functions in cell adhesion and the proteolytic processing of the ectodomains of diverse cell surface receptors and signalling molecules, and they have been identified in many species.…”

Section: Discussionmentioning

confidence: 99%

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From varices to venous ulceration: the story of chronic venous disease described by metalloproteinases

Serra

Gallelli²,

Butrico

et al. 2016

International Wound Journal

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Chronic venous disease (CVD) and its most frightening complication, chronic venous ulceration (CVU), represent an important socioeconomic burden in the western world. Metalloproteinases have been identified in the pathogenesis of several vascular diseases such as venous problems. The aim of this study was to evaluate a broad range of metalloproteinases, such as matrix metalloproteinases (MMPs), ADAMs (a disintegrin and metalloproteinases) and ADAMTSs (a disintegrin and metalloproteinases with thrombospondin motifs) and their inhibitors, tissue inhibitor of metalloproteinases (TIMPs) and a related protein, neutrophil gelatinase-associated lipocalin (NGAL), in patients with CVD in order to correlate their serum levels with each stage of the disease. We performed a multicenter open-label study that comprised the enrolment of 541 patients with CVD of clinical stages C1-C6, (178 males, 363 females; mean age 57·29, median age 53·72, age range 29-81); 29 subjects without CVD were included in this study (9 males and 20 females; mean age 54·44, median age 50, age range 28-84) as the control group. Enzyme-linked immunosorbent assay (ELISA) was performed for measuring serum levels of proteases and related proteins. The study found that the serum elevation of MMP-2, ADAMTS-1 and ADAMTS-7 appeared to be correlated with the initial stages of CVD, whereas the serum elevation of MMP-1, MMP-8, MMP-9, NGAL, ADAM-10, ADAM-17 and ADAMTS-4 was particularly involved in skin change complications. This study showed that each stage of CVD may be described by particular patterns of metalloproteinases, and this may have therapeutic implications in discovering new targets and new drugs for the treatment of CVD.

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“…In a recent cohort study, patients with PTS showed higher levels of MMP‐1 and MMP‐8 during the acute phase of DVT compared to patients without PTS . MMP‐1 and MMP‐8 may be markers of fibrosis during the inflammatory process, and further studies are indicated to determine their role as potential biomarkers for PTS.…”

Section: Risk Factorsmentioning

confidence: 99%

The postthrombotic syndrome: current evidence and future challenges

Rabinovich

Kahn

2017

Journal of Thrombosis and Haemostasis

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Postthrombotic syndrome (PTS) is a chronic complication of deep vein thrombosis (DVT) that develops in 20-50% of patients. PTS manifests as a spectrum of symptoms and signs of chronic venous insufficiency that can impose significant morbidity and have a negative impact on quality of life. Chronic venous hypertension caused by a combination of residual venous obstruction and valvular reflux is believed to play a major role in the pathophysiology of PTS. The Villalta scale is the most widely applied clinical scale used to diagnose and define PTS. Proximal DVT and recurrent ipsilateral DVT are the two principal established risk factors for PTS, and efforts in recent years have been focused on identifying a combination of clinical and biomarker predictors that will define high-risk patients and possibly new therapeutic targets. The best way to prevent PTS is to prevent the occurrence of DVT, and to provide optimal anticoagulation for the acute phase of DVT once it occurs. Recent years have brought progress in our understanding of the role of endovascular techniques in the prevention and treatment of PTS and the subgroups of patients that may benefit from these modalities. Pharmacomechanical catheter-directed thrombolysis is the most promising interventional modality for prevention of PTS. This review summarizes the current state of evidence on PTS of the lower limbs, and highlights areas where uncertainty still exists that require further research.

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Plasma MMP and TIMP evaluation in patients with deep venous thrombosis: could they have a predictive role in the development of post‐thrombotic syndrome?

Cited by 33 publications

References 48 publications

Increased inflammation and endothelial markers in patients with late severe post-thrombotic syndrome

Increased inflammation and endothelial markers in patients with late severe post-thrombotic syndrome

From varices to venous ulceration: the story of chronic venous disease described by metalloproteinases

The postthrombotic syndrome: current evidence and future challenges

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