Lectine Pathway in Unstable Carotid Plaque
Study Details
Study Description
Brief Summary
The study is aimed to investigate the possible role of lectin pathway - an alternative pathway of complement activation - in affecting stability of carotid atherosclerotic plaques and the possible correlations with clinical neurologic features.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Detailed Description
In addition to the known hemodynamic criteria, instable carotid plaques can be responsible for brain ischemia, therefore is paramount to identify preoperatively possible markers of plaque instability. The study is aimed to investigate the possible role of lectin pathway - an alternative pathway of complement activation - in affecting stability of carotid atherosclerotic plaques and the possible correlations with clinical neurologic features. Study population will include 40 patients with internal carotid artery stenosis >=70% (assessed by echocolordoppler), symptomatic or asymptomatic, surgically treated by endoarterectomy. Removed plaques will be evaluated by histologic exam and immunofluorescence for ficolins 1-2-3 and Mannose Binding Lectin (MBL). Plasma samples will be used for ELISA test of lectin pathway complement activation.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| asymptomatic asymptomatic patients undergoing carotid endoarterectomy for stenosis >70% (velocimetric criteria at echodoppler) |
Procedure: Carotid endoarterectomy
Surgical removal of carotid bifurcation plaque and arterial repair (direct suture or patch)
Other Names:
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| symptomatic symptomatic (TIA, crescendo TIA, minor stroke) patients undergoing carotid endoarterectomy, independently from stenosis evaluated by echodoppler |
Procedure: Carotid endoarterectomy
Surgical removal of carotid bifurcation plaque and arterial repair (direct suture or patch)
Other Names:
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Outcome Measures
Primary Outcome Measures
- lectine pathway of complement activation in carotid plaques [preoperative]
assessment of association between plasmatic levels of complement activators and plaque instability (histologic index). Protein plasma levels will be assessed as optical density. Plaque instability will be quantified by a vulnerability score that combines four different histological parameters according to their quartile distribution (Fumagalli et al., Frontiers Immunology 2017). Their association will be analyzed as odds ratio (95%-CI) by a Fisher test.
Secondary Outcome Measures
- focal neurologic symptoms and plasmatic levels of complement activators [preoperative, postoperative day 3, 3 months after surgery]
Correlation of onset of focal neurologic symptoms (TIA, any stroke) due to carotid stenosis and peripheral plasma levels of complement activators. Neurological exam + CT or MNR will be used as clinical measurement tool
- focal neurologic symptoms and histologic index of plaque instability [through study completion (average 1 year)]
correlation of onset of focal neurologic symptoms (TIA, any stroke) due to carotid stenosis and histologic index for plaque instability. Protein plasma levels will be assessed as optical density. Plaque instability will be quantified by a vulnerability score that combines four different histological parameters according to their quartile distribution (Fumagalli et al., Frontiers Immunology 2017).
Eligibility Criteria
Criteria
Inclusion Criteria:
- patients undergone elective or urgent carotid endoarterectomy (CEA) for internal carotid stenosis >70% (assessed by velocimetric criteria) with or without neurologic symptoms
Exclusion Criteria:
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recent (<20 days) major/minor stroke with positive CT scan
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absolute contraindications to surgery (cardiac, respiratory, anesthesiologic risk)
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Investigators
- Principal Investigator: Angela MR Ferrante, MD, Fondazione Policlinico Universitario A.Gemelli IRCCS Roma
Study Documents (Full-Text)
None provided.More Information
Publications
- Füst G, Munthe-Fog L, Illes Z, Széplaki G, Molnar T, Pusch G, Hirschberg K, Szegedi R, Széplaki Z, Prohászka Z, Skjoedt MO, Garred P. Low ficolin-3 levels in early follow-up serum samples are associated with the severity and unfavorable outcome of acute ischemic stroke. J Neuroinflammation. 2011 Dec 29;8:185. doi: 10.1186/1742-2094-8-185.
- Hellings WE, Pasterkamp G, Vollebregt A, Seldenrijk CA, De Vries JP, Velema E, De Kleijn DP, Moll FL. Intraobserver and interobserver variability and spatial differences in histologic examination of carotid endarterectomy specimens. J Vasc Surg. 2007 Dec;46(6):1147-54. Epub 2007 Oct 22.
- Longhi L, Orsini F, De Blasio D, Fumagalli S, Ortolano F, Locatelli M, Stocchetti N, De Simoni MG. Mannose-binding lectin is expressed after clinical and experimental traumatic brain injury and its deletion is protective. Crit Care Med. 2014 Aug;42(8):1910-8. doi: 10.1097/CCM.0000000000000399.
- Osthoff M, Katan M, Fluri F, Schuetz P, Bingisser R, Kappos L, Steck AJ, Engelter ST, Mueller B, Christ-Crain M, Trendelenburg M. Mannose-binding lectin deficiency is associated with smaller infarction size and favorable outcome in ischemic stroke patients. PLoS One. 2011;6(6):e21338. doi: 10.1371/journal.pone.0021338. Epub 2011 Jun 21.
- Pilely K, Fumagalli S, Rosbjerg A, Genster N, Skjoedt MO, Perego C, Ferrante AMR, De Simoni MG, Garred P. C-Reactive Protein Binds to Cholesterol Crystals and Co-Localizes with the Terminal Complement Complex in Human Atherosclerotic Plaques. Front Immunol. 2017 Aug 29;8:1040. doi: 10.3389/fimmu.2017.01040. eCollection 2017.
- Verhoeven B, Hellings WE, Moll FL, de Vries JP, de Kleijn DP, de Bruin P, Busser E, Schoneveld AH, Pasterkamp G. Carotid atherosclerotic plaques in patients with transient ischemic attacks and stroke have unstable characteristics compared with plaques in asymptomatic and amaurosis fugax patients. J Vasc Surg. 2005 Dec;42(6):1075-81.
- Zangari R, Zanier ER, Torgano G, Bersano A, Beretta S, Beghi E, Casolla B, Checcarelli N, Lanfranconi S, Maino A, Mandelli C, Micieli G, Orzi F, Picetti E, Silvestrini M, Stocchetti N, Zecca B, Garred P, De Simoni MG; LEPAS group. Early ficolin-1 is a sensitive prognostic marker for functional outcome in ischemic stroke. J Neuroinflammation. 2016 Jan 20;13:16. doi: 10.1186/s12974-016-0481-2.
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