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Case control study of patients with and without restenosis to demonstrate the link between in-stent restenosis and an excessive skin healing. Patients will undergo skin biopsy and blood sample tests to search for a relationship between both processes and for the identification of biomarkers and therapeutic targets.
Restenosis represents an excessive response to the coronary stent. On the other hand, skin healing with keloid formation is also an excessive repair response. There is evidence that both processes may be related because they share mechanisms mediated by inflammatory response. The purpose is to demonstrate the correlation between them for the identification of biomarkers and therapeutic targets.
The project is a case-control study with 2 groups of patients: a control group of 40 patients with ≥1 bare metal stent which in a posterior catheterization performed by clinical follow-up had no restenosis and a group of 20 patients with ≥1 bare metal stent and 20 patients with ≥1 drug eluting stent which had restenosis in a posterior catheterization also performed by clinical follow-up.
A skin biopsy will be performed at the baseline visit from which primary cell cultures of fibroblasts and keratinocytes will be obtained. Four to six weeks later a second biopsy on the scar will be performed and analyzed anatomically and pathologically. In addition, at the initial visit, blood samples will be drawn for analysis of inflammation markers, RNA and proteins. Studies can be performed at 3 levels:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group of controls | Control group of 40 patients with ≥1 bare metal stent which in a posterior catheterization performed by clinical follow-up had no restenosis |
| |
| Group of cases | Group of cases with 20 patients with ≥1 bare metal stent and 20 patients with ≥1 drug eluting stent which had restenosis in a posterior catheterization performed by clinical follow-up. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Skin biopsy and blood sample for inflammation markers, RNA and proteins | Diagnostic Test | A skin biopsy will be performed at the baseline visit from which primary cell cultures of fibroblasts and keratinocytes will be obtained. Four to six weeks later a second biopsy on the scar will be performed and analyzed anatomically and pathologically. In addition, at the initial visit, blood samples will be drawn for analysis of inflammation markers, RNA and proteins. |
| Measure | Description | Time Frame |
|---|---|---|
| Link between in-stent restenosis and excessive skin healing | Percentage of patients in case and control groups with hypertrophic pattern of skin healing after the first biopsy | Through study completion, an average of 1 year |
| Measure | Description | Time Frame |
|---|---|---|
| Response of skin cells to antiproliferative drugs | Comparison of the proliferation rate of primary skin fibroblasts, from patients of the different groups, undergoing treatment with an antiproliferative drug. The continuous variable will be the percentage of living cells at the end of the treatment with respect to the initial cells, and mean values in the groups will be statistically compared. | Through study completion, an average of 1 year |
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Inclusion Criteria:
Exclusion Criteria:
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Patients with bare metal stents without restenosis will be included in the group of controls and those with restenosis will be included in the group of cases, 20 with bare metal and 20 with drug eluting stents).
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| Name | Affiliation | Role |
|---|---|---|
| Iñigo Lozano, MD, PHD | Hospital Cabuenes | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of Cardiology, Hospital Cabueñes | Gijón | Principality of Asturias | 33203 | Spain |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 9697822 | Result | Komatsu R, Ueda M, Naruko T, Kojima A, Becker AE. Neointimal tissue response at sites of coronary stenting in humans: macroscopic, histological, and immunohistochemical analyses. Circulation. 1998 Jul 21;98(3):224-33. doi: 10.1161/01.cir.98.3.224. | |
| 18042333 | Result | Ozdol C, Turhan S, Tulunay C, Altin AT, Atmaca Y, Candemir B, Erol C. Association between proliferative scars and in-stent restenosis. J Cutan Med Surg. 2007 Nov-Dec;11(6):206-10. doi: 10.2310/7750.2007.00039. |
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| ID | Term |
|---|---|
| D023903 | Coronary Restenosis |
| D002921 | Cicatrix |
| D007627 | Keloid |
| ID | Term |
|---|---|
| D023921 | Coronary Stenosis |
| D003327 | Coronary Disease |
| D017202 | Myocardial Ischemia |
| D006331 | Heart Diseases |
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| ID | Term |
|---|---|
| D001800 | Blood Specimen Collection |
| ID | Term |
|---|---|
| D013048 | Specimen Handling |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
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Two skin biopsies of the shoulder and blood samples
|
| Circulating microRNA profile | Determination of the profile and levels of circulating microRNAs in patients from the different groups. Plasma samples from some individuals in each group will be analyzed using a microarray. To assess the level of circulating microRNAs in all patients, real-time reverse transcription-polymerase chain reaction will be used. Mean values in the groups will be statistically compared. | Through study completion, an average of 1 year |
| Blood levels of immune cell subsets related to vascular repair and endothelial damage, including antiogenic T-cells, immunosenescent T-cells, monocyte subsets and low-density granulocytes. | These populations will be measured in samples of peripheral blood or isolated mononuclear cells by flow cytometry according to the expression of their surface markers | Through study completion, an average of 1 year |
| 9426044 | Result | Kornowski R, Hong MK, Tio FO, Bramwell O, Wu H, Leon MB. In-stent restenosis: contributions of inflammatory responses and arterial injury to neointimal hyperplasia. J Am Coll Cardiol. 1998 Jan;31(1):224-30. doi: 10.1016/s0735-1097(97)00450-6. |
| 20378849 | Result | Albinsson S, Suarez Y, Skoura A, Offermanns S, Miano JM, Sessa WC. MicroRNAs are necessary for vascular smooth muscle growth, differentiation, and function. Arterioscler Thromb Vasc Biol. 2010 Jun;30(6):1118-26. doi: 10.1161/ATVBAHA.109.200873. Epub 2010 Apr 8. |
| 17478730 | Result | Ji R, Cheng Y, Yue J, Yang J, Liu X, Chen H, Dean DB, Zhang C. MicroRNA expression signature and antisense-mediated depletion reveal an essential role of MicroRNA in vascular neointimal lesion formation. Circ Res. 2007 Jun 8;100(11):1579-88. doi: 10.1161/CIRCRESAHA.106.141986. Epub 2007 May 3. |
| 26429127 | Result | Sato T, Iwasaki Y, Kikkawa Y, Fukagawa M. An efficacy of intensive vitamin D delivery to neointimal hyperplasia in recurrent vascular access stenosis. J Vasc Access. 2016 Jan-Feb;17(1):72-7. doi: 10.5301/jva.5000469. Epub 2015 Sep 30. |
| 17261663 | Result | Inoue T, Sata M, Hikichi Y, Sohma R, Fukuda D, Uchida T, Shimizu M, Komoda H, Node K. Mobilization of CD34-positive bone marrow-derived cells after coronary stent implantation: impact on restenosis. Circulation. 2007 Feb 6;115(5):553-61. doi: 10.1161/CIRCULATIONAHA.106.621714. Epub 2007 Jan 29. |
| 17909106 | Result | Hur J, Yang HM, Yoon CH, Lee CS, Park KW, Kim JH, Kim TY, Kim JY, Kang HJ, Chae IH, Oh BH, Park YB, Kim HS. Identification of a novel role of T cells in postnatal vasculogenesis: characterization of endothelial progenitor cell colonies. Circulation. 2007 Oct 9;116(15):1671-82. doi: 10.1161/CIRCULATIONAHA.107.694778. Epub 2007 Oct 1. |
| 23548835 | Result | Rodrigues-Diez R, Lavoz C, Carvajal G, Rayego-Mateos S, Rodrigues Diez RR, Ortiz A, Egido J, Mezzano S, Ruiz-Ortega M. Gremlin is a downstream profibrotic mediator of transforming growth factor-beta in cultured renal cells. Nephron Exp Nephrol. 2012;122(1-2):62-74. doi: 10.1159/000346575. Epub 2013 Mar 14. |
| 18086474 | Result | Maciel TT, Melo RS, Schor N, Campos AH. Gremlin promotes vascular smooth muscle cell proliferation and migration. J Mol Cell Cardiol. 2008 Feb;44(2):370-9. doi: 10.1016/j.yjmcc.2007.10.021. Epub 2007 Nov 12. |
| 23053782 | Result | Ravelli C, Mitola S, Corsini M, Presta M. Involvement of alphavbeta3 integrin in gremlin-induced angiogenesis. Angiogenesis. 2013 Jan;16(1):235-43. doi: 10.1007/s10456-012-9309-6. Epub 2012 Sep 30. |
| 37325628 | Derived | Lozano I, Bangueses R, Rodriguez I, Pevida M, Rodriguez-Aguilar R, Rodriguez D, Espasandin-Arias M, Llames S, Meana A, Suarez A, Rodriguez-Carrio J. In-stent restenosis is associated with proliferative skin healing and specific immune and endothelial cell profiles: results from the RACHEL trial. Front Immunol. 2023 May 31;14:1138247. doi: 10.3389/fimmu.2023.1138247. eCollection 2023. |
| D002318 |
| Cardiovascular Diseases |
| D014652 | Vascular Diseases |
| D005355 | Fibrosis |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D003095 | Collagen Diseases |
| D003240 | Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D011677 | Punctures |
| D013514 | Surgical Procedures, Operative |
| D008919 | Investigative Techniques |