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Effects of rosuvastatin on the acute inflammatory response mediators IL-1, IL-6, IL-8, TNF-±, TGF-², MCP-1/CCL-2, PAI-1, C-reactive protein and nitric oxide after implantation of nonpharmacologic coronary stent

Grant number: 12/22989-1
Support type:Regular Research Grants
Duration: April 01, 2013 - March 31, 2015
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Alexandre Antônio Cunha Abizaid
Grantee:Alexandre Antônio Cunha Abizaid
Home Institution: Instituto Dante Pazzanese de Cardiologia (IDPC). Fundação Adib Jatene (FAJ). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
Assoc. researchers: Juliano Rasquin Slhessarenko ; Mario Hiroyuki Hirata ; Paula Helena Ortiz Lima

Abstract

Restenosis has limited long-term efficacy and success of percutaneous angioplasty with use of microproteses (stents) in coronary atherosclerotic lesions. Preliminary studies have shown that after the initial injury with catheter balloon or coronary stents, there is endothelial denudation, dissection, platelet deposition and leukocyte attraction as an immediate response, leading to long-term restenosis. A predominant histologic response fibrocellular at sites of previous angioplasty restenosis was also demonstrated. Three phases are described in the restenosis process: an inflammatory, cell proliferation and one of a graininess remodeling involving the synthesis of extracellular matrix. Endothelial dysfunction may persist for three months after vascular injury, being more pronounced after stenting non-pharmacological. After angioplasty, occurs leukocyte recruitment and infiltration of the vessel wall, initiating the inflammatory process, which can lead to proliferation of smooth muscle cells and accordingly intimal hyperplasia. Potentially, this place in the vessel injury after stenting can promote gene expression and release of inflammatory mediators, interleukins, acute phase proteins and clotting factors, platelet deposition and thrombus formation. These processes can be directly related to the prognosis of cardiovascular disease, but there are few studies that characterize the acute inflammatory response after stenting non-pharmacological as well as correlating the genetic analysis and the release of these mediators to angioplasty and restenosis. In this sense, the use of drug-eluting stents with anti-inflammatory drugs and vasodilators delays and / or reduces inflammation and intimal hyperplasia, possessing anti-proliferative properties. However, in Brazil, due to costs, the use of non-pharmacological stent is routinely over the use of drug-eluting stents, it is crucial to investigate the inflammatory reaction after implantation of coronary stents. Therefore, detection of the levels of inflammatory mediators as well as the understanding of the mechanisms involved cytogenetic prenatal and immediately after coronary stenting and the use of drugs with anti-inflammatory pharmacological properties, such as rosuvastatin oral pre-procedure could help in predicting adverse events such as thrombosis and restenosis and improve patient outcomes. Not available in the literature of studies analyzing the effects of rosuvastatin in the acute phase after coronary stenting. This study aims to assess the effects of rosuvastatin on the acute inflammatory response after coronary stenting non-pharmacological, through genetic analysis and cytokine, C reactive protein (CRP) and nitric oxide (NO), and correlate this response to the occurrence of events at nine months post-procedure. Patients undergoing angioplasty will be divided into two groups: group 1 (n = 55), will be administered at a dose of 40 mg of rosuvastatin and group 2 (control, n = 55), placebo, both orally three hours pre angioplasty. Blood sample will be taken with anticoagulant aortic and coronary sinus pre-stenting and 15 minutes after implantation. The aortic blood samples are subjected to complete blood count, measurement of C-reactive protein and analysis of gene expression IL-1, IL-6, IL-8, MCP-1 and TNF-± by reference laboratory. It will be aliquotted plasma from blood specimens of aorta and coronary sinus of the patient (4 samples) and subjected to measurement of nitric oxide with Griess reagent and stored at -20 ° C for cytokine and mediators (IL- 1, IL-6, IL-8, PAI-1, MCP-1, TNF-±) by ELISA. The participation of patients in the study will be through application of informed consent and informed. Patients will be followed clinically for nine months. (AU)