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Synthetic apolipoprotein A-I mimetic peptide 4F protects hearts and kidneys after myocardial infarction

Texto completo
Moreira, Roberto S. [1] ; Irigoyen, Maria C. [2] ; Capcha, Jose M. C. [1] ; Sanches, Talita R. [1] ; Gutierrez, Paulo S. [3] ; Garnica, Margoth R. [1] ; Noronha, Irene de L. [1] ; Andrade, Lucia [1]
Número total de Autores: 8
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Div Nephrol, Sch Med, Av Dr Arnaldo 455, 3 Andar, Sala 3310, BR-01246903 Sao Paulo, SP - Brazil
[2] Univ Sao Paulo, Heart Inst, Lab Hypertens, Sch Med, Sao Paulo - Brazil
[3] Univ Sao Paulo, Heart Inst, Lab Pathol, Sch Med, Sao Paulo - Brazil
Número total de Afiliações: 3
Tipo de documento: Artigo Científico
Citações Web of Science: 0

Patients undergoing coronary angiography after myocardial infarction (MI) often develop cardiac and renal dysfunction. We hypothesized that the apolipoprotein A-I mimetic peptide 4F (4F) would prevent those complications. Male Wistar rats were fed a high-cholesterol diet for 8 days. The rats were then anesthetized with isoflurane and randomly divided into five groups: a control group (sham-operated rats), and four groups of rats induced to MI by left coronary artery ligation, the rats in three of those groups being injected 6 h later, with the nonionic contrast agent iopamidol, 4F, and iopamidol plus 4F, respectively. At postprocedure hour 24, we performed the following experiments/tests (n = 8 rats/group): metabolic cage studies; creatinine clearance studies; analysis of creatinine, urea, sodium, potassium, triglycerides, total cholesterol, very low-, low- and high-density lipoproteins (VLDL, LDL, and HDL); immunohistochemistry; histomorphometry; Western blot analysis; and transmission electron microscopy. In another set of experiments (n = 8 rats/group), also performed at postprocedure hour 24, we measured mean arterial pressure, heart rate, heart rate variability, echocardiographic parameters, left ventricular systolic pressure, and left ventricular end-diastolic pressure. 4F protected against MI-induced increases in total cholesterol, triglycerides, and LDL; increased HDL levels; reversed autonomic and cardiac dysfunction; decreased the myocardial ischemic area; minimized renal and cardiac apoptosis; protected mitochondria; and strengthened endothelia possibly by minimizing Toll-like receptor 4 upregulation (thus restoring endothelial nitric oxide synthase protein expression) and by upregulating vascular endothelial growth factor protein expression. 4F-treated animals showed signs of cardiac neovascularization. The nitric oxide-dependent cardioprotection and renoprotection provided by 4F could have implications for post-MI treatment. (AU)

Processo FAPESP: 10/19012-0 - Avaliação da terapia com células-tronco hematopoiéticas na doença renal crônica em cães
Beneficiário:Lucia da Conceição Andrade
Linha de fomento: Auxílio à Pesquisa - Temático