MARGOTH RAMOS GARNICA
Índice h a partir de 2011
6
Projetos de Pesquisa
Unidades Organizacionais
LIM/29 - Laboratório de Nefrologia Celular, Genética e Molecular, Hospital das Clínicas, Faculdade de Medicina
2 resultados
Resultados de Busca
Agora exibindo 1 - 2 de 2
- Synthetic apolipoprotein A-I mimetic peptide 4F protects hearts and kidneys after myocardial infarction(2020) MOREIRA, Roberto S.; IRIGOYEN, Maria C.; CAPCHA, Jose M. C.; SANCHES, Talita R.; GUTIERREZ, Paulo S.; GARNICA, Margoth R.; NORONHA, Irene de L.; ANDRADE, LuciaPatients 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.
- Wharton's jelly-derived mesenchymal stem cells attenuate sepsis-induced organ injury partially via cholinergic anti-inflammatory pathway activation(2020) CAPCHA, Jose Manuel Condor; RODRIGUES, Camila Eleuterio; MOREIRA, Roberto de Souza; SILVEIRA, Marcelo Duarte; DOURADO, Paulo; SANTOS, Fernando dos; IRIGOYEN, Maria Claudia; JENSEN, Leonardo; GARNICA, Margoth Ramos; NORONHA, Irene L.; ANDRADE, Lucia; GOMES, Samirah AbreuSepsis induces organ dysfunction due to overexpression of the inflammatory host response, resulting in cardiopulmonary and autonomic dysfunction, thus increasing the associated morbidity and mortality. Wharton's jellyderived mesenchymal stem cells (WJ-MSCs) express genes and secrete factors with anti-inflammatory properties, neurological and immunological protection, as well as improve survival in experimental sepsis. The cholinergic anti-inflammatory pathway (CAP) is mediated by alpha 7-nicotinic acetylcholine receptors (alpha 7nAChRs). which play an important role in the control of systemic inflammation. We hypothesized that WJ-MSCs attenuate sepsis-induced organ injury in the presence of an activated CAP pathway. To confirm our hypothesis, we evaluated the effects of WJ-MSCs as a treatment for cardiopulmonary injury and on neuroimmunomodulation. Male Wistar rats were randomly divided into four groups: control (sham-operated); cecal ligation and puncture (CLP) alone; CL.P+WJ-MSCs (1 x 10(6) cells, at 6 h post-CLP); and CLP+methyllycaconifine (MLA)+WJ-MSCs (5 mg/kg body wt, at 53 h post-CLP, and 1 x 10(6) cells, at 6 h post-CLP. respectively). All experiments, including the assessment of echocardiographic parameters and heart rate variability, were performed 24 h after CLP. WJ-MSC treatment attenuated diastolic dysfunction and restored baroreflex sensitivity. WJ-MSCs also increased cardiac sympathetic and cardiovagal activity. WJ-MSCs reduced leukocyte infiltration and proinflammatory cytokines, effects that were abolished by administration of a selective alpha 7nAChR antagonist (MLA). In addition, WJ-MSC treatment also diminished apoptosis in the lungs and spleen. In cardiac and splenic tissue, WJ-MSCs downregulated alpha 7nAChR expression, as well as reduced the phospho-STAT3-tototal STAT3 ratio in the spleen. WJ-MSCs appear to protect against sepsis-induced organ injury by reducing systemic inflammation, at least in part, via a mechanism that is dependent on an activated CAP.