Karla Fernandes

Santa Casa de Belo Horizonte, Cidade de Minas, Minas Gerais, Brazil

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Publications (15)47.11 Total impact

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    ABSTRACT: Obesity is considered a subchronic inflammatory disease with high risk of comorbidity development. Obesity-associated inflammation originates from adipose tissue itself, which secretes a panel of inflammatory chemokines and cytokines. Therefore, we enrolled 23 obese women without comorbidity and evaluated if simvastatin 20 mg/day dose therapy for 6 weeks (n = 15) may modulate plasma levels of inflammatory CXCL-10, CCL-2, CXCL-9, CXCL-8, and CCL-5. A significant decrease of cholesterol and its fractions, triglycerides, and high-sensitivity C-reactive protein (hsCRP) after simvastatin treatment was observed when compared to placebo (n = 8). Chemokine plasma levels were unchanged by statin intake when compared to placebo. Although dyslipidemia biomarkers and hsCRP have been diminished by simvastatin, low chemokine amounts produced by healthy obese women do not seem to be altered by simvastatin anti-inflammatory activity.
    Inflammation 02/2015; 38(3). DOI:10.1007/s10753-014-0100-2 · 1.92 Impact Factor
  • Valeria Sandrim, Karla Fernandes, Ricardo Cavalli
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    ABSTRACT: A total of 24 preeclampsia was enrolled. All pregnant were Caucasian, non-smoker, BMI <30 Kg/m2. At the time of clinic attendance, venous blood samples were collected (EDTA), tubes centrifuged and plasma samples were stored at -70°C. sFLT-1 plasma levels were measured by ELISA (DVR100B). MiRs were extracted from plasma using the miRNeasy Serum/Plasma Kit. Samples from three preeclampsia presenting the highest level of sFLT-1 and three presenting the lowest levels were choose to performed a screening using the Human Plasma miRNA PCR array (MIHS-106Z) following the manufacturer's protocol. After screening individual miRNAs were quantified by miScript SYBR Green qRT-PCR assays using specifics primers. Among 84 miRNAs evaluated by PCR-array, 4 were differentially expressed between groups considering a fold-change ⩾3.0: miR-195-5p, miR-16-5p and miR-19b-3p were more expressed in high group and miR-375 in low group. The next step was performed real-time qRT-PCR in all samples (n=24) and verify correlations with sFLT-1. We use two extremes of analysis: 50% and 25% of sFLT-1 levels in the 24 samples (n=12 in low and n=12 in high group considering 50% analysis; and n=6 in low and n=6 in high group considering 25% analysis). The result is demonstrated in Figure. We concluded that miR195-5p is associated with higher levels of sFLT-1 in preeclampsia. Financial Support: Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). V. Sandrim: None. K. Fernandes: None. R. Cavalli: None. Copyright © 2014.
    01/2015; 5(1):60. DOI:10.1016/j.preghy.2014.10.117
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    ABSTRACT: ProblemAugmented levels of IL-1ß have been pointed out as an important pathogenic factor for preeclampsia development. Inflammasome is the cytoplasmic complex responsible for pro-IL1ß cleavage and IL-1ß secretion. Aim of the study was to evaluate the association between polymorphisms in inflammasome' genes and preeclampsia.Method of studySelected polymorphisms in inflammasome genes (NLRP1, NLRP3, CARD8, and IL1B) were analyzed in 286 Brazilian women with and 309 without preeclampsia.Results and ConlclusionsThe NLRP1 variant rs12150220 (L155H) was associated with the development of preeclampsia (OR = 1.58), suggesting a role of this inflammasome receptor in the pathogenesis of this multifactorial disorder.
    American Journal Of Reproductive Immunology 12/2014; 73(6). DOI:10.1111/aji.12353 · 3.32 Impact Factor
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    ABSTRACT: Evidence indicates an impairment of nitric oxide (NO) in obesity. Statins present pleiotropic effects independently of cholesterol-lowering, including increasing of eNOS expression and antioxidant effects. We evaluated the effects of simvastatin treatment at 45 days on circulating nitrite (NO marker) and TBARS-MDA levels in obese women without comorbidities (hypertension, diabetes and dyslipidemia). Moreover, we verified whether obese women carrying the C variant of T(-786)C polymorphism located in eNOS may have increased levels of nitrite after treatment compared to TT genotype. After simvastatin treatment, while the plasma nitrite levels increased 42% (P=0.0008), the TBARS-MDA levels reduced 58% (P=0.0069). We observed increased levels of nitrite in both groups of genotypes (TT vs TC+CC); however, rise in C-allele carriers was 60% comparing with 44% in TT. Our results demonstrated a restoration of nitrite levels in obese women treated with simvastatin, which is modulated by T(-786)C polymorphism.
    Nitric Oxide 07/2013; 33. DOI:10.1016/j.niox.2013.07.005 · 3.18 Impact Factor
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    ABSTRACT: We have described that MMP-9 C(-1562)T and (CA)(n) polymorphisms contribute to multiple sclerosis (MS). Here, we evaluate whether plasma MMP-9 levels are related to disease severity, drug therapy resistance and polymorphisms. For sub-study 1, 36 patients with MS and 35 controls were recruited. For sub-study 2, 88 individuals (53 patients and 35 controls) were included in a cross-sectional analysis. MS patients presented higher MMP-9 activity (1.4±0.18 versus 0.93±0.18A.U. for control, P<0.05). Drug-therapy resistant individuals exhibited increased MMP-9 activity (1.96±0.25 versus 1.21±0.09A.U. for non-resistant patients). EDSS score was also related to MMP-9 levels. The CT+TT and HH genotypes had higher MMP-9 levels as compared to patients carrying the CC and LL. Drug therapy resistance, disease severity, MMP-9 plasma activity and polymorphisms are associated with MS.
    Journal of neuroimmunology 05/2012; 249(1-2):56-9. DOI:10.1016/j.jneuroim.2012.04.001 · 2.79 Impact Factor
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    ABSTRACT: The adipose tissue expansion is accompanied by remodeling of extracellular matrix performed by matrix metalloproteinases (MMPs). Higher plasma and tissue MMP-9 levels are found in obese; therefore, we evaluated if the functional C(-1562)T polymorphism (rs3918242) located in promoter region of the MMP-9 gene is associated with obesity in women. We studied 112 lean and 114 obese women. Plasma MMP-9 and tissue inhibitor of MMP-9 (TIMP)-1 were measured using enzyme-linked immunosorbent assay. We found different genotype frequencies between lean and obese women (p=0.008), prevailing T-allele in obese (2.3-fold). However, although obese women present higher levels of plasma MMP-9, lack of modulation by the polymorphism was found (all p>0.05). Our findings suggest that C(-1562)T polymorphism may contribute to pathogenetic mechanisms involved in the development of obesity in women.
    DNA and cell biology 02/2012; 31(6):1054-7. DOI:10.1089/dna.2011.1526 · 1.99 Impact Factor
  • Karla S Fernandes, Valéria C Sandrim
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    ABSTRACT: The increase in plasminogen activator inhibitor type 1 (PAI-1) has been described as a risk factor to thrombosis-related diseases. In addition, it has been demonstrated that the variant 4G of polymorphism 4G/5G located in promoter region of PAI-1 gene is associated with higher PAI-1 levels. We investigate the role of this polymorphism on circulating PAI-1 concentration in a population of 57 obese women (23%, 4G/4G; 49%, 4G/5G and 28%, 5G/5G genotypes). Our results demonstrate a genotype-specific modulation on PAI-1 levels in obese women, thus 5G/5G genotype presented significantly lower levels of plasma PAI-1 when compared to 4G/4G group (46 ± 19 ng/mL vs. 63 ± 13 ng/mL, respectively). Our findings indicate that obese carriers of 4G/4G genotype may have increased risk to develop thrombotic diseases.
    Molecular and Cellular Biochemistry 01/2012; 364(1-2):299-301. DOI:10.1007/s11010-012-1230-1 · 2.39 Impact Factor
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    ABSTRACT: Multiple sclerosis (MS) is an autoimmune disease causing severe neurological disability. This study was carried out in order to determine whether the MMP-9 C(-1562)T and (CA)(13-25) polymorphisms are associated with MS. A total of 165 patients (92 whites/73 mulattos) and 191 controls (96 whites/95 mulattos) were enrolled in the study. While no difference in C(-1562)T polymorphism was observed between MS and healthy subjects, (CA)(n) genotypes and alleles were associated with MS. Moreover, the haplotypes are not associated with MS but seem to be relevant to the clinical status of MS. Thus the (CA)(n) polymorphism may contribute to MS susceptibility, but C(-1562)T and (CA)(n) haplotypes may modulate disease severity.
    Journal of neuroimmunology 08/2009; 214(1-2):128-31. DOI:10.1016/j.jneuroim.2009.07.004 · 2.79 Impact Factor
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    ABSTRACT: IL-23/IL-17-induced neutrophil recruitment plays a pivotal role in rheumatoid arthritis (RA). However, the mechanism of the neutrophil recruitment is obscure. Here we report that prostaglandin enhances the IL-23/IL-17-induced neutrophil migration in a murine model of RA by inhibiting IL-12 and IFN gamma production. Methylated BSA (mBSA) and IL-23-induced neutrophil migration was inhibited by anti-IL-23 and anti-IL-17 antibodies, COX inhibitors, IL-12, or IFNgamma but was enhanced by prostaglandin E(2) (PGE(2)). IL-23-induced IL-17 production was increased by PGE(2) and suppressed by COX-inhibition or IL-12. Furthermore, COX inhibition failed to reduce IL-23-induced neutrophil migration in IL-12- or IFNgamma-deficient mice. IL-17-induced neutrophil migration was not affected by COX inhibitors, IL-12, or IFNgamma but was inhibited by MK886 (a leukotriene synthesis inhibitor), anti-TNFalpha, anti-CXCL1, and anti-CXCL5 antibodies and by repertaxin (a CXCR1/2 antagonist). These treatments all inhibited mBSA- or IL-23-induced neutrophil migration. IL-17 induced neutrophil chemotaxis through a CXC chemokines-dependent pathway. Our results suggest that prostaglandin plays an important role in IL-23-induced neutrophil migration in arthritis by enhancing IL-17 synthesis and by inhibiting IL-12 and IFNgamma production. We thus provide a mechanism for the pathogenic role of the IL-23/IL-17 axis in RA and also suggest an additional mechanism of action for nonsteroidal anti-inflammatory drugs.
    Proceedings of the National Academy of Sciences 05/2009; 106(14):5954-9. DOI:10.1073/pnas.0812782106 · 9.81 Impact Factor
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    ABSTRACT: Lead exposure increases blood pressure (BP) by unknown mechanisms. Many recent studies have shown the involvement of matrix metalloproteinases (MMPs) in hypertension, particularly MMP-2. In this work, we have examined whether MMP-2 levels increase with lead-induced increase in BP. We have also investigated whether doxycycline (an MMP inhibitor) affects these alterations. To this end, rats were exposed to lead (90 ppm) and treated with doxycycline or vehicle for 8 weeks. Similar aortic and whole blood lead levels were found in lead-exposed rats treated with either doxycycline or vehicle. Lead-induced increases in BP and aortic MMP-2 levels (activity, protein, and mRNA) were blunted by doxycycline. Doxycycline also prevented lead-induced increases in the MMP-2/TIMP-2 mRNA ratio. No significant changes in vascular reactivity or morphometric parameters were found. In conclusion, lead exposure increases BP and vascular MMP-2, which is blunted by doxycycline. This observation suggests that MMP-2 may play a role in lead-induced increases in BP.
    Archives of Toxicology 11/2008; 83(5):439-49. DOI:10.1007/s00204-008-0363-1 · 5.08 Impact Factor
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    ABSTRACT: Abnormal matrix metalloproteinases (MMPs) activity causes cardiovascular diseases. Because hyperglycemia increase MMPs activities through increased oxidative stress, we hypothesized that antioxidant effects produced by lercanidipine could attenuate the increases in MMP-2 expression/activity in diabetic rats. Control and diabetic (alloxan-induced diabetes) rats received lercanidipine 2.5 mg/kg/day (or tap water) starting three weeks after alloxan (or vehicle) injections. Blood pressure was monitored weekly. After six weeks of treatment, vascular reactivity and structural changes were assessed in aortic rings. MMP-2 levels were determined by gelatin zymography, and MMP-2/tissue inhibitor of metalloproteinases (TIMP)-2 mRNA levels were determined by quantitative real time RT-PCR. Plasma thiobarbituric acid reactive substances concentrations were determined by fluorimetry. Lercanidipine produced antihypertensive effects (201+/-5 vs. 163+/-7 mm Hg in diabetic rats untreated and treated with lercanidipine, respectively; P<0.01) and reversed the impairment in endothelium-dependent vasorelaxation in diabetic rats. Increased MMP-2 and Pro-MMP-2 levels were found in the aortas of diabetic rats (both P<0.001). Lercandipine attenuated the increases in oxidative stress and in MMP-2 (both P<0.05). While diabetes induced no major structural changes, it caused a 16-fold increase in the ratio of MMP-2/TIMP-2 mRNA expression, which was completely reversed by lercanidipine (both P<0.001). These results show that antioxidant and beneficial vascular effects produced by lercanidipine in diabetic rats are associated with reversion of the imbalance in vascular MMP-2/TIMP-2 expression.
    European Journal of Pharmacology 10/2008; 599(1-3):110-6. DOI:10.1016/j.ejphar.2008.10.007 · 2.68 Impact Factor
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    ABSTRACT: Increased expression/activity of matrix metalloproteinases (MMPs), especially MMP-2, plays a role in the vascular alterations induced by hypertension, and increased oxidative stress is a major factor activating MMPs. Here, we hypothesized that lercanidipine, a calcium channel blocker, could attenuate the increases in oxidative stress and MMP-2 expression/activity in the two-kidney, one-clip (2K-1C) hypertensive rats. Sham-operated or 2K-1C hypertension rats were treated with lercanidipine 2.5 mg/kg/day (or vehicle) starting three weeks after hypertension was induced. Systolic blood pressure was monitored weekly. After five weeks of treatment, aortic rings were isolated to assess endothelium-dependent and independent relaxations. Quantitative morphometry of structural changes in the aortic wall were studied in hematoxylin/eosin sections. Aortic MMP-2 levels were determined by gelatin zymography. Aortic MMP-2/tissue inhibitor of metalloproteinases (TIMP)-2 mRNA levels were determined by quantitative real-time RT-PCR. Plasma thiobarbituric acid reactive substances concentrations were determined using a fluorometric method. Lercanidipine attenuated 2K-1C hypertension (224+/-12 versus 183+/-11 mm Hg in 2K-1C rats and 2K-1C + Lercandipine rats, respectively; P<0.01) and prevented the reduction in endothelium-dependent vasorelaxation found in 2K-1C rats. Increased MMP-2 and Pro-MMP-2 levels were found in the aortas of 2K-1C rats (all P<0.05). Lercandipine attenuated 2K-1C-induced increases in MMP-2 by more than 60% and blunted 2K-1C-induced increases in oxidative stress (both P<0.001). While hypertension-induced significant aortic wall hypertrophy and approximately 9-fold increases in the ratio of MMP-2/TIMP-2 mRNA expression (both P<0.05), lercandipine did not affect these changes. These results suggest that lercanidipine produces antihypertensive effects and reverses the endothelial dysfunction associated with 2K-1C hypertension, probably through mechanisms involving antioxidant effects leading to lower MMP-2 activation.
    European Journal of Pharmacology 09/2008; 591(1-3):224-30. DOI:10.1016/j.ejphar.2008.06.096 · 2.68 Impact Factor
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    ABSTRACT: Altered activity of matrix metalloproteinases (MMPs) is implicated in the vascular remodeling of hypertension. We examined whether increased MMP-2 expression/activity plays a role in the vascular remodeling and dysfunction found in the two-kidney, one-clip (2K-1C) hypertension. Sham operated or 2K-1C hypertension rats were treated with doxycycline 30mg/(kgday) (or vehicle). Systolic blood pressure was monitored weekly. After 8 weeks of treatment, aortic rings were isolated to assess endothelium-dependent and independent relaxations. Quantitative morphometry of structural changes, collagen, and elastin contents in the aortic wall were studied in hematoxylin/eosin, Sirius Red, and Orceine stained aortic sections, respectively. Aortic MMP-2 levels were determined by gelatin zymography and aortic MMP-2 proteolytic activity was measured using DQ gelatin as the substrate after MMP-2 was captured by a specific antibody and immobilized on a microplate. Aortic MMP-2/tissue inhibitor of metalloproteinases (TIMP)-2 mRNA levels were determined by real time RT-PCR. Doxycycline attenuated 2K-1C hypertension (215+/-8mmHg versus 167+/-13mmHg in 2K-1C rats and 2K-1C+doxy rats, respectively; P<0.01) and prevented the 35% reduction in endothelium-dependent vasorelaxation found in 2K-1C rats. Doxycycline prevented the increases in media thickness, and was associated with lower media/lumen and cross-sectional areas (all P<0.01). Doxycycline also prevented excessive collagen and elastin deposition in the vascular wall. Increased MMP-2 and Pro-MMP-2 levels and MMP-2 activity were found in the aortas of 2K-1C rats (all P<0.05). A 21-fold increase (P<0.001) in the ratio of MMP-2/TIMP-2 mRNA expression was found in the 2K-1C group, whereas this ratio remained unaltered in 2K-1C+doxy rats. Our results suggest that MMP-2 plays a role in 2K-1C hypertension and its structural and functional vascular changes, which were attenuated by doxycycline.
    Atherosclerosis 06/2008; 198(2):320-31. DOI:10.1016/j.atherosclerosis.2007.10.011 · 3.97 Impact Factor
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    ABSTRACT: Neutrophils are thought to play an important role in the tissue damage observed in various autoimmune diseases. Chemokines, cytokines and leukotrienes have recognized roles in the orchestration of neutrophil migration. We have recently shown that antigen-induced neutrophil migration into the peritoneum of immunized mice is mediated by macrophage-inflammatory protein (MIP)-1alpha which interacts with CCR1 and induces the sequential release of TNF-alpha and leukotriene B(4) (LTB(4)). The present study investigates the role of MIP-2 and CXCR2 in the cascade of events leading to mediator generation and neutrophil influx. Antigen challenge of immunized mice induced the expression of CXCR2 and the production of KC and MIP-2 proteins. Antigen-induced neutrophil migration was inhibited by a CXCR2 receptor antagonist (repertaxin) or an anti-MIP-2 antibody, but not by an anti-KC antibody. Administration of MIP-2 promoted a dose-dependent neutrophil migration in naive mice which was inhibited by repertaxin, anti-TNF-alpha, anti-MIP-1alpha antibodies or by MK886 (leukotriene synthesis inhibitor). MIP-2 administration induced the release of MIP-1alpha, TNF-alpha and LTB(4), and the release of the latter two was inhibited by anti-MIP-1alpha antibody treatment. Our studies highlight the intricate balance between mediator production and action during an immune-mediated inflammatory response and suggest a mediator cascade leading to neutrophil influx following antigen challenge of immunized mice: MIP-2 --> MIP-1alpha --> TNF-alpha --> LTB(4).
    European Journal of Immunology 08/2006; 36(8):2025-34. DOI:10.1002/eji.200636057 · 4.52 Impact Factor

Publication Stats

297 Citations
47.11 Total Impact Points


  • 2012–2015
    • Santa Casa de Belo Horizonte
      Cidade de Minas, Minas Gerais, Brazil
  • 2006–2012
    • University of São Paulo
      • Ribeirão Preto School of Medicine (FMRP)
      San Paulo, São Paulo, Brazil