VIVIANE ZORZANELLI ROCHA GIRALDEZ
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina - Médico
6 resultados
Resultados de Busca
Agora exibindo 1 - 6 de 6
- Activation of prostaglandin E-2-EP4 signaling reduces chemokine production in adipose tissue(2015) TANG, Eva H. C.; CAI, Yin; WONG, Chi Kin; ROCHA, Viviane Z.; SUKHOVA, Galina K.; SHIMIZU, Koichi; XUAN, Ge; VANHOUTTE, Paul M.; LIBBY, Peter; XU, AiminInflammation of adipose tissue induces metabolic derangements associated with obesity. Thus, determining ways to control or inhibit inflammation in adipose tissue is of clinical interest. The present study tested the hypothesis that in mouse adipose tissue, endogenous prostaglandin E-2 (PGE(2)) negatively regulates inflammation via activation of prostaglandin E receptor 4 (EP4). PGE(2) (5-500nM) attenuated lipopolysaccharide-induced mRNA and protein expression of chemokines, including interferon--inducible protein 10 and macrophage-inflammatory protein-1 in mouse adipose tissue. A selective EP4 antagonist (L161,982) reversed, and two structurally different selective EP4 agonists [CAY10580 and CAY10598] mimicked these actions of PGE(2). Adipose tissue derived from EP4-deficient mice did not display this response. These findings establish the involvement of EP4 receptors in this anti-inflammatory response. Experiments performed on adipose tissue from high-fat-fed mice demonstrated EP4-dependent attenuation of chemokine production during diet-induced obesity. The anti-inflammatory actions of EP4 became more important on a high-fat diet, in that EP4 activation suppressed a greater variety of chemokines. Furthermore, adipose tissue and systemic inflammation was enhanced in high-fat-fed EP4-deficient mice compared with wild-type littermates, and in high-fat-fed untreated C57BL/6 mice compared with mice treated with EP4 agonist. These findings provide in vivo evidence that PGE(2)-EP4 signaling limits inflammation. In conclusion, PGE(2), via activation of EP4 receptors, functions as an endogenous anti-inflammatory mediator in mouse adipose tissue, and targeting EP4 may mitigate adipose tissue inflammation.
- CXCR3 Controls T-Cell Accumulation in Fat Inflammation(2014) ROCHA, Viviane Zorzanelli; FOLCO, Eduardo J.; OZDEMIR, Cafer; SHEIKINE, Yuri; CHRISTEN, Thomas; SUKHOVA, Galina K.; TANG, Eva H. C.; BITTENCOURT, Marcio Sommer; SANTOS, Raul D.; LUSTER, Andrew D.; COHEN, David E.; LIBBY, PeterObjective-Obesity associates with increased numbers of inflammatory cells in adipose tissue (AT), including T cells, but the mechanism of T-cell recruitment remains unknown. This study tested the hypothesis that the chemokine (C-X-C motif) receptor 3 (CXCR3) participates in T-cell accumulation in AT of obese mice and thus in the regulation of local inflammation and systemic metabolism. Approach and Results-Obese wild-type mice exhibited higher mRNA expression of CXCR3 in periepididymal AT-derived stromal vascular cells compared with lean mice. We evaluated the function of CXCR3 in AT inflammation in vivo using CXCR3-deficient and wild-type control mice that consumed a high-fat diet. Periepididymal AT from obese CXCR3-deficient mice contained fewer T cells than obese controls after 8 and 16 weeks on high-fat diet, as assessed by flow cytometry. Obese CXCR3-deficient mice had greater glucose tolerance than obese controls after 8 weeks, but not after 16 weeks. CXCR3-deficient mice fed high-fat diet had reduced mRNA expression of proinflammatory mediators, such as monocyte chemoattractant protein-1 and regulated on activation, normal T cell expressed and secreted, and anti-inflammatory genes, such as Foxp3, IL-10, and arginase-1 in periepididymal AT, compared with obese controls. Conclusions-These results demonstrate that CXCR3 contributes to T-cell accumulation in periepididymal AT of obese mice. Our results also suggest that CXCR3 regulates the accumulation of distinct subsets of T cells and that the ratio between these functional subsets across time likely modulates local inflammation and systemic metabolism.
- Cardiovascular disease onset in old people with severe hypercholesterolemia(2023) COUTINHO, Elaine R.; MINAME, Marcio H.; ROCHA, Viviane Z.; BITTENCOURT, Marcio S.; JANNES, Cinthia E.; KRIEGER, Jose E.; PEREIRA, Alexandre C.; SANTOS, Raul D.Background and aims: Familial hypercholesterolemia (FH) variants are associated with higher atherosclerotic cardiovascular disease risk (ASCVD) even when compared with other forms of severe hypercholesterolemia, especially in young people. Lipid lowering therapies (LLT) may change hypercholesterolemia natural history. This study aimed at evaluating factors associated with occurrence of ASCVD in old severe hypercholesterolemics diagnosed or not with FH and undergoing LLT.Methods: Hypercholesterolemic individuals >= 60 years participating on a genetic cascade screening for FH were divided in 4 groups (2 x 2) according to the presence (variant+) or not (variant-) of FH genetic variants and previous ASCVD (ASCVD+ and ASCVD-). Biomarkers associated with new incident ASCVD events were tested using Cox models. Continuous data shown as medians (%25; %75).Results: From 4,111 genotyped individuals, 377 (9.1%) were elderly [age 66 (63; 71) years], 28.9% males, 42.7% variant+, 32.1% with previous ASCVD, LLT duration 9 (5; 16) years, and on treatment LDL-cholesterol 144 (109; 200) mg/dL. After 4.8 (7; 3) years of follow up there were 47 incident events (12.4%, 2.7% patient/year). The annualized event rates were 0.8% (95% CI 0.36%; 1.70%), 2.3% (95% CI 1.3%; 4.1%), 5.2% (95% CI 2.8%; 9.7%) and 6.3% (95% CI 4.0%; 10.0%) respectively for groups variant-/ASCVD-, variant+/ASCVD-, variant-/ ASCVD+ and, variant+/ASCVD+ (p log rank p < 0.001). Only presence of previous ASCVD was independently associated with incident ASCVD [hazard ratio 3.236 (95%CI 1.497-6.993, p = 0.003)]. No interaction was found for previous ASCVD and variants.Conclusions: In old severe hypercholesterolemic individuals undergoing long-term LLT previous ASCVD was associated with incident events while FH causing variants were not.
- Molecular Mechanisms of the Arterial Wall in Acute Coronary Syndromes(2018) SOUZA, B. B. de; ARAúJO, H. A.; GIRALDEZ, V. Z. R.; LIBBY, P.; GIRALDEZ, R. R. C. V.The endothelium plays a central role in vascular homeostasis. Indeed, when dysfunctional, the endothelium governs the genesis of atherosclerotic disease, mediating the relationship between cardiovascular risk factors (such as smoking, hypertension, dyslipidemia, and diabetes) and the initiation and evolution of atherosclerotic plaque. Despite the relevance of the endothelium in the insidious atherosclerotic process, it has received limited attention in the context of acute atheroma complications, as ruptures of the fibrous cap of lipid-rich plaques have dominated discussions of the major causes of acute coronary syndromes (ACS). Yet, recent studies have shown that superficial erosion may be rising as a cause of ACS while the prevalence of plaque rupture is waning. The term “erosion” suggests that a dysfunctional or absent layer of endothelium promotes thrombosis, but probing the mechanisms of such erosive events has been scarce. This chapter considers the potential pathophysiologic pathways that promote superficial erosion and discusses the involvement of the endothelium in nonatherosclerotic causes of ACS and in the vascular events following ACS. © 2018 Elsevier Inc. All rights reserved.
- CTHRSSVVC Peptide as a Possible Early Molecular Imaging Target for Atherosclerosis(2016) SILVA, Rosemeire A.; GIORDANO, Ricardo J.; GUTIERREZ, Paulo S.; ROCHA, Viviane Z.; RUDNICKI, Martina; KEE, Patrick; ABDALLA, Dulcineia S. P.; PUECH-LEAO, Pedro; CARAMELLI, Bruno; ARAP, Wadih; PASQUALINI, Renata; MENEGHETTI, Jose C.; MARQUES, Fabio L. N.; KHOOBCHANDANI, Menka; KATTI, Kattesh V.; LUGAO, Ademar B.; KALIL, JorgeThe purpose of our work was to select phages displaying peptides capable of binding to vascular markers present in human atheroma, and validate their capacity to target the vascular markers in vitro and in low-density lipoprotein receptor knockout (LDLr-/-) mouse model of atherosclerosis. By peptide fingerprinting on human atherosclerotic tissues, we selected and isolated four different peptides sequences, which bind to atherosclerotic lesions and share significant similarity to known human proteins with prominent roles in atherosclerosis. The CTHRSSVVC-phage peptide displayed the strongest reactivity with human carotid atherosclerotic lesions (p < 0.05), when compared to tissues from normal carotid arteries. This peptide sequence shares similarity to a sequence present in the fifth scavenger receptor cysteine-rich (SRCR) domain of CD163, which appeared to bind to CD163, and subsequently, was internalized by macrophages. Moreover, the CTHRSSVVC-phage targets atherosclerotic lesions of a low-density lipoprotein receptor knockout (LDLr-/-) mouse model of atherosclerosis in vivo to High-Fat diet group versus Control group. Tetraazacyclododecane-1,4,7,10-tetraacetic acid-CTHRSSVVC peptide (DOTA-CTHRSSVVC) was synthesized and labeled with (InCl3)-In-111 in >95% yield as determined by high performance liquid chromatography (HPLC), to validate the binding of the peptide in atherosclerotic plaque specimens. The results supported our hypothesis that CTHRSSVVC peptide has a remarkable sequence for the development of theranostics approaches in the treatment of atherosclerosis and other diseases.
- All roads lead to IL-6: A central hub of cardiometabolic signaling(2018) LIBBY, Peter; ROCHA, Viviane Zorzanelli