FRANCISCO RAFAEL MARTINS LAURINDO
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina
LIM/64, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/64, Hospital das Clínicas, Faculdade de Medicina - Líder
10 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 10
- Endothelium-Dependent Vasodilation: Nitric Oxide and Other Mediators(2018) LAURINDO, F. R. M.; LIBERMAN, M.; FERNANDES, D. C.; LEITE, P. F.Vasodilation is the archetypal function of the endothelial cell and the discovery of paracrine-dependent vasorelaxation by endothelium-derived production of the gaseous mediator nitric oxide (NO) was revolutionary. NO mediates its regulatory vasorelaxing effects through guanilyl cyclase activation. Also, thiol S-nitrosation by NO is increasingly evident as an effector mechanism. Another important NO-related chemistry is its reaction with superoxide radicals, yielding peroxynitrite and related oxidant and nitrating species associated with toxic effects. Nitrogen oxides are storage forms of NO which can exert vasodilation in the presence of hemeproteins. NO generation is mediated by NO synthase enzymes (endothelial, neuronal, and inducible isoforms), which depict complex regulation dependent on cofactors. The absence of such cofactors can uncouple NO generation from electron transfer, generating superoxide. The endothelium additional promotes vasodilation, mainly of small resistance arteries, through endothelium-derived hyperpolarizing factor(s) such as hydrogen peroxide, epoximetabolites of arachidonic acid, and gap junctions. Hydrogen sulfide is a novel gaseous endothelium-derived vasodilator. Together, these mechanisms compose an integrative platform providing an endothelium-associated dilator tone. © 2018 Elsevier Inc. All rights reserved.
bookPart Endotélio na aterosclerose: formação da placa e complicações(2016) LUZ, Protásio Lemos da; CHAGAS, Antonio Carlos Palandri; LAURINDO, Francisco Rafael Martins- Endothelium in Atherosclerosis: Plaque Formation and Its Complications(2018) LUZ, P. L. da; CHAGAS, A. C. P.; DOURADO, P. M. M.; LAURINDO, F. R. M.Atherosclerosis refers to the slow process of plaque formation on the walls of the arteries and includes the deposit of fat and cellular debris in the inner wall of the arteries, inflammation, proliferative responses and apoptosis. Arteries become progressively thickened and often calcified. Typically, the atherosclerotic process begins in the first decades of life and progresses slowly. Aging and genetic susceptibility play a preponderant role in the evolution of atherosclerosis. The pathophysiological understanding of atherosclerosis has gone through several stages. Today, it is understood as an inflammatory/proliferative disease. Endothelial dysfunction plays a central role in the formation of atherosclerotic plaque, in its progression, and in complications. Therefore, the main objective of this chapter is to offer an integrated review of the main factors that participate in the formation of the atherosclerotic plaque with specific focus on the endothelium. © 2018 Elsevier Inc. All rights reserved.
bookPart Via redox de sinalização celular na disfunção endotelial e doença vascular(2016) LAURINDO, Francisco Rafael MartinsbookPart Biologia da parede do vaso(2016) LAURINDO, Francisco R. M.; ARAUJO, Thaís L. S.; FERNANDES, Denise C.bookPart Forças hemodinâmicas no endotélio: da mecanotransdução às implicações no desenvolvimento da aterosclerose(2016) FERNANDES, Denise C.; LAURINDO, Francisco Rafael Martins; ARAUJO, Thaís L. S.; TANAKA, Leonardo Y.bookPart Vasodilatação dependente do endotélio: óxido nítrico e outros mediadores(2016) LAURINDO, Francisco Rafael Martins; FERNANDES, Denise C.; LIBERMAN, Marcel; LEITE, Paulo Ferreira- Proteins Cross-talking with Nox Complexes: The Social Life of Noxes(2023) BESSA, T. C. de; LAURINDO, F. R. M.Nox NADPH Oxidases exhibit a basic organization comprising a catalytic transmembrane subunit closely regulated by canonical regulatory subunits, discussed in other chapters of this book. However, many additional proteins regulate the expression, assembly, structure, activity and subcellular traffic of Nox subunits. As such, they gravitate around Nox complexes and physically associate with at least one among the regulatory or catalytic subunits. Given that such associated proteins, in turn, exert canonical effects distinct from Nox regulation, they connect Nox function to physiological cell programs, mediating cross-talk to and from Noxes. This chapter provides a systematic overview of proteins for which the physical interaction with Noxes has been validated by “wet-lab” experiments. Such proteins support both stimulatory or inhibitory effects towards several aspects of Nox regulation and can be roughly classified as: (a) kinase-related organizers; (b) general organizers; (c) chaperone-like organizers; (d) RhoGTPase and/or cytoskeleton-related organizers; (e) scaffold proteins. In addition, we provide an overview of the Nox interactome “in silico”, indicating that Noxes cross-talk with their environment preferentially via interactive protein hubs associated with their regulatory, rather than catalytic subunits. Characterizing the roles of Nox-associated proteins is essential to provide an integrative understanding of Noxes within multiple cellular physiological contexts. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2023.
bookPart Síndrome coronariana aguda aspectos fisiopatológicos(2016) LIBERMAN, Marcel; FARIAS-SILVA, Elisângela; LAURINDO, Francisco Rafael Martins- Measurement of superoxide production and nadph oxidase activity by HPLC analysis of dihydroethidium oxidation(2017) FERNANDES, D. C.; GONçALVES, R. C.; LAURINDO, F. R. M.The fluorogenic probe dihydroethidium (DHE) is widely used for detecting intracellular superoxide. DHE oxidation by superoxide generates specifically the compound 2-hydroxyethidium (2-E+OH), so that 2-E+OH detection confers specificity to superoxide assessment among many other reactive oxygen species. However, DHE oxidation in biological systems leads to formation of other fluorescent products, particularly ethidium, usually formed at higher quantities than 2-E+OH. Since both 2-E+OH and ethidium are fluorescent, their identification and quantification is possible only after their physical separation by HPLC. Here we describe the detailed procedures for superoxide measurement in cells (adhered or not) and fresh tissues fragments, followed by acetonitrile extraction and simultaneous fluorescent detection of 2-E+OH and ethidium and absorbance detection of remaining unreacted DHE. In addition we report the use of DHE/HPLC for measuring NADPH oxidase activity in enriched-membrane fraction isolated from cells or tissues. These methods can improve accuracy and precision of quantitative superoxide measurements in biological samples. © Springer Science+Business Media LLC 2017.