RAUL CAVALCANTE MARANHAO
Projetos de Pesquisa
Unidades Organizacionais
FBC, FCF - Docente
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/31 - Laboratório de Genética e Hematologia Molecular, Hospital das Clínicas, Faculdade de Medicina
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/31 - Laboratório de Genética e Hematologia Molecular, Hospital das Clínicas, Faculdade de Medicina
8 resultados
Resultados de Busca
Agora exibindo 1 - 8 de 8
- What is new in familial hypercholesterolemia?(2014) SANTOS, Raul D.; MARANHAO, Raul C.Purpose of reviewThe purpose of this review is to describe advances in the diagnosis, cause, metabolism, risk factors for atherosclerosis, and treatment of familial hypercholesterolemia.Recent findingsHeterozygous familial hypercholesterolemia is almost four-fold more frequent than previously thought and is associated with 10-fold to 13-fold risk of cardiovascular disease comparing with normolipidemics. LDL receptor (LDLR) dysfunction and LDL-cholesterol (LDL-C) accumulation disturb the metabolism of other lipoprotein classes, such as chylomicrons and remnants and HDL. Next-generation sequencing can improve familial hypercholesterolemia molecular diagnosis due to its better performance and lower costs than usual techniques. Despite this, roughly 40% of familial hypercholesterolemia patients do not present mutations on the LDLR, apolipoprotein B, or proprotein convertase subtilisin/kexin type 9 genes. Many individuals with familial hypercholesterolemia phenotype have polygenic instead of monogenic cause of their elevated LDL-C concentrations. Individuals with familial hypercholesterolemia show elevated burden of subclinical atherosclerosis. The intensity of atherosclerosis burden is associated with the severity of LDLR mutation rather than maternal or paternal heritability. Newer-approved and on-development medications that reduce LDL-C hold promise for preventing cardiovascular disease in familial hypercholesterolemia.SummaryFamilial hypercholesterolemia is frequent and currently underdiagnosed and undertreated, but effective cascade screening programs and early and intensive LDL-C lowering can change this picture and the natural history of the disease.
- Lipoprotein removal mechanisms and aging: implications for the cardiovascular health of the elderly(2020) MARANHAO, Raul C.; PALA, Daniela; FREITAS, Fatima R.Purpose of review The speed of removal from the plasma of apolipoprotein B-containing lipoproteins, for example, chylomicrons, VLDL and LDL is determinant of the plasma concentration of these lipoproteins, is influenced by genetic features and ambient factors, and has implications in atherogenesis. As aging increases the clinical complications of atherosclerosis, it is important to appraise the status of the removal mechanisms in elderly individuals. Recent findings Removal of triglyceride-rich lipoproteins remnants is delayed but the triglyceride breakdown is unchanged in elderly individuals. The discovery of PCSK9, enzyme that degrades LDL receptors, and the recent observation that PCSK9 is elevated in the elderly raises another hypothesis to account for the increased LDL-cholesterol levels in the elderly. The removal of cholesterol from cells by HDL, the first step of cholesterol reverse transport is also less efficient in the elderly, which may compromise the body cholesterol homeostasis. Aging determines reduction of the efficiency of lipoprotein plasma removal mechanisms, which is implicated in increased incidence of cardia complications. Moreover, aging is frequently accompanied by physical activity reduction, weight gain, and metabolic disturbances that can further decrease the efficacy of the removal mechanisms. This knowledge is important for promoting cardiovascular health in the elderly and prolonging survival.
- Nanotechnology for Medical and Surgical Glaucoma Therapy-A Review(2020) OCCHIUTTO, Marcelo Luis; MARANHAO, Raul C.; COSTA, Vital Paulino; KONSTAS, Anastasios G.Glaucoma is the second leading cause of blindness worldwide. Even though significant advances have been made in its management, currently available antiglaucoma therapies suffer from considerable drawbacks. Typically, the success and efficacy of glaucoma medications are undermined by their limited bioavailability to target tissues and the inadequate adherence demonstrated by patients with glaucoma. The latter is due to a gradual decrease in tolerability of lifelong topical therapies and the significant burden to patients of prescribed stepwise antiglaucoma regimens with frequent dosing which impact quality of life. On the other hand, glaucoma surgery is restricted by the inability of antifibrotic agents to efficiently control the wound healing process without causing severe collateral damage and long-term complications. Evolution of the treatment paradigm for patients with glaucoma will ideally include prevention of retinal ganglion cell degeneration by the successful delivery of neurotrophic factors, anti-inflammatory drugs, and gene therapies. Nanotechnology-based treatments may surpass the limitations of currently available glaucoma therapies through optimized targeted drug delivery, increased bioavailability, and controlled release. This review addresses the recent advances in glaucoma treatment strategies employing nanotechnology, including medical and surgical management, neuroregeneration, and neuroprotection.
- Lipoproteína (a): Estrutura, Metabolismo, Fisiopatologia e Implicações Clínicas(2014) MARANHAO, Raul Cavalcante; CARVALHO, Priscila Oliveira; STRUNZ, Celia Cassaro; PILEGGI, FulvioThe chemical structure of lipoprotein (a) is similar to that of LDL, from which it differs due to the presence of apolipoprotein (a) bound to apo B100 via one disulfide bridge. Lipoprotein (a) is synthesized in the liver and its plasma concentration, which can be determined by use of monoclonal antibody-based methods, ranges from < 1 mg to > 1,000 mg/dL. Lipoprotein (a) levels over 20-30 mg/dL are associated with a two-fold risk of developing coronary artery disease. Usually, black subjects have higher lipoprotein (a) levels that, differently from Caucasians and Orientals, are not related to coronary artery disease. However, the risk of black subjects must be considered. Sex and age have little influence on lipoprotein (a) levels. Lipoprotein (a) homology with plasminogen might lead to interference with the fibrinolytic cascade, accounting for an atherogenic mechanism of that lipoprotein. Nevertheless, direct deposition of lipoprotein (a) on arterial wall is also a possible mechanism, lipoprotein (a) being more prone to oxidation than LDL. Most prospective studies have confirmed lipoprotein (a) as a predisposing factor to atherosclerosis. Statin treatment does not lower lipoprotein (a) levels, differently from niacin and ezetimibe, which tend to reduce lipoprotein (a), although confirmation of ezetimibe effects is pending. The reduction in lipoprotein (a) concentrations has not been demonstrated to reduce the risk for coronary artery disease. Whenever higher lipoprotein (a) concentrations are found, and in the absence of more effective and well-tolerated drugs, a more strict and vigorous control of the other coronary artery disease risk factors should be sought.
- Advances in non-invasive drug delivery for atherosclerotic heart disease(2015) MARANHAO, Raul C.; TAVARES, Elaine R.Introduction: Apart from statins, anti-platelet agents and invasive procedures, the anti-atherosclerotic medical weaponry for coronary heart disease (CHD) is scarce and only partially protects CHD patients from major adverse cardiac events. Areas covered: Several novel non-invasive strategies are being developed to widen the therapeutic options. Among them, drug delivery tools were tested in vivo encompassing liposomes, micelles, polymeric, metallic and lipid nano-particles used as carriers of statins, corticosteroids, a bisphosphonate, a glitazone, anti-cancer agents, a mycotoxin, a calcium channel blocker and a compound of traditional Chinese medicine. All preparations improved parameters related to atherosclerotic lesions induced in rabbits, rats and mice and reduced neointima formation in experiments aiming to prevent post-stenting restenosis. In subjects submitted to percutaneous coronary intervention, nano-particle formulations of paclitaxel and alendronate showed safety but are still not conclusive regarding in-stent late loss. The experience of our group in atherosclerotic rabbits treated with non-protein lipid nanoparticles associated with anti-cancer drugs such as paclitaxel, etoposide and methotrexate is summarized, and preliminary safety data in CHD patients are anticipated. Expert opinion: Taken together, these studies show that non-invasive drug-delivery systems may become promising tools to rescue CHD patients from the risks of severe and life-threatening lesions that should be more energetically treated.
- HDL Metabolism and Atheroprotection: Predictive Value of Lipid Transfers(2014) MARANHAO, Raul C.; FREITAS, Fatima R.High-density lipoprotein (HDL) intravascular metabolism is complex, and the major HDL functions are esterification of cholesterol and reverse cholesterol transport, in which cholesterol from cells is excreted in bile. HDL has also several other antiatherogenic functions: antioxidative, vasodilatatory, anti-inflammatory, antiapoptotic, antithrombotic, and anti-infectious. Low HDL cholesterol is a major risk factor for cardiovascular disease (CVD) and high HDL cholesterol may favor the many protective abilities of HDL. However, aspects of HDL function can be independent of HDL cholesterol levels, including the efflux of cholesterol from cells to HDL. Some populations show low incidence of CVD despite their low HDL cholesterol. Lipid exchange between HDL and other lipoproteins and cells is fundamental in HDL metabolism and reverse cholesterol transport. By determining HDL composition, lipid transfers can also affect HDL functions that depend on proteins that anchor on HDL particle surface. Cholesteryl ester protein (CETP) and phospholipid transfer protein facilitate lipid transfers among lipoprotein classes, but the role of the lipid transfers and transfer proteins in atherosclerosis and other diseases is not well established. CETP has become a therapeutic target because CETP inhibitors increase HDL cholesterol, but to date the clinical trials failed to show benefits for the patients. Recently, we introduced a practical in vitro assay to evaluate the simultaneous transfer from a donor nanoemulsion to HDL of unesterified and esterified cholesterol, phospholipids, and triglycerides. Groups of subjects at different clinical, nutritional, and training conditions were tested, and among other findings, lower transfer ratios of unesterified cholesterol to HDL were predictors of the presence of CVD.
- Clinical experience with drug delivery systems as tools to decrease the toxicity of anticancer chemotherapeutic agents(2017) MARANHAO, Raul C.; VITAL, Carolina G.; TAVONI, Thauany M.; GRAZIANI, Silvia R.Introduction: The toxicity of chemotherapeutic agents, resulting from their low pharmacological index, introduces considerable discomfort and risk to cancer patients. Among several strategies to reduce the toxicity of chemotherapeutic agents, targeted drug delivery is the most promising one. Areas covered: Liposomes, micelles, albumin-based, polymeric, dendritic and lipid core nanoparticles have been used as carriers to concentrate anticancer drugs in neoplastic tissues, and clinical studies of those preparations are reviewed. In most clinical studies, drug delivery systems reduced drug toxicity. Lipid core nanoparticles (LDE) that bind to cell lipoprotein receptors have the ability to concentrate in neoplastic tissues and were the first artificial non-liposomal system shown in in vivo studies to possess targeting properties. The toxicity reduction achieved by LDE as vehicle of carmustine, etoposide and paclitaxel was singularly strong. Expert opinion: The reduced toxicity offered by drug delivery systems has expanded treatment population that may benefit from chemotherapy including feeble, overtreated and elderly patients that would otherwise be offered palliative therapy. Drug delivery systems may either prolong the duration of treatments or allow increases in drug dose.
- Could statins constitute a novel treatment for endometriosis? Systematic review of the literature(2014) GIBRAN, Luciano; MARANHAO, Raul C.; ABRAO, Mauricio S.; BARACAT, Edmundo C.; PODGAEC, SergioEndometriosis, defined as the presence of endometrial glands and/or stroma outside the uterine cavity, is an estrogen-dependent disease that affects about 10% of reproductive age women. Theories to explain the etiology of endometriosis abound. These include the alteration of epithelial cells on peritoneal surface, metaplasia of embryonic remnants of the mullerian ducts, immune system abnormalities, and the dissemination of endometrial cells through the circulation or lymphatic system, as well as retrograde menstruation, the hypothesis currently favored for the development of endometriosis. Angiogenesis, the development of new capillaries from pre-existing blood vessels, has been proposed as a key mechanism in the pathogenesis of endometriosis. Again from an etiological perspective, the formation of endometriotic implants requires ectopic fixation and proliferation of endometrial stroma and glands. The process of invasive insertion of endometriotic tissues involves the degradation of the extracellular matrix, and altered expression of matrix metalloproteinases (MMPs) in the eutopic and ectopic endometrium. Considering the antiproliferative, antiangiogenic, antioxidant, anti-inflammatory properties and matrix metalloproteinase activity inhibition of statins and the original studies addressing the possible mechanisms of action in endometriosis, the aim of this systematic review was to synthesize the research conducted to date in order to propose statins as possible and effective tools for controlling this disease.