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1.
Adv Exp Med Biol ; 1182: 181-199, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31777019

RESUMO

Cardiovascular diseases (CVDs) are disorders of the heart and blood vessels and include coronary heart diseases, cerebrovascular diseases, rheumatic heart diseases, and other conditions. CVDs are one of the most major causes of morbidity and mortality around the world, taking the lives of 17.9 million people every year. Several investigations have shown the influence of Ganoderma lucidum (G. lucidum, Lingzhi) on some metabolic markers, such as low-density lipoprotein (LDL), high-density lipoprotein (HDL), total cholesterol (TC), blood pressure, and oxidative damage. G. lucidum potentially reduces the risk of suffering cardiovascular diseases. Some studies found that G. lucidum prevented from heart damage in a variety of disease models, such as streptozotocin (STZ)-induced diabetic, high-fat-diet-induced diabetic, isoprenaline (ISO)-induced myocardial hypertrophy, acute ethanol-induced heart toxicity, and transverse aortic constriction (TAC) models. This chapter summarizes putative preventive and therapeutic effects of G. lucidum on cardiovascular diseases and the potential clinical use of G. lucidum involved in these effects.


Assuntos
Produtos Biológicos/farmacologia , Doenças Cardiovasculares/tratamento farmacológico , Sistema Cardiovascular/efeitos dos fármacos , Reishi/química , Humanos
4.
J Clin Pathol ; 72(12): 785-799, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31611285

RESUMO

Progresses in liquid-based assays may provide novel useful non-invasive indicators of cardiovascular (CV) diseases. By analysing circulating cells or their products in blood, saliva and urine samples, we can investigate molecular changes present at specific time points in each patient allowing sequential monitoring of disease evolution. For example, an increased number of circulating endothelial cells may be a diagnostic biomarker for diabetic nephropathy and heart failure with preserved ejection fraction. The assessment of circulating cell-free DNA (cfDNA) levels may be useful to predict severity of acute myocardial infarction, as well as diagnose heart graft rejection. Remarkably, circulating epigenetic biomarkers, including DNA methylation, histone modifications and non-coding RNAs are key pathogenic determinants of CV diseases representing putative useful biomarkers and drug targets. For example, the unmethylated FAM101A gene may specifically trace cfDNA derived from cardiomyocyte death providing a powerful diagnostic biomarker of apoptosis during ischaemia. Moreover, changes in plasma levels of circulating miR-92 may predict acute coronary syndrome onset in patients with diabetes. Now, network medicine provides a framework to analyse a huge amount of big data by describing a CV disease as a result of a chain of molecular perturbations rather than a single defect (reductionism). We outline advantages and challenges of liquid biopsy with respect to traditional tissue biopsy and summarise the main completed and ongoing clinical trials in CV diseases. Furthermore, we discuss the importance of combining fluid-based assays, big data and network medicine to improve precision medicine and personalised therapy in this field.


Assuntos
Líquidos Corporais/metabolismo , Doenças Cardiovasculares/diagnóstico , Técnicas de Diagnóstico Molecular , Medicina de Precisão , Biomarcadores/metabolismo , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/metabolismo , Ácidos Nucleicos Livres/sangue , Tomada de Decisão Clínica , Humanos , Biópsia Líquida , Seleção de Pacientes , Valor Preditivo dos Testes , Prognóstico , Reprodutibilidade dos Testes
5.
An Acad Bras Cienc ; 91(3): e20180424, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31553364

RESUMO

Abstract: Cardiovascular diseases (CVDs) are leading causes of death in the world, owing to noticeable incidence and mortality. Traditional Chinese Medicine (TCM) SINI Decoction (SND) is used to prevent and treat CVDs, which has attracted extensive attention for its moderate and little side effects. However, the involved molecular mechanisms are exceedingly complicated and remain unclear. Systems pharmacology, as a novel approach that integrates systems biology and pharmacology plays a significant role in investigating the molecular mechanism of TCM. In systems pharmacology approach, we use to systematically uncover the mechanisms of action in Chinese medicinal formula SND as an effective treatment for CVDs, which mainly includes:1) molecular database building; 2) ADME evaluation; 3) target-fishing 4) network construction and analysis. The results show that 78 underlying valid ingredients and their corresponding 71 direct targets of SND were obtained. And SND take part in cardiomyocyte protection, blood pressure regulation, and lipid regulation module in treatment of CVDs by cooperative way. Systems pharmacology as an emerging field that investigates the molecular mechanisms of TCM through pharmacokinetic evaluation target prediction, and pathway analysis, which will facilitate the development of traditional Chinese herbs in modern medicine.


Assuntos
Doenças Cardiovasculares/tratamento farmacológico , Medicamentos de Ervas Chinesas/química , Medicina Tradicional Chinesa , Biologia de Sistemas/métodos , Humanos , Modelos Biológicos
6.
Adv Exp Med Biol ; 1178: 103-112, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31493224

RESUMO

Coenzyme Q10 (CoQ10) is a vitamin-like substance which functions as an electron carrier within the mitochondrial respiratory chain, as well as serving as an important intracellular antioxidant. Most of the body's CoQ10 requirements are met by endogenous synthesis, although the capacity for CoQ10 production decreases substantially with increasing age. In this article we have reviewed the potential role of CoQ10 supplementation in the treatment of tissue fibrosis, which has been implicated in the age-related loss of function of various organs including the heart. Clinical studies have indicated that CoQ10 supplementation may decrease the level of cardiovascular fibrosis to which older individuals are subjected, and thereby improve cardiovascular function and reduce the risk of cardiovascular associated mortality. Although the factors responsible for the anti-fibrotic action of CoQ10 have yet to be fully elucidated, its antioxidant and anti-inflammatory functions are thought to be major contributors to its clinical efficacy in the treatment of this age-related disorder.


Assuntos
Antioxidantes , Ubiquinona/análogos & derivados , Antioxidantes/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/patologia , Fibrose/tratamento farmacológico , Humanos , Ubiquinona/uso terapêutico
7.
Medicine (Baltimore) ; 98(37): e17095, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31517834

RESUMO

BACKGROUND: The effectiveness of folic acid supplementation in stroke risk has been investigated, however, the available results are inconclusive and conflicting. The purpose of this systemic review and meta-analysis was to assess the effect of folic acid in patients with cardiovascular disease (CVD). METHODS: By searching the PubMed, EMBASE, and Cochrane library databases, we conducted a meta-analysis to evaluate effect of folic acid supplementation in patients with CVD. All-cause mortality, cardiovascular mortality, the risk of coronary heart disease (CHD) and stroke were summarized; hazard ratios (HR), the relative risk (RR) and its 95% confidence interval (CI) were also calculated. Fixed effects models were used to combine the data. A total of 12 randomized controlled trials, which involved 47,523 participants, met the inclusion criteria in this systematic review and meta-analysis. RESULTS: Our meta-analysis showed that cardiovascular patients who received folic acid therapy had significantly decreased risk of stroke (RR = 0.85, 95% CI = 0.77-0.94, Pheterogeneity = .347, I = 10.6%) compared with patients who received control treatment. However, no significant difference in all-cause mortality (HR, 0.97, 95% CI, 0.86-1.10, Pheterogeneity = .315, I = 15.4%), cardiovascular mortality (HR, 0.87, 95% CI, 0.66-1.15, Pheterogeneity = .567, I = 0) and risk of CHD (RR, 1.04, 95% CI, 0.99-1.10, Pheterogeneity = .725, I = 0) were found between the 2 groups. CONCLUSION: This meta-analysis suggested that folic acid supplementation significantly reduced the risk of stroke in patients with CVD.


Assuntos
Doenças Cardiovasculares/tratamento farmacológico , Ácido Fólico/farmacologia , Doenças Cardiovasculares/mortalidade , Suplementos Nutricionais , Ácido Fólico/uso terapêutico , Humanos , Complexo Vitamínico B/farmacologia , Complexo Vitamínico B/uso terapêutico
9.
Curr Top Med Chem ; 19(20): 1790-1817, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31400268

RESUMO

BACKGROUND: Cardiovascular diseases remain the leading cause of morbidity and mortality in the world, with elevated Low-Density Lipoprotein-Cholesterol (LDL-C) levels as the major risk factor. Lower levels of LDL-C can effectively reduce the risk of cardiovascular diseases. Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays an important role in regulating the degradation of hepatic LDL receptors that remove LDL-C from the circulation. PCSK9 inhibitors are a new class of agents that are becoming increasingly important in the treatment to reduce LDL-C levels. Two PCSK9 inhibitors, alirocumab and evolocumab, have been approved to treat hypercholesterolemia and are available in the United States and the European Union. Through the inhibition of PCSK9 and increased recycling of LDL receptors, serum LDL-C levels can be significantly reduced. OBJECTIVE: This review will describe the chemistry, pharmacokinetics, and pharmacodynamics of PCSK9 inhibitors and their clinical effects.


Assuntos
Doenças Cardiovasculares/tratamento farmacológico , Pró-Proteína Convertase 9/antagonistas & inibidores , Inibidores de Serino Proteinase/farmacologia , Animais , Doenças Cardiovasculares/metabolismo , Humanos , Pró-Proteína Convertase 9/metabolismo
10.
Curr Top Med Chem ; 19(21): 1918-1947, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31393249

RESUMO

microRNAs (miRNAs) are an evolutionarily conserved class of small single-stranded noncoding RNAs. The aberrant expression of specific miRNAs has been implicated in the development and progression of diverse cardiovascular diseases. For many decades, miRNA therapeutics has flourished, taking advantage of the fact that miRNAs can modulate gene expression and control cellular phenotypes at the posttranscriptional level. Genetic replacement or knockdown of target miRNAs by chemical molecules, referred to as miRNA mimics or inhibitors, has been used to reverse their abnormal expression as well as their adverse biological effects in vitro and in vivo in an effort to fully implement the therapeutic potential of miRNA-targeting treatment. However, the limitations of the chemical structure and delivery systems are hindering progress towards clinical translation. Here, we focus on the regulatory mechanisms and therapeutic trials of several representative miRNAs in the context of specific cardiovascular diseases; from this basic perspective, we evaluate chemical modifications and delivery vectors of miRNA-based chemical molecules and consider the underlying challenges of miRNA therapeutics as well as the clinical perspectives on their applications.


Assuntos
Fármacos Cardiovasculares/farmacologia , Doenças Cardiovasculares/tratamento farmacológico , MicroRNAs/antagonistas & inibidores , Bibliotecas de Moléculas Pequenas/farmacologia , Animais , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/metabolismo , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Bibliotecas de Moléculas Pequenas/química
11.
Curr Top Med Chem ; 19(20): 1818-1849, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31456521

RESUMO

Type 2 diabetes mellitus is one of the most common forms of the disease worldwide. Hyperglycemia and insulin resistance play key roles in type 2 diabetes mellitus. Renal glucose reabsorption is an essential feature in glycaemic control. Kidneys filter 160 g of glucose daily in healthy subjects under euglycaemic conditions. The expanding epidemic of diabetes leads to a prevalence of diabetes-related cardiovascular disorders, in particular, heart failure and renal dysfunction. Cellular glucose uptake is a fundamental process for homeostasis, growth, and metabolism. In humans, three families of glucose transporters have been identified, including the glucose facilitators GLUTs, the sodium-glucose cotransporter SGLTs, and the recently identified SWEETs. Structures of the major isoforms of all three families were studied. Sodium-glucose cotransporter (SGLT2) provides most of the capacity for renal glucose reabsorption in the early proximal tubule. A number of cardiovascular outcome trials in patients with type 2 diabetes have been studied with SGLT2 inhibitors reducing cardiovascular morbidity and mortality. The current review article summarises these aspects and discusses possible mechanisms with SGLT2 inhibitors in protecting heart failure and renal dysfunction in diabetic patients. Through glucosuria, SGLT2 inhibitors reduce body weight and body fat, and shift substrate utilisation from carbohydrates to lipids and, possibly, ketone bodies. These pleiotropic effects of SGLT2 inhibitors are likely to have contributed to the results of the EMPA-REG OUTCOME trial in which the SGLT2 inhibitor, empagliflozin, slowed down the progression of chronic kidney disease and reduced major adverse cardiovascular events in high-risk individuals with type 2 diabetes. This review discusses the role of SGLT2 in the physiology and pathophysiology of renal glucose reabsorption and outlines the unexpected logic of inhibiting SGLT2 in the diabetic kidney.


Assuntos
Doenças Cardiovasculares/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/farmacologia , Nefropatias/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Transportador 2 de Glucose-Sódio/metabolismo , Doenças Cardiovasculares/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Humanos , Nefropatias/metabolismo
12.
Rev Med Suisse ; 15(659): 1454-1457, 2019 Aug 21.
Artigo em Francês | MEDLINE | ID: mdl-31436061

RESUMO

Statins are the most commonly prescribed cholesterol-lowering drugs for cardiovascular prevention. Data from randomized clinical trials have shown an increased risk of diabetes mellitus type 2 (DT2) on statin treatment. These findings have been confirmed in genetic Mendelian randomization studies and in observational cohorts. The molecular mechanisms remain partly unknown. The risk of TD2 is higher with high doses of statins and in people with preexisting risk factors for T2D (prediabetes, metabolic syndrome). The cardiovascular benefit of statins overdrive by far the risk of diabetes and the prescription of statins in high risk cardiovascular subjects should not be questioned. Glycaemic monitoring and the adaptation of lifestyle and dietary measures are recommended for subjects at risk of T2D.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Inibidores de Hidroximetilglutaril-CoA Redutases , Doenças Cardiovasculares/tratamento farmacológico , Diabetes Mellitus Tipo 2/induzido quimicamente , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de Risco
13.
Stud Health Technol Inform ; 264: 1712-1713, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31438306

RESUMO

We developed a HeartGuardian app and explored its effects supporting people with CVD on lipid control and medication adherence. Fifty-seven patients were enrolled, 29 in the intervention group and 28 in the control group. The 12-week intervention resulted in a moderate improvement in lipid level and greater improvement in medication adherence (82.14% vs 37.93%, P = 0.001). These outcomes translate into significant differences in occurrence of major adverse cardiac events (28.75% vs 72.43%, P = 0.001).


Assuntos
Doenças Cardiovasculares , Prevenção Secundária , Smartphone , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/prevenção & controle , Humanos , Adesão à Medicação
14.
Eur J Med Chem ; 179: 272-309, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31255927

RESUMO

Inflammation is a biological function which triggered after the mechanical tissue disruption or from the responses by the incidence of physical, chemical or biological negotiator in body. These responses are essential act provided by the immune system during infection and tissue injury to maintain normal tissue homeostasis. Inflammation is a quite complicated process at molecular level with the involvement of several proinflammatory expressions. Several health problems are associated with prolonged inflammation, which effects nearly all major to minor diseases. The molecular and epidemiological studies jagged that the inflammation is closely associated with several disorders with their specific targets. It would be great achievement for human health around the world to overcome on inflammation. Mostly used anti-inflammatory drugs are at high risk of side effects and also expensive. Hence, the plant-based formulations gained a wide acceptance by the public and medical experts to treat it. Due to extensive dispersal, chemical diversity and systematically established biological potentials of natural products have induced renewed awareness as a gifted source for medications. However, today's urgent need to search for cheaper, more potent and safe anti-inflammatory medications to overcome on current situation. The goal of this review to compile an update on inflammation, associated diseases, molecular targets, inflammatory mediators and role of natural products. The entire text concise the involvement of various cytokines in pathogenesis of various human disorders. This assignment discussed about 321 natural products with their promising anti-inflammatory potential discovered during January 2009 to December 2018 with 262 citations.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Produtos Biológicos/uso terapêutico , Inflamação/tratamento farmacológico , Neoplasias/tratamento farmacológico , Anti-Inflamatórios não Esteroides/química , Artrite Reumatoide/tratamento farmacológico , Produtos Biológicos/química , Doenças Cardiovasculares/tratamento farmacológico , Humanos , Inflamação/metabolismo , Dermatopatias/tratamento farmacológico
15.
Food Chem ; 299: 125124, 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31288163

RESUMO

Inflammation plays a key role in diseases such as diabetes, asthma, cardiovascular diseases and cancer. Diet can influence different stages of inflammation and can have an important impact on several inflammatory diseases. Increasing scientific evidence has shown that polyphenolic compounds, such as flavonoids, which are found in fruits, vegetables, legumes, or cocoa, can have anti-inflammatory properties. Recent studies have demonstrated that flavonoids can inhibit regulatory enzymes or transcription factors important for controlling mediators involved in inflammation. Flavonoids are also known as potent antioxidants with the potential to attenuate tissue damage or fibrosis. Consequently, numerous studies in vitro and in animal models have found that flavonoids have the potential to inhibit the onset and development of inflammatory diseases. In the present review, we focused in flavonoids, the most abundant polyphenols in the diet, to give an overview of the most recent scientific knowledge about their impact on different inflammatory diseases.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Doenças Cardiovasculares/tratamento farmacológico , Flavonoides/farmacologia , Inflamação/tratamento farmacológico , Neoplasias/tratamento farmacológico , Animais , Anti-Inflamatórios/análise , Antioxidantes/análise , Cacau/química , Doenças Cardiovasculares/patologia , Dieta , Fabaceae/química , Flavonoides/análise , Frutas/química , Humanos , Neoplasias/patologia , Polifenóis/análise , Polifenóis/farmacologia , Verduras/química
16.
Int Heart J ; 60(4): 910-918, 2019 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-31308328

RESUMO

Previous studies have provided established evidence on adverse outcomes of the coadministration of proton pump inhibitors (PPIs) and clopidogrel, whereas cerebro-cardiovascular outcomes of PPI use in the absence of clopidogrel therapy remain controversial.In this study, we aimed to assess the association between PPIs and cerebro-cardiovascular outcomes independent of clopidogrel.Systematic searches were conducted in the Cochrane Library, PubMed, and Embase databases for all relevant studies up to August 2018. Odds ratios (ORs) with its 95% confidence intervals (CIs) were abstracted and pooled using the random-effects model.A total of 14 observational studies (13 cohort studies and 1 case-control study) were identified. Compared with non-PPI users, PPI users experienced higher risks of stroke (OR: 1.22, 95% CI: 1.08-1.36), myocardial infarction (MI; OR: 1.23, 95% CI: 1.14-1.32), cardiovascular death (OR: 1.83, 95% CI: 1.69-1.98), and major adverse cardiovascular events (MACEs; OR: 1.22, 95% CI: 1.05-1.40) independent of clopidogrel use, but not all-cause death (OR: 1.50, 95% CI: 0.99-2.25). In the subgroup analysis, PPI alone was associated with significant risks of new-onset MI (OR: 1.23, 95% CI: 1.13-1.35) and stroke (OR: 1.17, 95% CI: 1.05-1.30) in patients without previous MI or stoke and recurrent MI (OR: 1.24, 95% CI: 1.02-1.51) and stroke (OR: 1.36, 95% CI: 1.19-1.55) risks in patients with a previous MI.Based on current publications, PPI use seems to be associated with increased risks of stroke, MI, cardiovascular death, and MACEs independent of clopidogrel. Greater caution should be therefore exercised while considering its clinical benefits and further investigate any causal relationships.


Assuntos
Doenças Cardiovasculares/tratamento farmacológico , Transtornos Cerebrovasculares/tratamento farmacológico , Clopidogrel/farmacologia , Inibidores da Bomba de Prótons/farmacologia , Doenças Cardiovasculares/mortalidade , Causas de Morte/tendências , Transtornos Cerebrovasculares/mortalidade , Saúde Global , Humanos , Estudos Observacionais como Assunto , Inibidores da Agregação de Plaquetas/farmacologia , Fatores de Risco , Taxa de Sobrevida/tendências
17.
Inflammopharmacology ; 27(5): 863-869, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31309484

RESUMO

The failure of mechanisms of natural anti-coagulation either due to genetic impairment or due to severe external injuries may result in a condition called thrombosis. This is believed to be the primary cause for a variety of life-threatening conditions such as: heart attack, stroke, pulmonary embolism, thrombophlebitis, and deep venous thrombosis (DVT). The growing number of these incidents requires an alternative anti-coagulant or anti-thrombotic agent that has minimal side effects and improved efficiency. For decades, plant polyphenols, especially flavonoids, were known for their vital role in preventing various diseases such as cancer. Mitigating excessive oxidative stress caused by reactive oxygen species (ROS) with anti-oxidant-rich flavonoids may reduce the risk of hyper-activation of platelets, cardiovascular diseases (CVD), pain, and thrombosis. Furthermore, flavonoids may mitigate endothelial dysfunction (ED), which generally correlates to the development of coronary artery and vascular diseases. Flavonoids also reduce the risk of atherosclerosis and atherothrombotic disease by inhibiting excessive tissue factor (TF) availability in the endothelium. Although the role of flavonoids in CVD is widely discussed, to the best of our knowledge, their role as anti-thrombotic lead has not been discussed. This review aims to focus on the biological uses of dietary flavonoids and their role in the treatment of various coagulation disorders, and may provide some potential lead to the drug discovery process in this area.


Assuntos
Doenças Cardiovasculares/tratamento farmacológico , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Inflamação/tratamento farmacológico , Trombose/tratamento farmacológico , Animais , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Doenças Cardiovasculares/metabolismo , Humanos , Inflamação/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Trombose/metabolismo
18.
Protein Pept Lett ; 26(9): 664-675, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31215368

RESUMO

Bioactive peptides are short chain of amino acids (usually 2-20) that are linked by amide bond in a specific sequence which have some biological effects in animals or humans. These can be of diverse origin like plant, animal, fish, microbe, marine organism or even synthetic. They are successfully used in the management of many diseases. In recent years increased attention has been raised for its effects and mechanism of action in various disease conditions like cancer, immunity, cardiovascular disease, hypertension, inflammation, diabetes, microbial infections etc. Bioactive peptides are more bioavailable and less allergenic when compared to total proteins. Food derived bioactive peptides have health benefits and its demand has increased tremendously over the past decade. This review gives a view on last two years research on potential bioactive peptides derived from food which have significant therapeutic effects.


Assuntos
Produtos Biológicos/uso terapêutico , Alimentos , Peptídeos/uso terapêutico , Animais , Produtos Biológicos/química , Produtos Biológicos/metabolismo , Doenças Cardiovasculares/tratamento farmacológico , Diabetes Mellitus/tratamento farmacológico , Humanos , Hipertensão/tratamento farmacológico , Doenças do Sistema Imunitário/tratamento farmacológico , Inflamação/tratamento farmacológico , Neoplasias/tratamento farmacológico , Peptídeos/química , Peptídeos/metabolismo
20.
Expert Opin Ther Pat ; 29(7): 555-578, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31204543

RESUMO

INTRODUCTION: Human neutrophil elastase (HNE) is involved in a variety of serious chronic diseases, especially cardiopulmonary pathologies. For this reason, the regulation of HNE activity represents a promising therapeutic approach, which is evident by the development of a number of new and selective HNE inhibitors, both in the academic and pharmaceutical environments. AREAS COVERED: The present review analyzes and summarizes the patent literature regarding human neutrophil elastase inhibitors for the treatment of cardiopulmonary diseases over 2014-2018. EXPERT OPINION: HNE is an interesting and defined target to treat various inflammatory diseases, including a number of cardiopulmonary pathologies. The research in this field is quite active, and a number of HNE inhibitors are currently in various stages of clinical development. In addition, new opportunities for HNE inhibitor development stem from recent studies demonstrating the involvement of HNE in many other inflammatory pathologies, including rheumatoid arthritis, inflammatory bowel disease, skin diseases, and cancer. Furthermore, the development of dual HNE/proteinase 3 inhibitors is being pursued as an innovative approach for the treatment of neutrophilic inflammatory diseases. Thus, these new developments will likely stimulate new and increased interest in this important therapeutic target and for the development of novel and selective HNE inhibitors.


Assuntos
Desenvolvimento de Medicamentos/métodos , Elastase de Leucócito/efeitos dos fármacos , Proteínas Secretadas Inibidoras de Proteinases/farmacologia , Animais , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/enzimologia , Doenças Cardiovasculares/fisiopatologia , Humanos , Inflamação/tratamento farmacológico , Inflamação/fisiopatologia , Elastase de Leucócito/metabolismo , Pneumopatias/tratamento farmacológico , Pneumopatias/enzimologia , Pneumopatias/fisiopatologia , Patentes como Assunto
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