Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.018
Filtrar
1.
Drug Discov Ther ; 14(5): 256-258, 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33116037

RESUMO

In the ongoing coronavirus diseases-2019 (COVID-19) crisis that caused immense suffering and deaths, the choice of therapy for the prevention and life-saving conditions must be based on sound scientific evidence. Uncertainty and apprehension are exacerbated in people using angiotensin-converting enzyme (ACE) inhibitors to control their comorbidities such as hypertension and diabetes. These drugs are reported to result in unfavorable outcome as they tend to increase the levels of ACE2 which mediates the entry of SARS-CoV-2. Amiloride, a prototypic inhibitor of epithelial sodium channels (ENaC) can be an ideal candidate for COVID-19 patients, given its ACE reducing and cytosolic pH increasing effects. Moreover, its potassium-sparing and anti-epileptic activities make it a promising alternative or a combinatorial agent.


Assuntos
Amilorida/farmacologia , Antivirais/farmacologia , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Bloqueadores do Canal de Sódio Epitelial/farmacologia , Pneumonia Viral/tratamento farmacológico , Mucosa Respiratória/efeitos dos fármacos , Internalização do Vírus/efeitos dos fármacos , Células A549 , Betacoronavirus/patogenicidade , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/enzimologia , Infecções por Coronavirus/enzimologia , Infecções por Coronavirus/virologia , Regulação para Baixo , Interações Hospedeiro-Patógeno , Humanos , Pandemias , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/enzimologia , Pneumonia Viral/virologia , Receptores Virais/metabolismo , Mucosa Respiratória/enzimologia , Mucosa Respiratória/virologia
2.
Cardiovasc Toxicol ; 20(5): 443-447, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32729064

RESUMO

Coronavirus disease 2019 (COVID-19) is declared as a pandemic that has spread worldwide, affecting 205 countries. The disease affected 1, 40, 43, 176 individuals and caused 5, 97, 583 deaths around the globe. The organism responsible for the cause of disease is Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). SARS-CoV-2 enters into the cell via receptors present on the cell surface named angiotensin-converting enzyme 2 (ACE2) receptor. Notwithstanding ACE2 receptors acts as a gateway for infection, and most of the cardiovascular patients are treated with the ACE inhibitors. Thus, the role of ACE inhibitors or angiotensin receptor blockers may play a critical role in the severity or outcome of disease. Also, the effect of ACE inhibitors varies with the polymorphism in ACE2 receptors present in the individuals. Hence, it is the need of the hour to investigate the mechanisms which could better aid in the treatment of COVID-19-infected cardiovascular disease (CVD) patients.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Betacoronavirus/patogenicidade , Fármacos Cardiovasculares/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Infecções por Coronavirus/virologia , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/virologia , Internalização do Vírus/efeitos dos fármacos , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Fármacos Cardiovasculares/efeitos adversos , Doenças Cardiovasculares/enzimologia , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/fisiopatologia , Infecções por Coronavirus/enzimologia , Infecções por Coronavirus/mortalidade , Interações entre Hospedeiro e Microrganismos , Humanos , Pandemias , Segurança do Paciente , Peptidil Dipeptidase A/genética , Variantes Farmacogenômicos , Pneumonia Viral/enzimologia , Pneumonia Viral/mortalidade , Polimorfismo Genético , Prognóstico , Medição de Risco , Fatores de Risco
3.
Arq Bras Cardiol ; 114(5): 817-822, 2020 06 01.
Artigo em Inglês, Português | MEDLINE | ID: covidwho-532431

RESUMO

Coronavirus disease 2019 (COVID-19) is a global pandemic affecting the world, seen in more than 1,300,000 patients. COVID-19 acts through the angiotensin-converting enzyme 2 (ACE2) receptor. Cardiovascular comorbidities are more common with COVID-19, and nearly 10% of cases develop myocarditis (22% of critical patients). Further research is needed to continue or discontinue ACE inhibitors and angiotensin receptor blockers, which are essential in hypertension and heart failure in COVID-19. Intensive research is promising for the treatment and prevention of COVID-19.


Assuntos
Betacoronavirus , Doenças Cardiovasculares/epidemiologia , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Antagonistas de Receptores de Angiotensina/metabolismo , Animais , Antirreumáticos/uso terapêutico , Antivirais/uso terapêutico , Doenças Cardiovasculares/enzimologia , Doenças Cardiovasculares/mortalidade , China/epidemiologia , Cloroquina/uso terapêutico , Comorbidade , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/enzimologia , Infecções por Coronavirus/mortalidade , Humanos , Hipertensão/enzimologia , Hipertensão/epidemiologia , Pandemias , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/enzimologia , Pneumonia Viral/mortalidade
4.
Arq Bras Cardiol ; 114(5): 817-822, 2020 06 01.
Artigo em Inglês, Português | MEDLINE | ID: mdl-32491073

RESUMO

Coronavirus disease 2019 (COVID-19) is a global pandemic affecting the world, seen in more than 1,300,000 patients. COVID-19 acts through the angiotensin-converting enzyme 2 (ACE2) receptor. Cardiovascular comorbidities are more common with COVID-19, and nearly 10% of cases develop myocarditis (22% of critical patients). Further research is needed to continue or discontinue ACE inhibitors and angiotensin receptor blockers, which are essential in hypertension and heart failure in COVID-19. Intensive research is promising for the treatment and prevention of COVID-19.


Assuntos
Betacoronavirus , Doenças Cardiovasculares/epidemiologia , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Antagonistas de Receptores de Angiotensina/metabolismo , Animais , Antirreumáticos/uso terapêutico , Antivirais/uso terapêutico , Doenças Cardiovasculares/enzimologia , Doenças Cardiovasculares/mortalidade , China/epidemiologia , Cloroquina/uso terapêutico , Comorbidade , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/enzimologia , Infecções por Coronavirus/mortalidade , Humanos , Hipertensão/enzimologia , Hipertensão/epidemiologia , Pandemias , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/enzimologia , Pneumonia Viral/mortalidade
5.
Life Sci ; 255: 117821, 2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-32445759

RESUMO

Human sepsis is the result of a multifaceted pathological process causing marked dysregulation of cardiovascular responses. A more sophisticated understanding of the pathogenesis of sepsis is certainly prerequisite. Evidence from studies provide further insight into the role of inducible nitric oxide synthase (iNOS) isoform. Results on inhibition of iNOS in sepsis models remain inconclusive. Concern has been devoted to improving our knowledge and understanding of the role of iNOS. The aim of this review is to define the role of iNOS in redox homeostasis disturbance, the detailed mechanisms linking iNOS and posttranslational modifications (PTMs) to cardiovascular dysfunctions, and their future implications in sepsis settings. Many questions related to the iNOS and PTMs still remain open, and much more work is needed on this.


Assuntos
Doenças Cardiovasculares/etiologia , Óxido Nítrico Sintase Tipo II/metabolismo , Sepse/complicações , Animais , Doenças Cardiovasculares/enzimologia , Humanos , Oxirredução , Processamento de Proteína Pós-Traducional , Sepse/enzimologia , Sepse/fisiopatologia
7.
Am J Physiol Heart Circ Physiol ; 318(5): H1084-H1090, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: covidwho-23170

RESUMO

The novel SARS coronavirus SARS-CoV-2 pandemic may be particularly deleterious to patients with underlying cardiovascular disease (CVD). The mechanism for SARS-CoV-2 infection is the requisite binding of the virus to the membrane-bound form of angiotensin-converting enzyme 2 (ACE2) and internalization of the complex by the host cell. Recognition that ACE2 is the coreceptor for the coronavirus has prompted new therapeutic approaches to block the enzyme or reduce its expression to prevent the cellular entry and SARS-CoV-2 infection in tissues that express ACE2 including lung, heart, kidney, brain, and gut. ACE2, however, is a key enzymatic component of the renin-angiotensin-aldosterone system (RAAS); ACE2 degrades ANG II, a peptide with multiple actions that promote CVD, and generates Ang-(1-7), which antagonizes the effects of ANG II. Moreover, experimental evidence suggests that RAAS blockade by ACE inhibitors, ANG II type 1 receptor antagonists, and mineralocorticoid antagonists, as well as statins, enhance ACE2 which, in part, contributes to the benefit of these regimens. In lieu of the fact that many older patients with hypertension or other CVDs are routinely treated with RAAS blockers and statins, new clinical concerns have developed regarding whether these patients are at greater risk for SARS-CoV-2 infection, whether RAAS and statin therapy should be discontinued, and the potential consequences of RAAS blockade to COVID-19-related pathologies such as acute and chronic respiratory disease. The current perspective critically examines the evidence for ACE2 regulation by RAAS blockade and statins, the cardiovascular benefits of ACE2, and whether ACE2 blockade is a viable approach to attenuate COVID-19.


Assuntos
Betacoronavirus/fisiologia , Doenças Cardiovasculares/enzimologia , Doenças Cardiovasculares/virologia , Infecções por Coronavirus/enzimologia , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/enzimologia , Animais , Betacoronavirus/metabolismo , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Humanos , Masculino , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Ratos , Ratos Endogâmicos Lew , Internalização do Vírus
10.
Am J Physiol Heart Circ Physiol ; 318(5): H1084-H1090, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32228252

RESUMO

The novel SARS coronavirus SARS-CoV-2 pandemic may be particularly deleterious to patients with underlying cardiovascular disease (CVD). The mechanism for SARS-CoV-2 infection is the requisite binding of the virus to the membrane-bound form of angiotensin-converting enzyme 2 (ACE2) and internalization of the complex by the host cell. Recognition that ACE2 is the coreceptor for the coronavirus has prompted new therapeutic approaches to block the enzyme or reduce its expression to prevent the cellular entry and SARS-CoV-2 infection in tissues that express ACE2 including lung, heart, kidney, brain, and gut. ACE2, however, is a key enzymatic component of the renin-angiotensin-aldosterone system (RAAS); ACE2 degrades ANG II, a peptide with multiple actions that promote CVD, and generates Ang-(1-7), which antagonizes the effects of ANG II. Moreover, experimental evidence suggests that RAAS blockade by ACE inhibitors, ANG II type 1 receptor antagonists, and mineralocorticoid antagonists, as well as statins, enhance ACE2 which, in part, contributes to the benefit of these regimens. In lieu of the fact that many older patients with hypertension or other CVDs are routinely treated with RAAS blockers and statins, new clinical concerns have developed regarding whether these patients are at greater risk for SARS-CoV-2 infection, whether RAAS and statin therapy should be discontinued, and the potential consequences of RAAS blockade to COVID-19-related pathologies such as acute and chronic respiratory disease. The current perspective critically examines the evidence for ACE2 regulation by RAAS blockade and statins, the cardiovascular benefits of ACE2, and whether ACE2 blockade is a viable approach to attenuate COVID-19.


Assuntos
Betacoronavirus/fisiologia , Doenças Cardiovasculares/enzimologia , Doenças Cardiovasculares/virologia , Infecções por Coronavirus/enzimologia , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/enzimologia , Animais , Betacoronavirus/metabolismo , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Humanos , Masculino , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Ratos , Ratos Endogâmicos Lew , Internalização do Vírus
11.
Cardiovasc Res ; 116(12): 1932-1936, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32267499

RESUMO

Angiotensin-converting enzyme 2 (ACE2) has emerged as a key regulator of the renin-angiotensin system in cardiovascular (CV) disease and plays a pivotal role in infections by coronaviruses and influenza viruses. The present review is primarily focused on the findings to indicate the role of ACE2 in the relationship of coronaviruses and influenza viruses to CV disease. It is postulated that the risk of coronavirus or influenza virus infection is high, at least partly due to high ACE2 expression in populations with a high CV risk. Coronavirus and influenza virus vaccine usage in high CV risk populations could be a potential strategy to prevent both CV disease and coronavirus/influenza virus infections.


Assuntos
Doenças Cardiovasculares/enzimologia , Infecções por Coronavirus/virologia , Coronavirus/metabolismo , Orthomyxoviridae/metabolismo , Peptidil Dipeptidase A/metabolismo , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Animais , Doenças Cardiovasculares/metabolismo , Humanos
12.
Circulation ; 141(20): 1648-1655, 2020 May 19.
Artigo em Inglês | MEDLINE | ID: covidwho-14032

RESUMO

Coronavirus disease 2019 (COVID-19) is a global pandemic affecting 185 countries and >3 000 000 patients worldwide as of April 28, 2020. COVID-19 is caused by severe acute respiratory syndrome coronavirus 2, which invades cells through the angiotensin-converting enzyme 2 receptor. Among patients with COVID-19, there is a high prevalence of cardiovascular disease, and >7% of patients experience myocardial injury from the infection (22% of critically ill patients). Although angiotensin-converting enzyme 2 serves as the portal for infection, the role of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers requires further investigation. COVID-19 poses a challenge for heart transplantation, affecting donor selection, immunosuppression, and posttransplant management. There are a number of promising therapies under active investigation to treat and prevent COVID-19.


Assuntos
Betacoronavirus , Doenças Cardiovasculares , Infecções por Coronavirus , Pandemias , Peptidil Dipeptidase A , Pneumonia Viral , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/enzimologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/enzimologia , Infecções por Coronavirus/terapia , Infecções por Coronavirus/virologia , Humanos , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/complicações , Pneumonia Viral/enzimologia , Pneumonia Viral/terapia , Pneumonia Viral/virologia , Receptores Virais/antagonistas & inibidores , Receptores Virais/metabolismo
13.
Circulation ; 141(20): 1648-1655, 2020 May 19.
Artigo em Inglês | MEDLINE | ID: covidwho-437727

RESUMO

Coronavirus disease 2019 (COVID-19) is a global pandemic affecting 185 countries and >3 000 000 patients worldwide as of April 28, 2020. COVID-19 is caused by severe acute respiratory syndrome coronavirus 2, which invades cells through the angiotensin-converting enzyme 2 receptor. Among patients with COVID-19, there is a high prevalence of cardiovascular disease, and >7% of patients experience myocardial injury from the infection (22% of critically ill patients). Although angiotensin-converting enzyme 2 serves as the portal for infection, the role of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers requires further investigation. COVID-19 poses a challenge for heart transplantation, affecting donor selection, immunosuppression, and posttransplant management. There are a number of promising therapies under active investigation to treat and prevent COVID-19.


Assuntos
Betacoronavirus , Doenças Cardiovasculares , Infecções por Coronavirus , Pandemias , Peptidil Dipeptidase A , Pneumonia Viral , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/enzimologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/enzimologia , Infecções por Coronavirus/terapia , Infecções por Coronavirus/virologia , Humanos , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/complicações , Pneumonia Viral/enzimologia , Pneumonia Viral/terapia , Pneumonia Viral/virologia , Receptores Virais/antagonistas & inibidores , Receptores Virais/metabolismo
14.
Int J Exp Pathol ; 101(1-2): 4-20, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32219922

RESUMO

A Disintegrin And Metalloproteinase with ThromboSpondin motif (ADAMTS)-5 was identified in 1999 as one of the enzymes responsible for cleaving aggrecan, the major proteoglycan in articular cartilage. Studies in vitro, ex vivo and in vivo have validated ADAMTS-5 as a target in osteoarthritis (OA), a disease characterized by extensive degradation of aggrecan. For this reason, it attracted the interest of many research groups aiming to develop a therapeutic treatment for OA patients. However, ADAMTS-5 proteoglycanase activity is not only involved in the dysregulated aggrecan proteolysis, which occurs in OA, but also in the physiological turnover of other related proteoglycans. In particular, versican, a major ADAMTS-5 substrate, plays an important structural role in heart and blood vessels and its proteolytic processing by ADAMTS-5 must be tightly regulated. On the occasion of the 20th anniversary of the discovery of ADAMTS-5, this review looks at the evidence for its detrimental role in OA, as well as its physiological turnover of cardiovascular proteoglycans. Moreover, the other potential functions of this enzyme are highlighted. Finally, challenges and emerging trends in ADAMTS-5 research are discussed.


Assuntos
Proteína ADAMTS5/metabolismo , Agrecanas/metabolismo , Doenças Cardiovasculares/enzimologia , Sistema Cardiovascular/enzimologia , Cartilagem Articular/enzimologia , Osteoartrite/enzimologia , Versicanas/metabolismo , Proteína ADAMTS5/antagonistas & inibidores , Animais , Doenças Cardiovasculares/patologia , Sistema Cardiovascular/patologia , Cartilagem Articular/patologia , Humanos , Osteoartrite/tratamento farmacológico , Osteoartrite/patologia , Inibidores de Proteases/uso terapêutico , Proteólise , Especificidade por Substrato , Remodelação Vascular
15.
Circulation ; 141(20): 1648-1655, 2020 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-32200663

RESUMO

Coronavirus disease 2019 (COVID-19) is a global pandemic affecting 185 countries and >3 000 000 patients worldwide as of April 28, 2020. COVID-19 is caused by severe acute respiratory syndrome coronavirus 2, which invades cells through the angiotensin-converting enzyme 2 receptor. Among patients with COVID-19, there is a high prevalence of cardiovascular disease, and >7% of patients experience myocardial injury from the infection (22% of critically ill patients). Although angiotensin-converting enzyme 2 serves as the portal for infection, the role of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers requires further investigation. COVID-19 poses a challenge for heart transplantation, affecting donor selection, immunosuppression, and posttransplant management. There are a number of promising therapies under active investigation to treat and prevent COVID-19.


Assuntos
Betacoronavirus , Doenças Cardiovasculares , Infecções por Coronavirus , Pandemias , Peptidil Dipeptidase A , Pneumonia Viral , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/enzimologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/enzimologia , Infecções por Coronavirus/terapia , Infecções por Coronavirus/virologia , Humanos , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/complicações , Pneumonia Viral/enzimologia , Pneumonia Viral/terapia , Pneumonia Viral/virologia , Receptores Virais/antagonistas & inibidores , Receptores Virais/metabolismo
16.
Biochim Biophys Acta Proteins Proteom ; 1868(4): 140360, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31926332

RESUMO

Cysteinyl cathepsins are lysosomal/endosomal proteases that mediate bulk protein degradation in these intracellular acidic compartments. Yet, studies indicate that these proteases also appear in the nucleus, nuclear membrane, cytosol, plasma membrane, and extracellular space. Patients with cardiovascular diseases (CVD) show increased levels of cathepsins in the heart, aorta, and plasma. Plasma cathepsins often serve as biomarkers or risk factors of CVD. In aortic diseases, such as atherosclerosis and abdominal aneurysms, cathepsins play pathogenic roles, but many of the same cathepsins are cardioprotective in hypertensive, hypertrophic, and infarcted hearts. During the development of CVD, cathepsins are regulated by inflammatory cytokines, growth factors, hypertensive stimuli, oxidative stress, and many others. Cathepsin activities in inflammatory molecule activation, immunity, cell migration, cholesterol metabolism, neovascularization, cell death, cell signaling, and tissue fibrosis all contribute to CVD and are reviewed in this article in memory of Dr. Nobuhiko Katunuma for his contribution to the field.


Assuntos
Doenças Cardiovasculares/enzimologia , Catepsinas/metabolismo , Animais , Aneurisma da Aorta Abdominal/enzimologia , Aterosclerose/enzimologia , Biomarcadores/metabolismo , Catepsinas/antagonistas & inibidores , Humanos , Camundongos , Fatores de Risco
17.
Nat Rev Cardiol ; 17(2): 96-115, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31350538

RESUMO

Lysine acetylation is a conserved, reversible, post-translational protein modification regulated by lysine acetyltransferases (KATs) and lysine deacetylases (KDACs; also known as histone deacetylases (HDACs)) that is involved in many cellular signalling pathways and diseases. Studies in animal models have revealed a regulatory role of reversible lysine acetylation in hypertension, vascular diseases, arrhythmia, heart failure and angiogenesis. Evidence from these studies indicates a therapeutic role of KDAC inhibitors (also known as HDAC inhibitors) in cardiovascular diseases. In this Review, we describe the diverse roles of KATs and KDACs in both the normal and the diseased heart. Among KDACs, class II and class III HDACs seem to have a protective role against both cardiac damage and vessel injury, whereas class I HDACs protect against vessel injury but have deleterious effects on the heart. These observations have important implications for the clinical utility of HDAC inhibitors as therapeutic agents for cardiovascular diseases. In addition, we summarize the latest data on nonacetylation acylations in the context of cardiovascular disease.


Assuntos
Fármacos Cardiovasculares/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Sistema Cardiovascular/efeitos dos fármacos , Inibidores de Histona Desacetilases/uso terapêutico , Histona Desacetilases/metabolismo , Lisina Acetiltransferases/antagonistas & inibidores , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Acetilação , Animais , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/enzimologia , Doenças Cardiovasculares/fisiopatologia , Sistema Cardiovascular/enzimologia , Sistema Cardiovascular/fisiopatologia , Humanos , Lisina , Lisina Acetiltransferases/metabolismo , Terapia de Alvo Molecular , Transdução de Sinais
18.
Nat Rev Cardiol ; 17(3): 170-194, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31591535

RESUMO

Reactive oxygen species (ROS)-dependent production of ROS underlies sustained oxidative stress, which has been implicated in the pathogenesis of cardiovascular diseases such as hypertension, aortic aneurysm, hypercholesterolaemia, atherosclerosis, diabetic vascular complications, cardiac ischaemia-reperfusion injury, myocardial infarction, heart failure and cardiac arrhythmias. Interactions between different oxidases or oxidase systems have been intensively investigated for their roles in inducing sustained oxidative stress. In this Review, we discuss the latest data on the pathobiology of each oxidase component, the complex crosstalk between different oxidase components and the consequences of this crosstalk in mediating cardiovascular disease processes, focusing on the central role of particular NADPH oxidase (NOX) isoforms that are activated in specific cardiovascular diseases. An improved understanding of these mechanisms might facilitate the development of novel therapeutic agents targeting these oxidase systems and their interactions, which could be effective in the prevention and treatment of cardiovascular disorders.


Assuntos
Doenças Cardiovasculares/enzimologia , NADPH Oxidases/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Animais , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/fisiopatologia , Inibidores Enzimáticos/uso terapêutico , Humanos , Isoenzimas , NADPH Oxidases/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos
19.
Int J Cardiol ; 299: 289-295, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31668506

RESUMO

BACKGROUND: We aimed to examine cardiovascular risk factors and health behaviors in patients with acute coronary syndromes (ACS) according to potential extension of eligibility criteria for protein convertase subtilisin/kexin-9 inhibitors (PCSK9i) to all patients with low-density lipoprotein cholesterol (LDL-c) equal or above 1.8 mmol/l. METHODS: In this prospective cross-sectional study, patients with ACS between 2009 and 2016 and with available LDL-c at one year were considered. We defined three mutually exclusive groups of patients according to eligibility for PCSK9i: "not eligible", "currently eligible", and "newly eligible". We explored the control of cardiovascular risk factors and health behaviors. RESULTS: Out of 3025 patients who had an ACS one year ago, 1071 (35.4%) were not eligible for PCSK9i, 415 (13.7%) were currently eligible, and 1539 (50.9%) were newly eligible. The proportion of patients with uncontrolled hypertension in the not eligible group was lower than in the group currently eligible (27.6% vs 33.6%, p = 0.02), but similar to the group newly eligible (27.6% vs 28.2%, p = 0.73). The proportion of smokers in the not eligible group was lower than in the group currently eligible (21.2% vs 28.0%, p = 0.02), but similar to the group newly eligible (21.2% vs 22.5%, p = 0.51). CONCLUSIONS: More than half of patients with ACS would be additionally eligible for PCSK9i if prescription is extended from current guidelines to all patients with LDL-c equal or above 1.8 mmol/l. Patients currently eligible for PCSK9i one year after an ACS had a worst control of cardiovascular risk factors than patients potentially newly eligible.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Síndrome Coronariana Aguda/enzimologia , Fármacos Cardiovasculares/administração & dosagem , Comportamentos Relacionados com a Saúde/efeitos dos fármacos , Pró-Proteína Convertase 9/antagonistas & inibidores , Idoso , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/enzimologia , Estudos Transversais , Inibidores Enzimáticos/administração & dosagem , Feminino , Comportamentos Relacionados com a Saúde/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Pró-Proteína Convertase 9/metabolismo , Estudos Prospectivos , Fatores de Risco
20.
Food Funct ; 10(10): 6533-6542, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31539010

RESUMO

Cardiovascular diseases are the greatest cause of death globally and are frequently associated with type 2 diabetes mellitus and metabolic syndrome, a condition including visceral obesity, hypertension, elevated triglycerides and low HDL cholesterol and hyperglycaemia. Several medicinal plants, including spices, are used in Cameroon as herbal medicines and are traditionally employed for the treatment of several ailments such as diabetes and related diseases. In this study, we chemically characterized eleven Cameroonian spice extracts and evaluated their effects on some enzyme activities relevant to carbohydrate and lipid digestion and cardio-metabolic diseases. Hydroethanolic spice extracts were characterized by GC-MS analysis and screened for their ability to modulate the activity of α-glucosidase, α-amylase, pancreatic lipase, 3-hydroxy-3-methylglutaryl-coenzyme A reductase and angiotensin-converting enzyme (ACE). Among the spice extracts tested, those from Xylopia parviflora showed the widest inhibitory spectrum, with a relevant effect on all enzyme activities. Dichrostachys glomerata and Aframomum citratum extracts were more selective. The selected and strong activity of some plants, such as that of Aframomum citratum on pancreatic lipase and that of Xylopia aethiopica on ACE, suggests their specific use in obesity and hypertension, respectively. Chemical analysis indicated that for some spice extracts such as Xylopia parviflora and Aframomum citratum their secondary metabolites (chlorogenic acid, pimaric acid, and catechin and its derivatives) could potentially justify the biological properties observed. Our findings clearly show significant inhibition of cardio-metabolic enzymes by hydroethanolic Cameroonian spice extracts, suggesting the potential usefulness of nutraceuticals derived from these plants to develop novel management strategies for obesity and diabetes complications.


Assuntos
Doenças Cardiovasculares/enzimologia , Diabetes Mellitus Tipo 2/enzimologia , Inibidores Enzimáticos/química , Extratos Vegetais/química , Plantas Medicinais/química , Camarões , Inibidores Enzimáticos/isolamento & purificação , Humanos , Peptidil Dipeptidase A/química , Peptidil Dipeptidase A/metabolismo , Extratos Vegetais/isolamento & purificação , alfa-Amilases/antagonistas & inibidores , alfa-Amilases/química , alfa-Amilases/metabolismo , alfa-Glucosidases/química , alfa-Glucosidases/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA