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1.
Cardiovasc Diabetol ; 19(1): 164, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-33004045

RESUMO

BACKGROUND: Cardiometabolic disorders may worsen Covid-19 outcomes. We investigated features and Covid-19 outcomes for patients with or without diabetes, and with or without cardiometabolic multimorbidity. METHODS: We collected and compared data retrospectively from patients hospitalized for Covid-19 with and without diabetes, and with and without cardiometabolic multimorbidity (defined as ≥ two of three risk factors of diabetes, hypertension or dyslipidaemia). Multivariate logistic regression was used to assess the risk of the primary composite outcome (any of mechanical ventilation, admission to an intensive care unit [ICU] or death) in patients with diabetes and in those with cardiometabolic multimorbidity, adjusting for confounders. RESULTS: Of 354 patients enrolled, those with diabetes (n = 81), compared with those without diabetes (n = 273), had characteristics associated with the primary composite outcome that included older age, higher prevalence of hypertension and chronic obstructive pulmonary disease (COPD), higher levels of inflammatory markers and a lower PaO2/FIO2 ratio. The risk of the primary composite outcome in the 277 patients who completed the study as of May 15th, 2020, was higher in those with diabetes (Adjusted Odds Ratio (adjOR) 2.04, 95%CI 1.12-3.73, p = 0.020), hypertension (adjOR 2.31, 95%CI: 1.37-3.92, p = 0.002) and COPD (adjOR 2.67, 95%CI 1.23-5.80, p = 0.013). Patients with cardiometabolic multimorbidity were at higher risk compared to patients with no cardiometabolic conditions (adjOR 3.19 95%CI 1.61-6.34, p = 0.001). The risk for patients with a single cardiometabolic risk factor did not differ with that for patients with no cardiometabolic risk factors (adjOR 1.66, 0.90-3.06, adjp = 0.10). CONCLUSIONS: Patients with diabetes hospitalized for Covid-19 present with high-risk features. They are at increased risk of adverse outcomes, likely because diabetes clusters with other cardiometabolic conditions.


Assuntos
Betacoronavirus , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/metabolismo , Infecções por Coronavirus/metabolismo , Diabetes Mellitus/metabolismo , Feminino , Seguimentos , Humanos , Masculino , Doenças Metabólicas/diagnóstico , Doenças Metabólicas/epidemiologia , Doenças Metabólicas/metabolismo , Pessoa de Meia-Idade , Multimorbidade/tendências , Pandemias , Pneumonia Viral/metabolismo , Prognóstico , Estudos Retrospectivos , Fatores de Risco
2.
Adv Exp Med Biol ; 1274: 71-99, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32894508

RESUMO

Bioactive lipid mediators resulting from the metabolism of polyunsaturated fatty acids (PUFA) are controlled by many pathways that regulate the levels of these mediators and maintain homeostasis to prevent disease. PUFA metabolism is driven primarily through three pathways. Two pathways, the cyclooxygenase (COX) and lipoxygenase (LO) enzymatic pathways, form metabolites that are mostly inflammatory, while the third route of metabolism results from the oxidation by the cytochrome P450 enzymes to form hydroxylated PUFA and epoxide metabolites. These epoxygenated fatty acids (EpFA) demonstrate largely anti-inflammatory and beneficial properties, in contrast to the other metabolites formed from the degradation of PUFA. Dysregulation of these systems often leads to chronic disease. Pharmaceutical targets of disease focus on preventing the formation of inflammatory metabolites from the COX and LO pathways, while maintaining the EpFA and increasing their concentration in the body is seen as beneficial to treating and preventing disease. The soluble epoxide hydrolase (sEH) is the major route of metabolism of EpFA. Inhibiting its activity increases concentrations of beneficial EpFA, and often disease states correlate to mutations in the sEH enzyme that increase its activity and decrease the concentrations of EpFA in the body. Recent approaches to increasing EpFA include synthetic mimics that replicate biological activity of EpFA while preventing their metabolism, while other approaches focus on developing small molecule inhibitors to the sEH. Increasing EpFA concentrations in the body has demonstrated multiple beneficial effects in treating many diseases, including inflammatory and painful conditions, cardiovascular disease, neurological and disease of the central nervous system. Demonstration of efficacy in so many disease states can be explained by the fundamental mechanism that EpFA have of maintaining healthy microvasculature and preventing mitochondrial and endoplasmic reticulum stress. While there are no FDA approved methods that target the sEH or other enzymes responsible for metabolizing EpFA, current clinical efforts to test for efficacy by increasing EpFA that include inhibiting the sEH or administration of EpFA mimics that block metabolism are in progress.


Assuntos
Doenças Cardiovasculares/tratamento farmacológico , Estresse do Retículo Endoplasmático , Ácidos Graxos/metabolismo , Inflamação/tratamento farmacológico , Mitocôndrias/patologia , Terapia de Alvo Molecular , Manejo da Dor , Doenças Cardiovasculares/metabolismo , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Humanos , Inflamação/patologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Dor
3.
J Cardiovasc Med (Hagerstown) ; 21(9): 630-633, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32740495

RESUMO

: ACE2 receptor has a broad expression pattern in the cellular membrane and provides a protective action against the development of cardiovascular diseases. Recently, this enzyme has become of extreme interest during the pandemic infection of COVID-19 (coronavirus disease 2019). This virus invades alveolar epithelium and cardiomyocytes using ACE2 as a transmembrane receptor. ACE2 is a counter-regulatory peptide that degrades Ang II into Ang 1-7, thereby attenuating the biological effects of the AT1 receptor. The binding between the spike protein of COVID-19 and the enzyme is crucial for the virus to enter the target cells, but whether an increase in ACE2 activity could facilitate the infection is not yet demonstrated. However, this aspect has raised many concerns about the use of ACE inhibitors or ARBs in infected patients or patients at risk of infection. It appears that cellular infection leads to a reduction in ACE2 expression and an increase in the activity of the Ang II--AT1 axis, which leads to the release of pro-inflammatory cytokines, ARDS, myocarditis, and hypercoagulability with the possibility of exacerbation of acute coronary syndrome, induction of pulmonary embolism, or appearance of disseminated intravascular coagulation. Therefore, ACE inhibitors or angiotensin receptor blocker drugs should be continued in infected patients, as their discontinuation can increase Ang II activity and induce injury to the lungs or cardiovascular system.


Assuntos
Antagonistas de Receptores de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Betacoronavirus/fisiologia , Doenças Cardiovasculares , Infecções por Coronavirus , Pandemias , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral , Internalização do Vírus , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/metabolismo , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/virologia , Humanos , Pneumonia Viral/metabolismo , Pneumonia Viral/virologia , Sistema Renina-Angiotensina/efeitos dos fármacos , Sistema Renina-Angiotensina/fisiologia , Glicoproteína da Espícula de Coronavírus/metabolismo
4.
Nat Commun ; 11(1): 4110, 2020 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-32807790

RESUMO

Hutchinson-Gilford Progeria Syndrome (HGPS) is a premature aging disease in children that leads to early death. Smooth muscle cells (SMCs) are the most affected cells in HGPS individuals, although the reason for such vulnerability remains poorly understood. In this work, we develop a microfluidic chip formed by HGPS-SMCs generated from induced pluripotent stem cells (iPSCs), to study their vulnerability to flow shear stress. HGPS-iPSC SMCs cultured under arterial flow conditions detach from the chip after a few days of culture; this process is mediated by the upregulation of metalloprotease 13 (MMP13). Importantly, double-mutant LmnaG609G/G609GMmp13-/- mice or LmnaG609G/G609GMmp13+/+ mice treated with a MMP inhibitor show lower SMC loss in the aortic arch than controls. MMP13 upregulation appears to be mediated, at least in part, by the upregulation of glycocalyx. Our HGPS-SMCs chip represents a platform for developing treatments for HGPS individuals that may complement previous pre-clinical and clinical treatments.


Assuntos
Metaloproteinase 13 da Matriz/metabolismo , Miócitos de Músculo Liso/metabolismo , Animais , Biotecnologia/métodos , Doenças Cardiovasculares/metabolismo , Feminino , Frequência Cardíaca/efeitos dos fármacos , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/efeitos dos fármacos , Células-Tronco Pluripotentes Induzidas/metabolismo , Lamina Tipo A/genética , Lamina Tipo A/metabolismo , Masculino , Inibidores de Metaloproteinases de Matriz/farmacologia , Camundongos , Camundongos Mutantes , Miócitos de Músculo Liso/efeitos dos fármacos , Progéria/metabolismo , Progéria/patologia , Proteômica/métodos
5.
Pathol Res Pract ; 216(9): 153086, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32825954

RESUMO

A novel coronavirus SARS-CoV-2 causes acute respiratory distress syndrome (ARDS) with cardiovascular and multiple organ failure till death. The main mechanisms of virus internalization and interaction with the host are down-regulation or upregulation of the ACE2 receptor, the surface glycoprotein competition mechanism for the binding of porphyrin to iron in heme formation as well as interference with the immune system. The interference on renin-angiotensin-aldosterone system (RAAS) activation, heme formation, and the immune response is responsible for infection diffusion, endothelial dysfunction, vasoconstriction, oxidative damage and releasing of inflammatory mediators. The main pathological findings are bilateral interstitial pneumonia with diffuse alveolar damage (DAD). Because ACE receptor is also present in the endothelium of other districts as well as in different cell types, and as porphyrins are transporters in the blood and other biological liquids of iron forming heme, which is important in the assembly of the hemoglobin, myoglobin and the cytochromes, multiorgan damage occurs both primitive and secondary to lung damage. More relevantly, myocarditis, acute myocardial infarction, thromboembolism, and disseminated intravasal coagulation (DIC) are described as complications in patients with poor outcome. Here, we investigated the role of SARSCoV-2 on the cardiovascular system and in patients with cardiovascular comorbidities, and possible drug interference on the heart.


Assuntos
Betacoronavirus/patogenicidade , Doenças Cardiovasculares/etiologia , Infecções por Coronavirus/virologia , Pulmão/virologia , Pneumonia Viral/virologia , Doenças Cardiovasculares/metabolismo , Sistema Cardiovascular/virologia , Infecções por Coronavirus/complicações , Humanos , Pulmão/metabolismo , Pandemias , Pneumonia Viral/complicações , Sistema Renina-Angiotensina/fisiologia
6.
Cardiovasc Ther ; 2020: 9397109, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32821285

RESUMO

Chronic systemic inflammation contributes to cardiovascular disease (CVD) and correlates with the abundance of acute phase response (APR) proteins in the liver and plasma. Bromodomain and extraterminal (BET) proteins are epigenetic readers that regulate inflammatory gene transcription. We show that BET inhibition by the small molecule apabetalone reduces APR gene and protein expression in human hepatocytes, mouse models, and plasma from CVD patients. Steady-state expression of serum amyloid P, plasminogen activator inhibitor 1, and ceruloplasmin, APR proteins linked to CVD risk, is reduced by apabetalone in cultured hepatocytes and in humanized mouse liver. In cytokine-stimulated hepatocytes, apabetalone reduces the expression of C-reactive protein (CRP), alpha-2-macroglobulin, and serum amyloid P. The latter two are also reduced by apabetalone in the liver of endotoxemic mice. BET knockdown in vitro also counters cytokine-mediated induction of the CRP gene. Mechanistically, apabetalone reduces the cytokine-driven increase in BRD4 BET occupancy at the CRP promoter, confirming that transcription of CRP is BET-dependent. In patients with stable coronary disease, plasma APR proteins CRP, IL-1 receptor antagonist, and fibrinogen γ decrease after apabetalone treatment versus placebo, resulting in a predicted downregulation of the APR pathway and cytokine targets. We conclude that CRP and components of the APR pathway are regulated by BET proteins and that apabetalone counters chronic cytokine signaling in patients.


Assuntos
Anti-Inflamatórios/farmacologia , Proteína C-Reativa/metabolismo , Doenças Cardiovasculares/tratamento farmacológico , Citocinas/metabolismo , Endotoxemia/tratamento farmacológico , Epigênese Genética/efeitos dos fármacos , Proteínas Nucleares/metabolismo , Quinazolinonas/farmacologia , Fatores de Transcrição/metabolismo , Animais , Sítios de Ligação , Proteína C-Reativa/genética , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/metabolismo , Células Cultivadas , Ceruloplasmina/genética , Ceruloplasmina/metabolismo , Citocinas/genética , Modelos Animais de Doenças , Endotoxemia/genética , Endotoxemia/metabolismo , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Proteínas Nucleares/genética , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Regiões Promotoras Genéticas , Componente Amiloide P Sérico/metabolismo , Transdução de Sinais , Fatores de Transcrição/genética , alfa-Macroglobulinas/genética , alfa-Macroglobulinas/metabolismo
7.
Cells ; 9(9)2020 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-32859053

RESUMO

Extracellular vesicles are a heterogeneous group of cell-derived membranous structures comprising of exosomes, apoptotic bodies, and microvesicles. Of the extracellular vesicles, exosomes are the most widely sorted and extensively explored for their contents and function. The size of the nanovesicular structures (exosomes) range from 30 to 140 nm and are present in various biological fluids such as saliva, plasma, urine etc. These cargo-laden extracellular vesicles arise from endosome-derived multivesicular bodies and are known to carry proteins and nucleic acids. Exosomes are involved in multiple physiological and pathological processes, including cellular senescence. Exosomes mediate signaling crosstalk and play a critical role in cell-cell communications. Exosomes have evolved as potential biomarkers for aging-related diseases. Aging, a physiological process, involves a progressive decline of function of organs with a loss of homeostasis and increasing probability of illness and death. The review focuses on the classic view of exosome biogenesis, biology, and age-associated changes. Owing to their ability to transport biological information among cells, the review also discusses the interplay of senescent cell-derived exosomes with the aging process, including the susceptibility of the aging population to COVID-19 infections.


Assuntos
Envelhecimento/metabolismo , Doenças Cardiovasculares/metabolismo , Comunicação Celular , Senescência Celular , Infecções por Coronavirus/metabolismo , Diabetes Mellitus/metabolismo , Exossomos/metabolismo , Vesículas Extracelulares/metabolismo , Doenças Neurodegenerativas/metabolismo , Pneumonia Viral/metabolismo , Idoso , Idoso de 80 Anos ou mais , Animais , Betacoronavirus , Biomarcadores/metabolismo , Infecções por Coronavirus/virologia , Humanos , Camundongos , Pandemias , Pneumonia Viral/virologia
8.
Adv Exp Med Biol ; 1265: 39-56, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32761569

RESUMO

Cardiovascular disease is the major cause of global mortality and disability. Abundant evidence indicates that amino acids play a fundamental role in cardiovascular physiology and pathology. Decades of research established the importance of L-arginine in promoting vascular health through the generation of the gas nitric oxide. More recently, L-glutamine, L-tryptophan, and L-cysteine have also been shown to modulate vascular function via the formation of a myriad of metabolites, including a number of gases (ammonia, carbon monoxide, hydrogen sulfide, and sulfur dioxide). These amino acids and their metabolites preserve vascular homeostasis by regulating critical cellular processes including proliferation, migration, differentiation, apoptosis, contractility, and senescence. Furthermore, they exert potent anti-inflammatory and antioxidant effects in the circulation, and block the accumulation of lipids within the arterial wall. They also mitigate known risk factors for cardiovascular disease, including hypertension, hyperlipidemia, obesity, and diabetes. However, in some instances, the metabolism of these amino acids through discrete pathways yields compounds that fosters vascular disease. While supplementation with amino acid monotherapy targeting the deficiency has ameliorated arterial disease in many animal models, this approach has been less successful in the clinic. A more robust approach combining amino acid supplementation with antioxidants, anti-inflammatory agents, and/or specific amino acid enzymatic pathway inhibitors may prove more successful. Alternatively, supplementation with amino acid-derived metabolites rather than the parent molecule may elicit beneficial effects while bypassing potentially harmful pathways of metabolism. Finally, there is an emerging recognition that circulating levels of multiple amino acids are perturbed in vascular disease and that a more holistic approach that targets all these amino acid derangements is required to restore circulatory function in diseased blood vessels.


Assuntos
Aminoácidos/metabolismo , Sistema Cardiovascular/metabolismo , Saúde , Animais , Doenças Cardiovasculares/metabolismo , Endotélio Vascular/metabolismo , Humanos , Doenças Metabólicas/metabolismo , Óxido Nítrico/metabolismo
9.
Diabetes Res Clin Pract ; 167: 108349, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32712124

RESUMO

AIM: While there are rampant deaths reported worldwide due to novel corona virus (COVID-19) on one side, hypertension, diabetes and renal failure are emerging comorbidities with mortality risk due to respiratory failure on the other side. The link of these morbidities with renin angiotensin system (RAS) and angiotensin converting enzyme-2 (ACE2) as the site of the multiplication of COVID-19 has widely been accepted. The objective of this research report was to delineate the clinical characteristics with COVID-19 infection with RAS and to consider its significance not just for the search of novel antiviral drugs, but for the management and prevention of death of patients with COVID-19. METHODS: It was a retrospective case series analysis of demographic and clinical data with associated comorbidities of 206 deaths reported in India up to 10th April 2020. The data were available from the official release from Ministry of Health and Family welfare, Government of India. This was followed by a literature search to correlate the available evidence for their possible relationship with RAS. RESULTS: The demographic data were consistent with those reported from other countries. The death (53.4%) was more common in patients with age above 60 years and men (69.3%) were more susceptible as compared to women (30.68%).We found that 50.5% of the deceased patients had pre-existing comorbidities. Diabetes and hypertension were the major comorbidities in 27.8% and 22.1% of the deceased cases respectively. Although respiratory and cardiac problems were prevalent at the time of death, the pre-existing pulmonary disease was comparatively less prevalent. Only 13.6% of the deceased were having pre-existing respiratory problems and 6.2% had cardiac ailments. We could correlate the reports that RAS plays a significant role in the prognosis of the disease. CONCLUSIONS: Patients with cardiovascular diseases, diabetes mellitus and hypertension are at greater risk for developing COVID-19 infection. There may be massive derangement of the entire RAS after the attack of COVID-19 and hence, patients with these pre-existing comorbidities and on ACE inhibitors or angiotensin receptor blockers should be monitored carefully considering the role of RAS in the prognosis of COVID-19 infections.


Assuntos
Infecções por Coronavirus/mortalidade , Diabetes Mellitus/epidemiologia , Hipertensão/epidemiologia , Pneumonia Viral/mortalidade , Sistema Renina-Angiotensina , Adulto , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Betacoronavirus , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/metabolismo , Comorbidade , Infecções por Coronavirus/metabolismo , Diabetes Mellitus/metabolismo , Feminino , Cardiopatias/tratamento farmacológico , Cardiopatias/epidemiologia , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/metabolismo , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Pandemias , Peptidil Dipeptidase A , Pneumonia Viral/metabolismo , Doenças Respiratórias/epidemiologia , Estudos Retrospectivos
10.
Physiol Rev ; 100(4): 1599-1619, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32666886

RESUMO

Sentrin/small ubiquitin-like modifier (SUMO) is protein modification pathway that regulates multiple biological processes, including cell division, DNA replication/repair, signal transduction, and cellular metabolism. In this review, we will focus on recent advances in the mechanisms of disease pathogenesis, such as cancer, diabetes, seizure, and heart failure, which have been linked to the SUMO pathway. SUMO is conjugated to lysine residues in target proteins through an isopeptide linkage catalyzed by SUMO-specific activating (E1), conjugating (E2), and ligating (E3) enzymes. In steady state, the quantity of SUMO-modified substrates is usually a small fraction of unmodified substrates due to the deconjugation activity of the family Sentrin/SUMO-specific proteases (SENPs). In contrast to the complexity of the ubiquitination/deubiquitination machinery, the biochemistry of SUMOylation and de-SUMOylation is relatively modest. Specificity of the SUMO pathway is achieved through redox regulation, acetylation, phosphorylation, or other posttranslational protein modification of the SUMOylation and de-SUMOylation enzymes. There are three major SUMOs. SUMO-1 usually modifies a substrate as a monomer; however, SUMO-2/3 can form poly-SUMO chains. The monomeric SUMO-1 or poly-SUMO chains can interact with other proteins through SUMO-interactive motif (SIM). Thus SUMO modification provides a platform to enhance protein-protein interaction. The consequence of SUMOylation includes changes in cellular localization, protein activity, or protein stability. Furthermore, SUMO may join force with ubiquitin to degrade proteins through SUMO-targeted ubiquitin ligases (STUbL). After 20 yr of research, SUMO has been shown to play critical roles in most, if not all, biological pathways. Thus the SUMO enzymes could be targets for drug development to treat human diseases.


Assuntos
Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/metabolismo , Imunidade Adaptativa/fisiologia , Animais , Doenças Cardiovasculares/metabolismo , Diabetes Mellitus/metabolismo , Humanos , Neoplasias/metabolismo , Processamento de Proteína Pós-Traducional , Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/genética
11.
Rev Cardiovasc Med ; 21(2): 225-240, 2020 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-32706211

RESUMO

In spite of medical advances, cardiovascular disease remains a significant concern, imposing a great burden upon the economy and public health of nations by causing the highest morbidity and mortality cases globally. Moreover, it is well established that inflammation is closely linked to the pathogenesis of cardiovascular diseases. Hence, targeting inflammation seems to be a promising strategy in reducing cardiovascular risks. Currently, the importance of natural products in modern medicine is well recognised and continues to be of interest to the pharmaceutical industry. Phenolic acids are a class of phytochemical compounds that are well-known for their health benefits. They consists of various phytochemical constituents and have been widely studied in various disease models. Research involving both animals and humans has proven that phenolic acids possess cardioprotective properties such as anti-hypertensive, anti-hyperlipidemia, anti-fibrotic and anti-hypertrophy activity. Furthermore, numerous studies have proven that phenolic acids in phytochemical constituents such as gallic acid, caffeic acid and chlorogenic acid are promising anti-inflammatory agents. Hence, in this review, we outline and review recent evidence on the role of phenolic acids and their anti-inflammatory significance in studies published during the last 5 years. We also discuss their possible mechanisms of action in modulating inflammation related to cardiovascular disease.


Assuntos
Anti-Inflamatórios/administração & dosagem , Doenças Cardiovasculares/prevenção & controle , Sistema Cardiovascular/efeitos dos fármacos , Dieta , Hidroxibenzoatos/administração & dosagem , Mediadores da Inflamação/metabolismo , Inflamação/prevenção & controle , Animais , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/fisiopatologia , Sistema Cardiovascular/metabolismo , Sistema Cardiovascular/fisiopatologia , Humanos , Inflamação/metabolismo , Inflamação/fisiopatologia , Transdução de Sinais
12.
Rev Cardiovasc Med ; 21(2): 253-261, 2020 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-32706213

RESUMO

It is known that functional defects of GATA binding protein 5 (GATA5), an important member of GATA transcription factor family, could cause multiple congenital defects. However, the mechanisms of this transcription factor in cardiovascular diseases are still little known. Finding a genetic approach should help with understanding the possible roles of GATA5 in different cardiovascular diseases and purpose it as a possible therapeutic agent. Hence, this review is divided into three chapters to summarize the roles and main regulatory mechanisms of GATA5 in hypertension, arrhythmia and congenital heart disease, respectively. In each chapter, this review firstly introduces the roles of GATA5 mutations, and then discusses the main regulatory mechanisms of GATA5 in the corresponding diseases (Such as the endothelial dysfunction signaling pathway in the chapter of hypertension, GATA5-NaV1.5 signaling pathway in the chapter of arrhythmia, GATA5-HEY2 and GATA5-Nodal signaling pathway in the chapter of congenital heart disease). Additionally, based on these regulatory networks, it is also speculated that abnormal methylation of the GATA5 gene promoter may lead to cardiovascular diseases such as congenital heart disease. This conjecture is proposed to enrich the regulatory networks of GATA5 and provide a theoretical basis for diagnosis and treatment of cardiovascular diseases.


Assuntos
Doenças Cardiovasculares/metabolismo , Sistema Cardiovascular/metabolismo , Fator de Transcrição GATA5/metabolismo , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/fisiopatologia , Sistema Cardiovascular/fisiopatologia , Fator de Transcrição GATA5/genética , Redes Reguladoras de Genes , Predisposição Genética para Doença , Humanos , Mutação , Canal de Sódio Disparado por Voltagem NAV1.5/genética , Canal de Sódio Disparado por Voltagem NAV1.5/metabolismo , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Transdução de Sinais
13.
Ther Adv Cardiovasc Dis ; 14: 1753944720934937, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32611276

RESUMO

Ivabradine is a pure heart-rate lowering drug that is nowadays used, accordingly to the last ESC Guidelines, to reduce mortality and heart failure (HF) hospitalization in patients with HF with reduced ejection fraction and in symptomatic patiens with inappropriate sinus tachycardia. Moreover, interesting effect of ivabradine on endothelial and myocardial function and on oxidative stress and inflamation pathways are progressively emerging. The aim of this paper is to highlight newer evidences about ivabradine effect (and consequently possible future application of the drug) in pathological settings different from guidelines-based clinical practice.


Assuntos
Fármacos Cardiovasculares/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Endotélio Vascular/efeitos dos fármacos , Ivabradina/uso terapêutico , Animais , Função Atrial/efeitos dos fármacos , Fármacos Cardiovasculares/efeitos adversos , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/fisiopatologia , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiopatologia , Hemodinâmica/efeitos dos fármacos , Humanos , Mediadores da Inflamação/metabolismo , Ivabradina/efeitos adversos , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Função Ventricular/efeitos dos fármacos
14.
Arch Cardiovasc Dis ; 113(8-9): 564-571, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32680738

RESUMO

The mitochondria produce specific peptides-mitochondrial-derived peptides-that mediate the transcriptional stress response by their translocation into the nucleus and interaction with deoxyribonucleic acid. Mitochondrial-derived peptides are regulators of metabolism. This class of peptides comprises humanin, mitochondrial open reading frame of the 12S ribosomal ribonucleic acid type c (MOTS-c) and small humanin-like peptides (SHLPs). Humanin inhibits mitochondrial complex 1 activity and limits the level of oxidative stress in the cell. Data show that mitochondrial-derived peptides have a role in improving metabolic diseases, such as type 2 diabetes. Perhaps humanin can be used as a marker for mitochondrial function in cardiovascular disease or as a pharmacological strategy in patients with endothelial dysfunction. The goal of this review is to discuss the newly emerging functions of humanin, and its biological role in cardiovascular disorders.


Assuntos
Doenças Cardiovasculares/metabolismo , Sistema Cardiovascular/metabolismo , Mediadores da Inflamação/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Mitocôndrias/metabolismo , Animais , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/fisiopatologia , Sistema Cardiovascular/fisiopatologia , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Mitocôndrias/genética , Estresse Oxidativo , Transdução de Sinais , Regulação para Cima
15.
Nat Rev Cardiol ; 17(9): 543-558, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32690910

RESUMO

Coronavirus disease 2019 (COVID-19), caused by a strain of coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic that has affected the lives of billions of individuals. Extensive studies have revealed that SARS-CoV-2 shares many biological features with SARS-CoV, the zoonotic virus that caused the 2002 outbreak of severe acute respiratory syndrome, including the system of cell entry, which is triggered by binding of the viral spike protein to angiotensin-converting enzyme 2. Clinical studies have also reported an association between COVID-19 and cardiovascular disease. Pre-existing cardiovascular disease seems to be linked with worse outcomes and increased risk of death in patients with COVID-19, whereas COVID-19 itself can also induce myocardial injury, arrhythmia, acute coronary syndrome and venous thromboembolism. Potential drug-disease interactions affecting patients with COVID-19 and comorbid cardiovascular diseases are also becoming a serious concern. In this Review, we summarize the current understanding of COVID-19 from basic mechanisms to clinical perspectives, focusing on the interaction between COVID-19 and the cardiovascular system. By combining our knowledge of the biological features of the virus with clinical findings, we can improve our understanding of the potential mechanisms underlying COVID-19, paving the way towards the development of preventative and therapeutic solutions.


Assuntos
Betacoronavirus/fisiologia , Doenças Cardiovasculares , Infecções por Coronavirus , Pandemias , Pneumonia Viral , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/fisiopatologia , Comorbidade , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/fisiopatologia , Gerenciamento Clínico , Humanos , Pneumonia Viral/epidemiologia , Pneumonia Viral/metabolismo , Pneumonia Viral/fisiopatologia , Fatores de Risco
16.
Am J Physiol Heart Circ Physiol ; 319(2): H488-H506, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32618516

RESUMO

Although chronic stress is an important risk factor for cardiovascular diseases (CVD) onset, the underlying mechanisms driving such pathophysiological complications remain relatively unknown. Here, dysregulation of innate stress response systems and the effects of downstream mediators are strongly implicated, with the vascular endothelium emerging as a primary target of excessive glucocorticoid and catecholamine action. Therefore, this review article explores the development of stress-related endothelial dysfunction by focusing on the following: 1) assessing the phenomenon of stress and complexities surrounding this notion, 2) discussing mechanistic links between chronic stress and endothelial dysfunction, and 3) evaluating the utility of various preclinical models currently employed to study mechanisms underlying the onset of stress-mediated complications such as endothelial dysfunction. The data reveal that preclinical models play an important role in our efforts to gain an increased understanding of mechanisms underlying stress-mediated endothelial dysfunction. It is our understanding that this provides a good foundation going forward, and we propose that further efforts should be made to 1) more clearly define the concept of stress and 2) standardize protocols of animal models with specific guidelines to better indicate the mental complications that are simulated.


Assuntos
Doenças Cardiovasculares/etiologia , Endotélio Vascular/fisiopatologia , Estresse Psicológico/complicações , Animais , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/fisiopatologia , Doenças Cardiovasculares/psicologia , Catecolaminas/metabolismo , Doença Crônica , Modelos Animais de Doenças , Endotélio Vascular/metabolismo , Glucocorticoides/metabolismo , Humanos , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipotálamo-Hipofisário/fisiopatologia , Fatores de Risco , Transdução de Sinais , Estresse Psicológico/metabolismo , Estresse Psicológico/fisiopatologia , Estresse Psicológico/psicologia
19.
Biochem Pharmacol ; 178: 114114, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32579957

RESUMO

The coronavirus disease 2019 (COVID-19), elicited by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is a pandemic public health emergency of global concern. Other than the profound severe pulmonary damage, SARS-CoV-2 infection also leads to a series of cardiovascular abnormalities, including myocardial injury, myocarditis and pericarditis, arrhythmia and cardiac arrest, cardiomyopathy, heart failure, cardiogenic shock, and coagulation abnormalities. Meanwhile, COVID-19 patients with preexisting cardiovascular diseases are often at a much higher risk of increased morbidity and mortality. Up-to-date, a number of mechanisms have been postulated for COVID-19-associated cardiovascular damage including SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) activation, cytokine storm, hypoxemia, stress and cardiotoxicity of antiviral drugs. In this context, special attention should be given towards COVID-19 patients with concurrent cardiovascular diseases, and special cardiovascular attention is warranted for treatment of COVID-19.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Doenças Cardiovasculares/tratamento farmacológico , Infecções por Coronavirus/tratamento farmacológico , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/tratamento farmacológico , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Antimaláricos/farmacologia , Antimaláricos/uso terapêutico , Antivirais/farmacologia , Betacoronavirus/fisiologia , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/metabolismo , Cloroquina/farmacologia , Cloroquina/uso terapêutico , Infecções por Coronavirus/complicações , Infecções por Coronavirus/virologia , Humanos , Hidroxicloroquina/farmacologia , Hidroxicloroquina/uso terapêutico , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/virologia , Internalização do Vírus/efeitos dos fármacos
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