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1.
Crit Care ; 25(1): 309, 2021 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-34461956

RESUMO

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2021. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2021 . Further information about the Annual Update in Intensive Care and Emergency Medicine is available from https://link.springer.com/bookseries/8901 .


Assuntos
Aorta/fisiopatologia , Contrapulsação/normas , Choque Cardiogênico/cirurgia , Procedimentos Cirúrgicos Cardíacos/métodos , Procedimentos Cirúrgicos Cardíacos/normas , Procedimentos Cirúrgicos Cardíacos/estatística & dados numéricos , Contrapulsação/métodos , Contrapulsação/estatística & dados numéricos , Humanos
2.
Afr Health Sci ; 21(1): 96-104, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34394286

RESUMO

Background: The importance of monocyte count-to-HDL-cholesterol ratio (MHR) in cardio- vascular diseases has been shown in various studies. Ascending aortic dilatation (AAD) is a common complication in the patients with bicuspid aortic valve. In this study, we aimed to investigate the relationship between MHR and the presence of aortic dilatation in the patients with bicuspid aortic valve. Methods: The study population included totally 347 patients with bicuspid aortic valve.169 patients with aortic dilatation (ascending aorta diameter ≥ 4.0 cm) and 178 patients with no aortic dilatation. Echocardiographic and laboratory measurement was done and compared between groups. Results: The mean age of the participants was 44.7 ± 15.4 years and average ascending aorta diameter was 3.2 ± 0.3 cm in dilatation negative group and 4.4 ± 0.4 cm in positive group. MHR was significantly increased in in patients with aortic dilatation. MHR and uric acid level was independently associated with the presence of aortic dilatation in the patients with bicuspid aortic valve. Conclusion: We found a significant relationship between MHR and aortic dilatation in the patients with bicuspid aortic valve.


Assuntos
Aorta/fisiopatologia , Valva Aórtica/anormalidades , HDL-Colesterol , LDL-Colesterol/sangue , Dilatação Patológica/diagnóstico por imagem , Doenças das Valvas Cardíacas/sangue , Monócitos , Adulto , Idoso , Valva Aórtica/patologia , Doença da Válvula Aórtica Bicúspide , Dilatação Patológica/complicações , Ecocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
3.
Nutrients ; 13(8)2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34445015

RESUMO

Oxidative stress is involved in the metabolic dysregulation of type 2 diabetes (DM2). Acrocomia aculeata (Aa) fruit pulp has been described for the treatment of several diseases, and recently we have proved that its leaves have phenolic compounds with a marked antioxidant effect. We aimed to assess whether they can improve metabolic, redox and vascular functions in DM2. Control Wistar (W-Ctrl) and non-obese type 2 diabetic Goto-Kakizaki (GK-Ctrl) rats were treated for 30 days with 200 mg.kg-1 aqueous extract of Aa (EA-Aa) (Wistar, W-EA-Aa/GK, GK-EA-Aa). EA-Aa was able to reduce fasting glycaemia and triglycerides of GK-EA-Aa by improving proteins related to glucose and lipid metabolism, such as GLUT-4, PPARγ, AMPK, and IR, when compared to GK-Ctrl. It also improved viability of 3T3-L1 pre-adipocytes exposed by H2O2. EA-Aa also increased the levels of catalase in the aorta and kidney, reduced oxidative stress and increased relaxation of the aorta in GK-treated rats in relation to GK-Ctrl, in addition to the protective effect against oxidative stress in HMVec-D cells. We proved the direct antioxidant potential of the chemical compounds of EA-Aa, the increase in antioxidant defences in a tissue-specific manner and hypoglycaemic properties, improving vascular function in type 2 diabetes. EA-Aa and its constituents may have a therapeutic potential for the treatment of DM2 complications.


Assuntos
Antioxidantes/farmacologia , Aorta/efeitos dos fármacos , Arecaceae , Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Angiopatias Diabéticas/tratamento farmacológico , Hipoglicemiantes/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Vasodilatação/efeitos dos fármacos , Células 3T3-L1 , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Animais , Antioxidantes/isolamento & purificação , Aorta/metabolismo , Aorta/fisiopatologia , Arecaceae/química , Biomarcadores/sangue , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Angiopatias Diabéticas/etiologia , Angiopatias Diabéticas/metabolismo , Angiopatias Diabéticas/fisiopatologia , Modelos Animais de Doenças , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Frutas , Humanos , Hipoglicemiantes/isolamento & purificação , Lipídeos/sangue , Masculino , Camundongos , Extratos Vegetais/isolamento & purificação , Ratos Wistar
4.
Am J Physiol Heart Circ Physiol ; 321(2): H424-H434, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34213389

RESUMO

In a progressively aging population, it is of utmost importance to develop reliable, noninvasive, and cost-effective tools to estimate biomarkers that can be indicative of cardiovascular risk. Various pathophysiological conditions are associated to changes in the total arterial compliance (CT), and thus, its estimation via an accurate and simple method is valuable. Direct noninvasive measurement of CT is not feasible in the clinical practice. Previous methods exist for indirect estimation of CT, which, however, require noninvasive, yet complex and expensive, recordings of the central pressure and flow. Here, we introduce a novel, noninvasive method for estimating CT from a single carotid waveform measurement using regression analysis. Features were extracted from the carotid wave and were combined with demographic data. A prediction pipeline was adopted for estimating CT using, first, a feature-based regression analysis and, second, the raw carotid pulse wave. The proposed methodology was appraised using the large human cohort (N = 2,256) of the Asklepios study. Accurate estimates of CT were yielded for both prediction schemes, namely, r = 0.83 and normalized root mean square error (nRMSE) = 9.58% for the feature-based model, and r = 0.83 and nRSME = 9.67% for the model that used the raw signal. The major advantage of this method pertains to the simplification of the technique offering easily applicable and convenient CT monitoring. Such an approach could offer promising applications, ranging from fast and cost-efficient hemodynamical monitoring by the physician to integration in wearable technologies.NEW & NOTEWORTHY This article introduces a novel artificial intelligence method to estimate total arterial compliance (CT) via exploiting the information provided by an uncalibrated carotid blood pressure waveform as well as typical clinical variables. The major finding of this study is that CT, which is usually acquired using both pressure and flow waveforms, can be accurately derived by the use of the pressure wave alone. This method could potentially facilitate easily applicable and convenient monitoring of CT.


Assuntos
Aorta/fisiopatologia , Artérias Carótidas/fisiopatologia , Rigidez Vascular/fisiologia , Adulto , Aorta/fisiologia , Artérias Carótidas/fisiologia , Complacência (Medida de Distensibilidade) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Onda de Pulso
5.
Am J Physiol Heart Circ Physiol ; 321(2): H435-H445, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34242094

RESUMO

Arterial stiffening, a characteristic feature of obesity and type 2 diabetes, contributes to the development and progression of cardiovascular diseases (CVD). Currently, no effective prophylaxis or therapeutics is available to prevent or treat arterial stiffening. A better understanding of the molecular mechanisms underlying arterial stiffening is vital to identify newer targets and strategies to reduce CVD burden. A major contributor to arterial stiffening is increased collagen deposition. In the 5'-untranslated regions of mRNAs encoding for type I collagen, an evolutionally conserved stem-loop (SL) structure plays an essential role in its stability and post-transcriptional regulation. Here, we show that feeding a high-fat/high-sucrose (HFHS) diet for 28 wk increases adiposity, insulin resistance, and blood pressure in male wild-type littermates. Moreover, arterial stiffness, assessed in vivo via aortic pulse wave velocity, and ex vivo using atomic force microscopy in aortic explants or pressure myography in isolated femoral and mesenteric arteries, was also increased in those mice. Notably, all these indices of arterial stiffness, along with collagen type I levels in the vasculature, were reduced in HFHS-fed mice harboring a mutation in the 5'SL structure, relative to wild-type littermates. This protective vascular phenotype in 5'SL-mutant mice did not associate with a reduction in insulin resistance or blood pressure. These findings implicate the 5'SL structure as a putative therapeutic target to prevent or reverse arterial stiffening and CVD associated with obesity and type 2 diabetes.NEW & NOTEWORTHY In the 5'-untranslated (UTR) regions of mRNAs encoding for type I collagen, an evolutionally conserved SL structure plays an essential role in its stability and posttranscriptional regulation. We demonstrate that a mutation of the SL mRNA structure in the 5'-UTR decreases collagen type I deposition and arterial stiffness in obese mice. Targeting this evolutionarily conserved SL structure may hold promise in the management of arterial stiffening and CVD associated with obesity and type 2 diabetes.


Assuntos
Aorta/fisiopatologia , Doenças Cardiovasculares/genética , Colágeno Tipo I/genética , Sequências Repetidas Invertidas/genética , Obesidade/fisiopatologia , RNA Mensageiro/genética , Rigidez Vascular/genética , Regiões 5' não Traduzidas/genética , Adiposidade , Animais , Doenças Cardiovasculares/fisiopatologia , Dieta Hiperlipídica , Sacarose na Dieta , Artéria Femoral/fisiopatologia , Resistência à Insulina , Masculino , Artérias Mesentéricas/fisiopatologia , Camundongos , Microscopia de Força Atômica , Mutação , Análise de Onda de Pulso
6.
Am J Physiol Heart Circ Physiol ; 321(2): H353-H368, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34142887

RESUMO

Arterial stiffness, a consequence of smoking, is an underlying risk factor of cardiovascular diseases. Epoxyeicosatrienoic acids (EETs), hydrolyzed by soluble epoxide hydrolase (sEH), have beneficial effects against vascular dysfunction. However, the role of sEH knockout in nicotine-induced arterial stiffness was not characterized. We hypothesized that sEH knockout could prevent nicotine-induced arterial stiffness. In the present study, Ephx2 (the gene encodes sEH enzyme) null (Ephx2-/-) mice and wild-type (WT) littermate mice were infused with or without nicotine and administered with or without nicotinamide [NAM, sirtuin-1 (SIRT1) inhibitor] simultaneously for 4 wk. Nicotine treatment increased sEH expression and activity in the aortas of WT mice. Nicotine infusion significantly induced vascular remodeling, arterial stiffness, and SIRT1 deactivation in WT mice, which was attenuated in Ephx2 knockout mice (Ephx2-/- mice) without NAM treatment. However, the arterial protective effects were gone in Ephx2-/- mice with NAM treatment. In vitro, 11,12-EET treatment attenuated nicotine-induced matrix metalloproteinase 2 (MMP2) upregulation via SIRT1-mediated yes-associated protein (YAP) deacetylation. In conclusion, sEH knockout attenuated nicotine-induced arterial stiffness and vascular remodeling via SIRT1-induced YAP deacetylation.NEW & NOTEWORTHY We presently show that sEH knockout repressed nicotine-induced arterial stiffness and extracellular matrix remodeling via SIRT1-induced YAP deacetylation, which highlights that sEH is a potential therapeutic target in smoking-induced arterial stiffness and vascular remodeling.


Assuntos
Aorta/efeitos dos fármacos , Epóxido Hidrolases/genética , Niacinamida/farmacologia , Nicotina/farmacologia , Agonistas Nicotínicos/farmacologia , Sirtuína 1/metabolismo , Rigidez Vascular/efeitos dos fármacos , Complexo Vitamínico B/farmacologia , Ácido 8,11,14-Eicosatrienoico/análogos & derivados , Ácido 8,11,14-Eicosatrienoico/farmacologia , Proteínas Adaptadoras de Transdução de Sinal/efeitos dos fármacos , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Aorta/metabolismo , Aorta/fisiopatologia , Metaloproteinase 2 da Matriz/efeitos dos fármacos , Metaloproteinase 2 da Matriz/genética , Camundongos , Camundongos Knockout , Sirtuína 1/antagonistas & inibidores , Sirtuína 1/efeitos dos fármacos , Rigidez Vascular/genética , Vasodilatadores/farmacologia
7.
Life Sci ; 280: 119731, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34144054

RESUMO

AIMS: Canagliflozin is an antidiabetic agent which lowers blood glucose levels by inhibiting the glucose reabsorption machinery in the proximal tubules. There have not been conducted any study on its direct impact on hypercholesterolemia and associated vascular disorders independently of blood glucose lowering activity. MATERIALS AND METHODS: Rabbits were arranged in 3 groups: Group 1 (Control): regular rabbit chow; Group 2 (HCD): 1% cholesterol-enriched chow was given to rabbits for 4 weeks; Group 3 (HCD-CANA): 1% cholesterol-enriched chow was fed to rabbits concurrently with canagliflozin (10 mg/kg/day, orally) for 4 weeks. At the end of experiment, blood and tissue samples were obtained for biochemical, histological, immunohistochemical, and vascular reactivity assessment. KEY FINDINGS: When statistically compared to Control (P < 0.05), HCD showed a significant increase in the serum triglycerides, low-density lipoprotein, total cholesterol, C-reactive protein, alkaline phosphatase, alanine aminotransferase and aspartate aminotransferase. Furthermore, a significant decrease was seen in both liver and aortic levels of glutathione peroxidase and superoxide dismutase concurrently with a significant elevation in malondialdehyde levels. Aortic levels of nitrate/nitrite ratio were significantly elevated. Acetylcholine-induced relaxation was impaired as the Emax decreased significantly in aortae. Moreover, a significant increase was seen in the level of aortic intima/media ratio. Canagliflozin treatment significantly improved vascular function, lipid profile and inflammation and reduced liver injury. SIGNIFICANCE: Our data suggest that SGLT-2 inhibition via canagliflozin not only possesses an antihyperglycemic activity, but also improves hypercholesterolemia, vascular and liver function in dietary-induced hypercholesterolemia in the rabbit.


Assuntos
Aorta/efeitos dos fármacos , Canagliflozina/uso terapêutico , Hipercolesterolemia/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Fígado/efeitos dos fármacos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Animais , Aorta/fisiopatologia , Colesterol na Dieta/efeitos adversos , Hipercolesterolemia/sangue , Hipercolesterolemia/etiologia , Hipercolesterolemia/fisiopatologia , Lipídeos/sangue , Fígado/fisiopatologia , Masculino , Coelhos
8.
Molecules ; 26(10)2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-34064778

RESUMO

Kynurenic acid (KYNA) is derived from tryptophan, formed by the kynurenic pathway. KYNA is being widely studied as a biomarker for neurological and cardiovascular diseases, as it is found in ischemic conditions as a protective agent; however, little is known about its effect after ischemia-reperfusion in the vascular system. We induced ischemia for 30 min followed by 5 min reperfusion (I/R) in the rat aorta for KYNA evaluation using functional assays combined with proteomics. KYNA recovered the exacerbated contraction induced by phenylephrine and relaxation induced by acetylcholine or sodium nitroprussiate in the I/R aorta, with vessel responses returning to values observed without I/R. The functional recovery can be related to the antioxidant activity of KYNA, which may be acting on the endothelium-injury prevention, especially during reperfusion, and to proteins that regulate neurotransmission and cell repair/growth, expressed after the KYNA treatment. These proteins interacted in a network, confirming a protein profile expression for endothelium and neuron repair after I/R. Thus, the KYNA treatment had the ability to recover the functionality of injured ischemic-reperfusion aorta, by tissue repairing and control of neurotransmitter release, which reinforces its role in the post-ischemic condition, and can be useful in the treatment of such disease.


Assuntos
Aorta/patologia , Ácido Cinurênico/uso terapêutico , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/metabolismo , Proteômica , Acetilcolina/farmacologia , Animais , Aorta/efeitos dos fármacos , Aorta/fisiopatologia , Modelos Animais de Doenças , Ácido Cinurênico/farmacologia , Contração Miocárdica/efeitos dos fármacos , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Nitroprussiato/farmacologia , Fenilefrina/farmacologia , Mapas de Interação de Proteínas/efeitos dos fármacos , Ratos Sprague-Dawley , Vasodilatação/efeitos dos fármacos
9.
Medicine (Baltimore) ; 100(26): e26518, 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34190185

RESUMO

ABSTRACT: Bicuspid aortic valve (BAV) disease has significant gaps in its clinical management practices. To highlight the potential utility of advanced hemodynamic biomarkers in strengthening BAV assessment, we used 4-dimentional flow magnetic resonance imaging to investigate altered hemodynamics in the ascending aorta (AAo).A total of 32 healthy controls and 53 age-matched BAV patients underwent cardiac magnetic resonance imaging at 3T, with cine imaging and 4D-flow. Analysis planes were placed along 3D-segmented aortas at the left ventricular outflow tract (LVOT), sinuses of Valsalva, mid-ascending aorta (MAA), and proximal to the first aortic branch. Locations were analyzed for aortic diameter (normalized to body surface area), pressure drop (PD), viscous energy loss (EL), and wall shear stress (WSS) sub-vectors (axial wall shear stress, circumferential wall shear stress [WSSC], magnitude wall shear stress). Student's t tests, or non-parametric equivalents, compared parameters between cohorts. Univariable and multivariable analyses explored the associations of AAo diameter with hemodynamics within the BAV cohort.Compared to control cohort, BAV patients showed significantly greater PD (MAA: 9.5 ±â€Š8.0 vs 2.8 ±â€Š2.4 mm Hg; P < .01), EL (from LVOT-AA1: 7.39 ±â€Š4.57 mW vs 2.90 ±â€Š1.07 mW; P < .01), and WSSC (MAA: 0.3 ±â€Š0.1 vs 0.2 ±â€Š0.06 Pa; P ≤ .01) throughout the AAo. Correlational analyses revealed an inverse association between AAo diameter and both magnitude wall shear stress and axial wall shear stress.BAV patients exhibited increased PD, EL, and WSSC in the AAo, and an inverse association between AAo diameter and WSS sub-vectors. This demonstrated the impact of PD, EL, and WSS in BAV disease and the importance of altered hemodynamics in aortic remodelling.


Assuntos
Aorta , Valva Aórtica , Doença da Válvula Aórtica Bicúspide , Remodelação Vascular , Adulto , Aorta/diagnóstico por imagem , Aorta/patologia , Aorta/fisiopatologia , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/fisiopatologia , Pressão Arterial , Doença da Válvula Aórtica Bicúspide/diagnóstico , Doença da Válvula Aórtica Bicúspide/fisiopatologia , Velocidade do Fluxo Sanguíneo , Correlação de Dados , Feminino , Hemodinâmica , Humanos , Imagem Cinética por Ressonância Magnética/métodos , Masculino , Tamanho do Órgão , Resistência ao Cisalhamento
11.
J Surg Res ; 264: 544-552, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33864962

RESUMO

BACKGROUND: Conventional models of hypertrophic preconditioning (C-HP) can be established surgically through transverse aortic constriction (TAC) → deconstriction (De-TAC) → reconstriction (Re-TAC) characterized by dynamic afterload while it exerts technical difficulty on operators and poses high mortality during perioperative period in mice. We aimed to introduce an optimized method for obtaining a hypertrophic preconditioning (O-HP) model for further study on cardiac hypertrophy. METHODS: Ninety mice were divided into four groups: sham, TAC, C-HP, and O-HP. The sham group was exerted on three-time thoracotomies. The TAC group experienced twice thoracotomies and one TAC operation. C-HP and O-HP groups were given TAC, De-TAC, and Re-TAC operation at day 0, day 3, and day 7 in conventional and optimized method, respectively. We optimized the operating procedure in O-HP mice compared with the C-HP group by (1) leaving a ∼3-cm suture fixed in the subcutaneous layer after aortic constriction in TAC surgery (2) using two small forceps to untie the constriction knot instead of cutting it in the De-TAC operation. Ultrasound biomicroscopy was used for hemodynamics and cardiac function detection. Four weeks after the third surgery, all mice were sacrificed and pathology was analyzed among four groups. RESULTS: Four weeks after Re-TAC, the survival of O-HP mice was 63.3% while that of C-HP was 26.7%. Ultrasound biomicroscopy showed a successful establishment of HP models. C-HP and O-HP mice had improved cardiac structure and function indicated by left ventricular end-systolic diameter, left ventricular end-systolic posterior wall thickness, left ventricular ejection fraction, and left ventricular fractional shortening than the TAC group. Pathological analysis showed O-HP as well as C-HP had less hypertrophy than the TAC mice. CONCLUSIONS: Our results provide a rapid, safe, efficient, and reproducible method for optimized establishment of the HP model, which will facilitate studies for early intervention and prevention of left ventricular hypertrophy and heart failure.


Assuntos
Insuficiência Cardíaca/terapia , Hipertrofia Ventricular Esquerda/terapia , Animais , Aorta/fisiopatologia , Modelos Animais de Doenças , Estudos de Viabilidade , Insuficiência Cardíaca/fisiopatologia , Humanos , Hipertrofia Ventricular Esquerda/fisiopatologia , Masculino , Camundongos , Reprodutibilidade dos Testes , Volume Sistólico/fisiologia , Função Ventricular Esquerda/fisiologia
12.
Diab Vasc Dis Res ; 18(2): 14791641211011009, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33908285

RESUMO

INTRODUCTION: Increasing arterial stiffness is a feature of vascular aging that is accelerated by conditions that enhance cardiovascular risk, including diabetes mellitus. Multiple studies demonstrate divergence of carotid-femoral pulse wave velocity and augmentation index in persons with diabetes mellitus, though mechanisms responsible for this are unclear. MATERIALS AND METHODS: We tested the effect of acutely and independently increasing plasma glucose, plasma insulin, or both on hemodynamic function and markers of arterial stiffness (including carotid-femoral pulse wave velocity, augmentation index, forward and backward wave reflection amplitude, and wave reflection magnitude) in a four-arm, randomized study of healthy young adults. RESULTS: Carotid-femoral pulse wave velocity increased only during hyperglycemic-hyperinsulinemia (+0.36 m/s; p = 0.032), while other markers of arterial stiffness did not change (all p > 0.05). Heart rate (+3.62 bpm; p = 0.009), mean arterial pressure (+4.14 mmHg; p = 0.033), central diastolic blood pressure (+4.16 mmHg; p = 0.038), and peripheral diastolic blood pressure (+4.09 mmHg; p = 0.044) also significantly increased during hyperglycemic-hyperinsulinemia. CONCLUSIONS: Hyperglycemic-hyperinsulinemia acutely increased cfPWV, heart rate, mean arterial pressure, and diastolic blood pressure in healthy humans, perhaps reflecting enhanced sympathetic tone. Whether repeated bouts of hyperglycemia with hyperinsulinemia contribute to chronically-enhanced arterial stiffness remains unknown.


Assuntos
Aorta/fisiopatologia , Glicemia/metabolismo , Hiperglicemia/fisiopatologia , Hiperinsulinismo/fisiopatologia , Insulina/sangue , Rigidez Vascular , Adolescente , Adulto , Biomarcadores/sangue , Velocidade da Onda de Pulso Carótido-Femoral , Feminino , Humanos , Hiperglicemia/sangue , Hiperglicemia/diagnóstico , Hiperinsulinismo/sangue , Hiperinsulinismo/diagnóstico , Masculino , Fatores de Tempo , Virginia , Adulto Jovem
13.
Oxid Med Cell Longev ; 2021: 8865979, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33791074

RESUMO

Polycystic ovary syndrome (PCOS) is associated with elevated cardiovascular risk. Early vascular dysfunction may lead to the development of cardiovascular disease in PCOS. Vitamin D deficiency (VDD) is a common comorbidity of PCOS that contributes to the pathogenesis of the disease and its complications. Both PCOS and VDD are accompanied by increased oxidative stress that may be involved in the arising vascular dysfunction. We aimed to investigate the role of vitamin D status on aortic function. PCOS was induced by an 8-week-long transdermal testosterone treatment of female rats, and low and adequate vitamin D status was achieved by dietary means. Contraction and relaxation abilities of isolated aortic segments were measured by myograph. Resorcin-fuchsin staining and immunohistochemical labeling of 3-nitrotyrosine were performed. No difference was shown in the norepinephrine-induced contraction of the aortas of different groups, whereas we detected reduced acetylcholine- and insulin-evoked relaxation in VDD groups. A lower level of resorcin-fuchsin staining and elevated 3-nitrotyrosine immunostaining was observed in VDD. In our study, we demonstrated early endothelial dysfunction in VDD PCOS rat model. Vitamin D supplementation could prevent vascular disturbances, while VDD itself damaged endothelium-dependent vasorelaxation and induced nitrative stress.


Assuntos
Aorta/fisiopatologia , Síndrome do Ovário Policístico/fisiopatologia , Vitamina D/farmacologia , Animais , Aorta/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Contração Muscular/efeitos dos fármacos , Ratos Wistar , Coloração e Rotulagem
14.
Life Sci ; 278: 119560, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-33915131

RESUMO

AIMS: The structure-vasorelaxant activity relationships (SARs) assessment in previous study has found that trans-3,4,4'-trihydroxystilbene (344OH) could potentially act as a vasorelaxing agent with demonstration of over 2-fold maximal relaxation (Rmax) compared to its analogue, resveratrol. The present study focuses on the mechanism of actions and pathways employed by 344OH and compared to its analogue to further speculate the SAR of stilbenoids towards vasorelaxation. MATERIALS AND METHODS: The 344OH employed in present study was synthesized based on the protocol in previous study. The vascular responses towards the cumulative addition of 344OH were evaluated using in vitro rat aortic rings assays. KEY FINDINGS: The pEC50 and Rmax values were found to be 4.33 ± 0.05 and 106 ± 3.99%, respectively. Results showed that the vasorelaxation of 344OH were predominated by G-protein-coupled muscarinic- (M3) and ß2-adrenergic receptors, followed by PGI2/AC/cAMP- and NO/sGC/cGMP-dependent pathways. It was also identified that 344OH employed voltage-activated- (Kv), calcium-activated- (Kca) and inwardly-rectifying (Kir) potassium channels and act as an antagonist for both VOCC and IP3R while regulating the action potential in the vasculature. SIGNIFICANCE: The different position of hydroxyl substituent located in A-ring of the stilbenoid backbone in 344OH compared to resveratrol resulted in a significant difference in mechanistic actions that lead to 344OH's fast-acting and less time-dependent vasorelaxation behaviour. This has substantially increased the potential of 344OH to be developed as an effective antihypertensive drug in future. Present findings further strengthen our inferences where the SARs study approach should be carried out as the mainstream methodology in future drug development research.


Assuntos
Anti-Hipertensivos/farmacologia , Aorta/efeitos dos fármacos , Estilbenos/farmacologia , Vasodilatadores/farmacologia , Animais , Anti-Hipertensivos/química , Aorta/fisiopatologia , Descoberta de Drogas , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Masculino , Ratos Sprague-Dawley , Estilbenos/química , Vasodilatação/efeitos dos fármacos , Vasodilatadores/química
15.
Vasc Endovascular Surg ; 55(6): 541-543, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33813957

RESUMO

OBJECTIVE: The Society for Vascular Surgery stated there are a lack of studies describing long-term surveillance for aortobifemoral (AoBF) bypasses. Our goal was to investigate the value of DU studies as a surveillance tool for AoBF bypasses. METHODS: We retrospectively identified patients in our prospectively maintained database who underwent AoBF bypasses between 1995-2018. Surveillance was performed routinely with DU post-operatively, every 6 months for 1 year, and then annually. We considered "abnormal" DU findings to include peri-graft fluid, pseudoaneurysm or, peak systolic velocities (PSVs) > 350 cm/sec or PSV ratio > 3.5 anywhere from the proximal aortic to distal femoral anastomosis. If abnormalities were identified patients underwent intervention or shorter surveillance intervals. RESULTS: Of 153 AoBF bypasses, 60 patients with 120 graft limbs fulfilled our post-operative surveillance protocol with a mean follow-up of 4.0 years (0.5-24 years). "Normal" DU surveillance studies were documented throughout follow-up in 112 (93%) limbs. Of these, 2 (1.7%) developed acute limb occlusion. Eight (6.7%) limbs had "abnormal" DU findings: 5 failing grafts with focal elevated PSVs, 2 with peri-graft fluid leading to a diagnosis of an infected graft, and 1 with a pseudoaneurysm (PSA). Contrast arteriography or CT-angiography confirmed > 75% diameter stenosis, fluid or PSA in all 8 limbs. Graft revision (5 endovascular, 2 surgical) was performed in 7 of the 8 limbs initially or after 2 successive "abnormal" DU studies within 6 weeks of each other; 1 patient refused intervention. Without surveillance, urgent or emergent treatment might have proved necessary in 7.5% (7 + 2 = 9/120) of cases instead of only 1.7% (2/120) of cases. CONCLUSION: Vascular surgeons should adopt DU as a useful surveillance tool to identify AoBF bypasses that are failing or have other problems not identified clinically. Persistence of "abnormal" DU findings should prompt operative or endovascular intervention.


Assuntos
Aorta/cirurgia , Implante de Prótese Vascular/efeitos adversos , Artéria Femoral/cirurgia , Doença Arterial Periférica/cirurgia , Complicações Pós-Operatórias/diagnóstico por imagem , Falha de Prótese , Ultrassonografia Doppler Dupla , Aorta/diagnóstico por imagem , Aorta/fisiopatologia , Prótese Vascular , Implante de Prótese Vascular/instrumentação , Bases de Dados Factuais , Artéria Femoral/diagnóstico por imagem , Artéria Femoral/fisiopatologia , Humanos , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/fisiopatologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/fisiopatologia , Complicações Pós-Operatórias/cirurgia , Valor Preditivo dos Testes , Reoperação , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Grau de Desobstrução Vascular
16.
Am J Physiol Heart Circ Physiol ; 320(6): H2305-H2312, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33861146

RESUMO

Adults with metabolic syndrome (MetS) have increased fasting arterial stiffness and altered central hemodynamics that contribute, partly, to increased cardiovascular disease (CVD) risk. Although insulin affects aortic wave reflections in healthy adults, the effects in individuals with MetS are unclear. We hypothesized that insulin stimulation would reduce measures of pressure waveforms and hemodynamics in people with MetS. Thirty-five adults with obesity (27 women; 54.2 ± 6.0 yr; 37.1 ± 4.8 kg/m2) were selected for MetS (ATP III criteria) following an overnight fast. Pulse wave analysis was assessed using applanation tonometry before and after a 2-h euglycemic-hyperinsulinemic clamp (90 mg/dL, 40 mU/m2/min). Deconvolution analysis was used to decompose the aortic waveform [augmentation index corrected to heart rate of 75 beats/min (AIx@75); augmentation pressure (AP)] into backward and forward pressure components. Aerobic fitness (V̇o2max), body composition (DXA), and blood biochemistries were also assessed. Insulin significantly reduced augmentation index (AIx@75, 28.0 ± 9.6 vs. 23.0 ± 9.9%, P < 0.01), augmentation pressure (14.8 ± 6.4 vs. 12.0 ± 5.7 mmHg, P < 0.01), pulse pressure amplification (1.26 ± 0.01 vs. 0.03 ± 0.01, P = 0.01), and inflammation [high-sensitivity C-reactive protein (hsCRP): P = 0.02; matrix metallopeptidase 7 (MMP-7): P = 0.03] compared to fasting. In subgroup analyses to understand HTN influence, there were no insulin stimulation differences on any outcome. V̇o2max, visceral fat, and blood potassium correlated with fasting AIx@75 (r = -0.39, P = 0.02; r = 0.41, P = 0.03; r = -0.53, P = 0.002). Potassium levels were also associated with insulin-mediated reductions in AP (r = 0.52, P = 0.002). Our results suggest insulin stimulation improves indices of aortic reflection in adults with MetS.NEW & NOTEWORTHY This study is one of the first to investigate the effects of insulin on central and peripheral hemodynamics in adults with metabolic syndrome. We provide evidence that insulin infusion reduces aortic wave reflection, potentially through a reduction in inflammation and/or via a potassium-mediated vascular response.


Assuntos
Aorta/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Insulina/farmacologia , Síndrome Metabólica/fisiopatologia , Análise de Onda de Pulso , Rigidez Vascular/efeitos dos fármacos , Aorta/fisiopatologia , Composição Corporal , Aptidão Cardiorrespiratória , Feminino , Técnica Clamp de Glucose , Hemodinâmica/efeitos dos fármacos , Humanos , Resistência à Insulina , Masculino , Síndrome Metabólica/metabolismo , Pessoa de Meia-Idade , Consumo de Oxigênio , Rigidez Vascular/fisiologia
17.
Am J Physiol Heart Circ Physiol ; 320(6): H2270-H2282, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33834870

RESUMO

Despite a decline in popularity over the past several decades, cigarette smoking remains a leading cause of cardiovascular morbidity and mortality. Yet, the effects of cigarette smoking on vascular structure and function are largely unknown. To evaluate changes in the mechanical properties of the aorta that occur with chronic smoking, we exposed female apolipoprotein E-deficient mice to mainstream cigarette smoke daily for 24 wk, with room air as control. By the time of euthanasia, cigarette-exposed mice had lower body mass but experienced larger systolic/diastolic blood pressure when compared with controls. Smoking was associated with significant wall thickening, reduced axial stretch, and circumferential material softening of the aorta. Although this contributed to maintaining intrinsic tissue stiffness at control levels despite larger pressure loads, the structural stiffness became significantly larger. Furthermore, the aorta from cigarette-exposed mice exhibited decreased ability to store elastic energy and augment diastolic blood flow. Histological analysis revealed a region-dependent increase in the cross-sectional area due to smoking. Increased smooth muscle and extracellular matrix content led to medial thickening in the ascending aorta, whereas collagen deposition increased the thickness of the descending thoracic and abdominal aorta. Atherosclerotic lesions were larger in exposed vessels and featured a necrotic core overlaid by a thinned fibrous cap and macrophage infiltration, consistent with a vulnerable phenotype. Collectively, our data indicate that cigarette smoking decreases the mechanical functionality of the aorta, inflicts morphometric alterations to distinct segments of the aorta, and accelerates the progression of atherosclerosis.NEW & NOTEWORTHY We studied the effects of chronic cigarette smoking on the structure and function of the aorta in a mouse model of nose-only aerosol inhalation. Our data indicated that exposure to cigarette smoke impairs vascular function by reducing the ability of the aorta to store elastic energy and by decreasing aortic distensibility. Combined with a more vulnerable atherosclerotic phenotype, these findings reveal the biomechanical mechanisms that support the development of cardiovascular disease due to cigarette smoking.


Assuntos
Aorta/metabolismo , Fumar Cigarros/metabolismo , Matriz Extracelular/metabolismo , Músculo Liso Vascular/metabolismo , Remodelação Vascular , Animais , Aorta/patologia , Aorta/fisiopatologia , Fenômenos Biomecânicos , Fumar Cigarros/patologia , Fumar Cigarros/fisiopatologia , Modelos Animais de Doenças , Matriz Extracelular/patologia , Matriz Extracelular/fisiologia , Feminino , Interação Gene-Ambiente , Camundongos , Camundongos Knockout para ApoE , Músculo Liso Vascular/patologia , Músculo Liso Vascular/fisiopatologia , Fumaça
18.
Ultrasound Med Biol ; 47(7): 1725-1736, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33858722

RESUMO

The conventional manual approach to measurement of aortic pulse wave velocity (PWV) by Doppler ultrasonography is time consuming and operator dependent. Here we report a new semi-automated methodology for more efficient and objective measurement of aortic PWV and results of tests of its clinical feasibility and reproducibility. Carotid-femoral pulse wave velocity (cfPWV) was measured in 50 patients with suspected coronary artery disease (aged 59.2 ± 10.0 y, 36 males) by three independent observers, including two experienced sonographers and one cardiologist without ultrasonographic experience. The cfPWV measured by the semi-automatic method (cfPWVA) was compared with reference values obtained by averaging measurements by two experienced sonographers using the conventional standard manual method (cfPWVM). Measurements of cfPWVA were feasible in all 50 patients and exhibited excellent agreement with averaged cfPWVM from the two experienced sonographers, with an intraclass correlation coefficient (ICC) of 0.915 (95% confidence interval: 0.876-0.942). The inexperienced observer-measured cfPWVA did not differ from the cfPWVM measured by the two experienced sonographers (8.04 ± 1.29 vs. 8.14 ± 1.32 m/s, p > 0.05), with a high consistency by ICC of 0.877 (0.793-0.928). Bland-Altman plots further illustrated the good agreement between the two methods and good intra- and inter-observer reproducibility. Time consumption for cfPWV measurement using the new method was significantly less than that for the manual method (122 ± 35 s vs. 455 ± 105 s, p < 0.0001), saving about 73% of the time. This new semi-automatic methodology for aortic PWV measurement not only has an accuracy similar to that of the conventional standard manual method but is also highly feasible and time saving. It may provide a reliable, simple and reproducible approach to arterial stiffness evaluation in clinical settings.


Assuntos
Aorta/diagnóstico por imagem , Aorta/fisiopatologia , Análise de Onda de Pulso , Ultrassonografia Doppler/métodos , Rigidez Vascular , Idoso , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes
20.
Sci Rep ; 11(1): 6052, 2021 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-33723367

RESUMO

Type 2 diabetes (T2D) is associated with cardiovascular and pulmonary disease. How T2D affects pulmonary endothelial function is not well characterized. We investigated the effects of T2D progression on contractility machinery and endothelial function in the pulmonary and systemic circulation and the mechanisms promoting the dysfunction, using pulmonary artery (PA) and aorta. A high-fat (HF, 3 weeks 60% lipid-rich diet) and a high-fat/high-sucrose (HFHSu, combined 60% lipid-rich diet and 35% sucrose during 25 weeks) groups were used as prediabetes and T2D rat models. We found that T2D progression differently affects endothelial function and vascular contractility in the aorta and PA, with the contractile machinery being altered in the PA and aorta in prediabetes and T2D animals; and endothelial function being affected in both models in the aorta but only affected in the PA of T2D animals, meaning that PA is more resistant than aorta to endothelial dysfunction. Additionally, PA and systemic endothelial dysfunction in diabetic rats were associated with alterations in the nitrergic system and inflammatory pathways. PA dysfunction in T2D involves endothelial wall mineralization. The understanding of the mechanisms behind PA dysfunction in T2D can lead to significant advances in both preventative and therapeutic treatments of pulmonary disease-associated diabetes.


Assuntos
Aorta , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Endotélio Vascular , Artéria Pulmonar , Vasoconstrição , Animais , Aorta/metabolismo , Aorta/patologia , Aorta/fisiopatologia , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Experimental/fisiopatologia , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Diabetes Mellitus Tipo 2/fisiopatologia , Endotélio Vascular/metabolismo , Endotélio Vascular/patologia , Endotélio Vascular/fisiopatologia , Masculino , Artéria Pulmonar/metabolismo , Artéria Pulmonar/patologia , Artéria Pulmonar/fisiopatologia , Ratos , Ratos Wistar
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