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1.
Nat Rev Cardiol ; 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31570832

RESUMO

The first issue of Nature Reviews Cardiology was published in November 2004 under the name Nature Clinical Practice Cardiovascular Medicine. To celebrate our 15th anniversary in 2019, we invited six of our Advisory Board members to discuss what they considered the most important advances in their field of cardiovascular research or clinical practice in the past 15 years and what changes they envision for cardiovascular medicine in the next 15 years. Several practice-changing breakthroughs are described, including advances in procedural techniques to treat arrhythmias and hypertension and the development of novel therapeutic strategies to treat heart failure and pulmonary arterial hypertension, as well as those that target risk factors such as inflammation and elevated LDL-cholesterol levels. Furthermore, these key opinion leaders predict that machine learning technology and data derived from wearable devices will pave the way towards the coveted goal of personalized medicine.

2.
Clin Res Cardiol ; 2019 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-31144065

RESUMO

BACKGROUND: Extracellular nucleotide metabolism contributes to chronic inflammation, cell differentiation, and tissue mineralization by controlling nucleotide and adenosine concentrations and hence its purinergic effects. This study investigated location-specific changes of extracellular nucleotide metabolism in aortic valves of patients with calcific aortic valve disease (CAVD). Individual ecto-enzymes and adenosine receptors involved were analyzed together with correlation with CAVD severity and risk factors. RESULTS: Nucleotide and adenosine degradation rates were adversely modified on the aortic surface of stenotic valve as compared to ventricular side, including decreased ATP removal (1.25 ± 0.35 vs. 2.24 ± 0.61 nmol/min/cm2) and adenosine production (1.32 ± 0.12 vs. 2.49 ± 0.28 nmol/min/cm2) as well as increased adenosine deamination (1.28 ± 0.31 vs. 0.67 ± 0.11 nmol/min/cm2). The rates of nucleotide to adenosine conversions were lower, while adenosine deamination was higher on the aortic sides of stenotic vs. non-stenotic valve. There were no differences in extracellular nucleotide metabolism between aortic and ventricular sides of non-stenotic valves. Furthermore, nucleotide degradation rates, measured on aortic side in CAVD (n = 62), negatively correlated with echocardiographic and biochemical parameters of disease severity (aortic jet velocity vs. ATP hydrolysis: r = - 0.30, p < 0.05; vs. AMP hydrolysis: r = - 0.44, p < 0.001; valvular phosphate concentration vs. ATP hydrolysis: r = - 0.26, p < 0.05; vs. AMP hydrolysis: r = - 0.25, p = 0.05) while adenosine deamination showed positive correlation trend with valvular phosphate deposits (r = 0.23, p = 0.07). Nucleotide and adenosine conversion rates also correlated with CAVD risk factors, including hyperlipidemia (AMP hydrolysis vs. serum LDL cholesterol: r = - 0.28, p = 0.05; adenosine deamination vs. total cholesterol: r = 0.25, p = 0.05; LDL cholesterol: r = 0.28, p < 0.05; triglycerides: r = 0.32, p < 0.05), hypertension (adenosine deamination vs. systolic blood pressure: r = 0.28, p < 0.05) and thrombosis (ATP hydrolysis vs. prothrombin time: r = - 0.35, p < 0.01). Functional assays as well as histological and immunofluorescence, flow cytometry and RT-PCR studies identified all major ecto-enzymes engaged in nucleotide metabolism in aortic valves that included ecto-nucleotidases, alkaline phosphatase, and ecto-adenosine deaminase. We have shown that changes in nucleotide-converting ecto-enzymes were derived from their altered activities on valve cells and immune cell infiltrate. We have also demonstrated a presence of A1, A2a and A2b adenosine receptors with diminished expression of A2a and A2b in stenotic vs. non-stenotic valves. Finally, we revealed that augmenting adenosine effects by blocking adenosine deamination with deoxycoformycin decreased aortic valve thickness and reduced markers of calcification via adenosine-dependent pathways in a mouse model of CAVD. CONCLUSIONS: This work highlights profound changes in extracellular nucleotide and adenosine metabolism in CAVD. Altered extracellular nucleotide hydrolysis and degradation of adenosine in stenotic valves may affect purinergic responses to support a pro-stenotic milieu and valve calcification. This emphasizes a potential mechanism and target for prevention and therapy. .

3.
Drug Dev Ind Pharm ; 45(7): 1149-1156, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31007093

RESUMO

Dry powder inhalers (DPIs) are considered a main drug delivery system through pulmonary route. The main objective of this work is to study the flow of differently shaped microparticles in order to find the optimum shape of drug particles that will demonstrate the best flow to the deep lung. The flowability of particles in air or any fluid depends particularly on the drag force which is defined as the resistance of the fluid molecules to the particle flow. One of the most important parameters that affect the drag force is the particles' shape. Computational simulations using COMSOL Multi Physics 5.2 software were performed for investigating the particles flow in the air pathways of lung, and the drag force was calculated for different particles shapes. This was accomplished by screening a set of 17 possible shapes that are expected to be synthesized easily in the micro-scale. In addition, the macro-scale behavior of the investigated shapes was also simulated so as to compare the behavior of the flowing particles in both cases. A very big difference was found between the behavior of particles' flow in the micro and macro scales, but a similar behavior can be obtained if the flow velocity of the microparticles is very high. It was also found that the micro-triangle with aspect ratio 2:1 has the least drag force in both deep and upper lung; so, it should be the shape of choice during the process of particle synthesis for pulmonary drug delivery.

4.
Ann Thorac Surg ; 108(1): e25-e28, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30576634

RESUMO

Anomalous origin of the left main coronary artery from the right coronary sinus is associated with sudden cardiac death. We present a young adult who was diagnosed with this anomaly after an aborted sudden cardiac death. He underwent a complete anatomical repair by translocating the left coronary artery to the left coronary sinus of Valsalva, with excellent 10 years outcome.


Assuntos
Anomalias dos Vasos Coronários/cirurgia , Vasos Coronários/cirurgia , Morte Súbita Cardíaca/etiologia , Adulto , Humanos , Masculino
5.
J Am Coll Cardiol ; 72(22): 2761-2777, 2018 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-30497563

RESUMO

The ideal aortic valve substitute for young and middle-aged adults remains elusive. The Ross procedure (pulmonary autograft replacement) is the only operation that allows replacement of the diseased aortic valve with a living substitute. However, use of this procedure has declined significantly due to concerns over increased surgical risk and potential long-term failure of the operation. Several recent publications from expert centers have shown that in the current era, the Ross procedure can be performed safely and reproducibly in appropriately selected patients. Furthermore, an increasing body of evidence suggests that the Ross procedure is associated with better long-term outcomes compared with conventional aortic valve replacement in young and middle-aged adults. In this paper, the authors review the indications and technical considerations of the Ross procedure, describe its advantages and drawbacks, and discuss patient selection criteria. Finally, the authors provide a comprehensive synthesis of the current Ross published reports to enable cardiologists and surgeons to make appropriate decisions for their patients with aortic valve disease.

6.
Nat Rev Cardiol ; 15(12): 770-779, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30367136

RESUMO

The epidemics of heart failure and, to a lesser extent, of pulmonary arterial hypertension continue unabated worldwide and are extremely costly in terms of loss of life and earnings, as well as the burden of health-care expenditure due to repeated hospitalization. The effectiveness of newly discovered therapies for the two conditions depends on their timely application. To date, symptoms have been used to guide the application and timing of therapy. Compelling evidence now exists that symptoms are preceded by several metabolic and haemodynamic changes, particularly a rise in intravascular pressures during exercise. These observations have stimulated the development of several implantable devices for the detection of impending unstable heart failure or pulmonary arterial hypertension, necessitating admission to hospital. In this Review, we summarize the rationale for monitoring patients with heart failure or pulmonary arterial hypertension, the transition from noninvasive to implantable devices and the current and anticipated clinical uses of these devices.

7.
J Am Coll Cardiol ; 72(12): 1397-1416, 2018 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-30213333

RESUMO

Rheumatic heart disease (RHD) is a preventable heart condition that remains endemic among vulnerable groups in many countries. After a period of relative neglect, there has been a resurging interest in RHD worldwide over the past decade. In this Scientific Expert Panel, the authors summarize recent advances in the science of RHD and sketch out priorities for current action and future research. Key questions for laboratory research into disease pathogenesis and epidemiological research on the burden of disease are identified. The authors present a variety of pressing clinical research questions on optimal RHD prevention and advanced care. In addition, they propose a policy and implementation research agenda that can help translate current evidence into tangible action. The authors maintain that, despite knowledge gaps, there is sufficient evidence for national and global action on RHD, and they argue that RHD is a model for strengthening health systems to address other cardiovascular diseases in limited-resource countries.

8.
Int J Cardiol ; 273: 155-161, 2018 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-30213605

RESUMO

BACKGROUND: Whether early vs. delayed referral to septal reduction therapies (SRT, alcohol septal ablation or surgical myectomy) bears prognostic relevance in hypertrophic obstructive cardiomyopathy (HOCM) is unresolved. We analyzed the impact of SRT timing on the outcome of HOCM patients. METHODS: We followed 126 patients for 5 ±â€¯4 years after SRT (mean age 53 ±â€¯15 years; 55 post-ASA and 71 post-SM). Based on time-to-treatment (TTT; from HOCM diagnosis to SRT), patients were divided into three groups: "<3" years, N = 50; "3-5" years, N = 25; ">5" years, N = 51. RESULTS: Patients with TTT > 5 years were younger at diagnosis and more often had atrial fibrillation (AF). Left ventricular outflow tract (LVOT) gradients were comparable in the 3 TTT groups. Two patients died peri-operatively, all with TTT > 5. Long-term, 8 patients died (3 suddenly and 5 due to heart failure). Mortality increased progressively with TTT (2% vs. 4% vs. 12% for TTT "<3", "3-5", and ">5" years, p for trend = 0.039). Independent predictors of disease progression (new-onset AF, worsening to NYHA III/IV symptoms, re-intervention or death) were TTT ("3-5" vs. "<3" years: HR: 4.988, 95%CI: 1.394-17.843; ">5" vs. "<3" years: HR: 3.420, 95%CI: 1.258-9.293, overall p-value = 0.025), AF at baseline (HR: 1.896, 95%CI: 1.002-3.589, p = 0.036) and LVOT gradient (HR per mm Hg increase: 1.022, 95%CI: 1.007-1.024, p = 0.023). CONCLUSIONS: Delay in SRT referral has significant impact on long-term outcome of patients with HOCM, particularly when >5 years from first detection of gradient, even when successful relief of symptoms and gradient is achieved. Earlier interventions are associated with lower complication rates and better prognosis, suggesting the importance of timely SRT to maximize treatment benefit and prevent late HOCM-related complications.

14.
Cardiovasc J Afr ; 29(4): 256-259, 2018 Jul/Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-30080213

RESUMO

Mission: to urge all relevant entities within the international cardiac surgery, industry and government sectors to commit to develop and implement an effective strategy to address the scourge of rheumatic heart disease in the developing world through increased access to life-saving cardiac surgery.

15.
Cardiovasc Pathol ; 36: 53-63, 2018 Sep - Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30056298

RESUMO

BACKGROUND: The calcific aortic valve disease (CAVD) is a common heart pathology that involves inflammation, fibrosis, and calcification of aortic valve leaflets. All these processes could be affected by changes in the extracellular purinergic signaling that depend on the activity of ectonucleotidases, mainly ectonucleoside triphosphate diphosphohydrolase 1 (CD39, eNTPD1) and ecto-5'nucleotidase (CD73, e5NT). OBJECTIVE AND METHODS: We investigated the localization of CD39 and CD73 proteins in human noncalcified and calcified aortic valves using immunohistochemistry together with analysis of NTPDases and e5NT activities in aortic valve homogenates by analysis of substrate into product conversion by high-performance liquid chromatography. We also measured the rates of extracellular nucleotide catabolism on the surface of isolated cultured aortic valve endothelial (hAVECs) and interstitial cells (hAVICs) as well as characterized cellular CD39 and CD73 distribution. RESULTS: In noncalcified valves, CD39 and CD73 were expressed in both endothelial and interstitial cells, while in calcified valves, the expressions of CD39 and CD73 were significantly down-regulated with the exception of calcified regions where the expression of CD73 was maintained. This correlated with activities in valve homogenates. NTPDase was reduced by 35% and e5NT activity by 50% in calcified vs. noncalcified valve. CD39 and CD73 were present mainly in the cell membrane of hAVECs, but in hAVICs, these proteins were also present intracellularly. The rates of extracellular adenosine triphosphate and adenosine monophosphate hydrolysis in isolated hAVECs and hAVICs were comparable. CONCLUSION: The presence of ectonucleotidases in valves and especially in aortic valve interstitial cells highlights important local role of purinergic signaling and metabolism. Changes in the local expression and hence the activity of CD39 and CD73 in calcified valves suggest their potential role in CAVD.

16.
J Thorac Cardiovasc Surg ; 156(3): 951-962.e2, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29884493

RESUMO

OBJECTIVES: Valve-conserving operations for aneurysms of the ascending aorta and root offer many advantages, and their use is steadily increasing. Optimizing the results of these operations depends on providing the best conditions for normal function and durability of the new root. METHODS: Multimodality imaging including 2-dimensional echocardiography, multislice computed tomography, and cardiovascular magnetic resonance combined with image processing and computational fluid dynamics were used to define geometry, dynamism and aortic root function, before and after the remodeling operation. This was compared with 4 age-matched controls. RESULTS: The size and shape of the ascending aorta, aortic root, and its component parts showed considerable changes postoperatively, with preservation of dynamism. The postoperative size of the aortic annulus was reduced without the use of external bands or foreign material. Importantly, the elliptical shape of the annulus was maintained and changed during the cardiac cycle (Δ ellipticity index was 15% and 28% in patients 1 and 2, respectively). The "cyclic" area of the annulus changed in size (Δarea: 11.3% in patient 1 and 13.1% in patient 2). Functional analysis showed preserved reservoir function of the aortic root, and computational fluid dynamics demonstrated normalized pattern of flow in the ascending aorta, sinuses of Valsalva, and distal aorta. CONCLUSIONS: The remodeling operation results in near-normal geometry of the aortic root while maintaining dynamism of the aortic root and its components. This could have very important functional implications; the influence of these effects on both early- and long-term outcomes needs to be studied further.

17.
Cardiovasc Eng Technol ; 9(2): 151-157, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27709350

RESUMO

Responses of valve endothelial cells (VECs) to shear stresses are important for the regulation of valve durability. However, the effect of flow patterns subjected to VECs on the opposite surfaces of the valves on the production of extracellular matrix (ECM) has not yet been investigated. This study aims to investigate the response of side-specific flow patterns, in terms of ECM synthesis and/or degradation in porcine aortic valves. Aortic and ventricular sides of aortic valve leaflets were exposed to oscillatory and laminar flow generated by a Cone-and-Plate machine for 48 h. The amount of collagen, GAGs and elastin was quantified and compared to samples collected from the same leaflets without exposing to flow. The results demonstrated that flow is important to maintain the amount of GAGs and elastin in the valve, as compared to the effect of static conditions. Particularly, the laminar waveform plays a crucial role on the modulation of elastin in side-independent manner. Furthermore, the ability of oscillatory flow on the aortic surface to increase the amount of collagen and GAGs cannot be replicated by exposure of an identical flow pattern on the ventricular side of the valve. Side-specific responses to the particular patterns of flow are important to the regulation of ECM components. Such understanding is imperative to the creation of tissue-engineered heart valves that must be created from the "appropriate" cells that can replicate the functions of the native VECs to regulate the different constituents of ECM.

18.
Tissue Eng Part A ; 24(1-2): 145-156, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28467727

RESUMO

The ability of cells to secrete extracellular matrix proteins is an important property in the repair, replacement, and regeneration of living tissue. Cells that populate tissue-engineered constructs need to be able to emulate these functions. The motifs, KTTKS or palmitoyl-KTTKS (peptide amphiphile), have been shown to stimulate production of collagen and fibronectin in differentiated cells. Molecular modeling was used to design different forms of active peptide motifs to enhance the efficacy of peptides to increase collagen and fibronectin production using terminals KTTKS/SKTTK/SKTTKS connected by various hydrophobic linkers, V4A3/V4A2/A4G3. Molecular dynamic simulations showed SKTTKS-V4A3-SKTTKS (P3), with palindromic (SKTTKS) motifs and SKTTK-V4A2-KTTKS (P5), maintained structural integrity and favorable surface electrostatic distributions that are required for functionality. In vitro studies showed that peptides, P3 and P5, showed low toxicity to human adipose-derived stem cells (hADSCs) and significantly increased the production of collagen and fibronectin in a concentration-dependent manner compared with the original active peptide motif. The 4-day treatment showed that stem cell markers of hADSCs remained stable with P3. The molecular design of novel peptides is a promising strategy for the development of intelligent biomaterials to guide stem cell function for tissue engineering applications.


Assuntos
Matriz Extracelular/metabolismo , Células-Tronco/citologia , Células-Tronco/metabolismo , Engenharia Tecidual/métodos , Células Cultivadas , Colágeno/química , Fibronectinas/química , Citometria de Fluxo , Humanos , Peptídeos
19.
Sci Adv ; 3(12): e1701156, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29226241

RESUMO

Medial calcification in the human aorta accumulates during aging and is known to be aggravated in several diseases. Atherosclerosis, another major cause of cardiovascular calcification, shares some common aggravators. However, the mechanisms of cardiovascular calcification remain poorly understood. To elucidate the relationship between medial aortic calcification and atherosclerosis, we characterized the cross-sectional distributions of the predominant minerals in aortic tissue, apatite and whitlockite, and the associated extracellular matrix. We also compared the cellular changes between atherosclerotic and nonatherosclerotic human aortic tissues. This was achieved through the development of Raman spectroscopy imaging methods that adapted algorithms to distinguish between the major biomolecules present within these tissues. We present a relationship between apatite, cholesterol, and triglyceride in atherosclerosis, with the relative amount of all molecules concurrently increased in the atherosclerotic plaque. Further, the increase in apatite was disproportionately large in relation to whitlockite in the aortic media directly underlying a plaque, indicating that apatite is more pathologically significant in atherosclerosis-aggravated medial calcification. We also discovered a reduction of ß-carotene in the whole aortic intima, including a plaque in atherosclerotic aortic tissues compared to nonatherosclerotic tissues. This unprecedented biomolecular characterization of the aortic tissue furthers our understanding of pathological and physiological cardiovascular calcification events in humans.

20.
ACS Appl Mater Interfaces ; 9(50): 43520-43528, 2017 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-29182298

RESUMO

Representative compounds from three classes of microporous solids, namely, metal-organic frameworks (MOFs), hybrid ultra-microporous materials (HUMs), and porous-organic polymers (POPs), were investigated for their nitric oxide gas uptake and release behavior. Low-pressure sorption studies indicated strong chemisorption of NO on the free amine groups decorating the MOF UiO-66-NH2 when compared to its non-amine-functionalized parent. The HUMs demonstrated reversible physisorption within the low-pressure regime, but interestingly in one case there was evidence for chemisorption following pressurization with NO at 10 bar. Significant release of chemisorbed NO from the UiO-66-NH2 and one of the HUMs was triggered by addition of acid to the medium, a pH change from 7.4 to 5.4 being sufficient to trigger NO release. An imidazole-based POP exhibited chemisorption of NO at high pressure wherein the ring basicity facilitated both NO uptake and spontaneous release upon contact with the aqueous release medium.

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