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1.
Heart Lung Circ ; 28(9): 1310-1319, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31266725

RESUMO

Degenerative or fibrocalcific aortic stenosis (AS) is now the most common native valvular heart disease assessed and managed by cardiologists in developed countries. Transthoracic echocardiography remains the quintessential imaging modality for the non-invasive characterisation of AS due to its widespread availability, superior assessment of flow haemodynamics, and a wealth of prognostic data accumulated over decades of clinical utility and research applications. With expanding technologies and increasing availability of treatment options such as transcatheter aortic valve replacements, in addition to conventional surgical approaches, accurate and precise assessment of AS severity is critical to guide decisions for and timing of interventions. Despite clear guideline echocardiographic parameters demarcating severe AS, discrepancies between transvalvular velocities, gradients, and calculated valve areas are commonly encountered in clinical practice. This often results in diagnostically challenging cases with significant implications. Greater emphasis must be placed on the quality of performance of basic two dimensional (2D) and Doppler measurements (attention to detail ensuring accuracy and precision), incorporating ancillary haemodynamic surrogates, understanding study- or patient-specific confounders, and recognising the role and limitations of stress echocardiography in the subgroups of low-flow low-gradient AS. A multiparametric approach, along with the incorporation of multimodality imaging (cardiac computed tomography or magnetic resonance imaging) in certain scenarios, is now mandatory to avoid incorrect misclassification of severe AS. This is essential to ensure appropriate selection of patients who would most benefit from interventions on the aortic valve to relieve the afterload mismatch resulting from truly severe valvular stenosis.


Assuntos
Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/fisiopatologia , Valva Aórtica/patologia , Calcinose/diagnóstico por imagem , Calcinose/fisiopatologia , Ecocardiografia sob Estresse , Ecocardiografia , Hemodinâmica , Imagem Multimodal , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/fisiopatologia , Estenose da Valva Aórtica/prevenção & controle , Estenose da Valva Aórtica/terapia , Calcinose/prevenção & controle , Calcinose/terapia , Humanos , Substituição da Valva Aórtica Transcateter
2.
Int J Mol Sci ; 20(14)2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31340541

RESUMO

Apoptotic cell death is usually a response to the cell's microenvironment. In the kidney, apoptosis contributes to parenchymal cell loss in the course of acute and chronic renal injury, but does not trigger an inflammatory response. What distinguishes necrosis from apoptosis is the rupture of the plasma membrane, so necrotic cell death is accompanied by the release of unprocessed intracellular content, including cellular organelles, which are highly immunogenic proteins. The relative contribution of apoptosis and necrosis to injury varies, depending on the severity of the insult. Regulated cell death may result from immunologically silent apoptosis or from immunogenic necrosis. Recent advances have enhanced the most revolutionary concept of regulated necrosis. Several modalities of regulated necrosis have been described, such as necroptosis, ferroptosis, pyroptosis, and mitochondrial permeability transition-dependent regulated necrosis. We review the different modalities of apoptosis, necrosis, and regulated necrosis in kidney injury, focusing particularly on evidence implicating cell death in ectopic renal calcification. We also review the evidence for the role of cell death in kidney injury, which may pave the way for new therapeutic opportunities.


Assuntos
Lesão Renal Aguda/metabolismo , Proteínas Reguladoras de Apoptose/genética , Calcinose/metabolismo , Células Epiteliais/metabolismo , Rim/metabolismo , Necrose/metabolismo , Traumatismo por Reperfusão/metabolismo , Lesão Renal Aguda/tratamento farmacológico , Lesão Renal Aguda/genética , Lesão Renal Aguda/patologia , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Proteínas Reguladoras de Apoptose/classificação , Proteínas Reguladoras de Apoptose/metabolismo , Calcinose/genética , Calcinose/patologia , Calcinose/prevenção & controle , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , /genética , Regulação da Expressão Gênica , Humanos , /genética , Rim/efeitos dos fármacos , Rim/patologia , /genética , /genética , Necrose/genética , Necrose/patologia , Necrose/prevenção & controle , Substâncias Protetoras/farmacologia , Piroptose/efeitos dos fármacos , Piroptose/genética , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/patologia
3.
Kidney Blood Press Res ; 44(2): 188-199, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31067546

RESUMO

BACKGROUND: Cardiovascular disease is the leading cause of death in patients with chronic kidney disease (CKD) and metabolic acidosis might accelerate vascular calcification. The T50 calcification inhibition test (T50-test) is a global functional test analyzing the overall propensity of calcification in serum, and low T50-time is associated with progressive aortic stiffening and with all-cause mortality in non-dialysis CKD, dialysis, and transplant patients. Low serum bicarbonate is associated with a short T50-time and alkali supplementation could be a simple modifier of calcification propensity. The aim of this study was to investigate the short-term effect of oral sodium bicarbonate supplementation on T50-time in CKD patients. MATERIAL AND METHODS: The SoBic-study is an ongoing randomized-controlled trial in CKD-G3 and G4 patients with chronic metabolic acidosis (serum HCO3- ≤21 mmol/L), in which patients are randomized to either achieve serum HCO3- levels of 24 ± 1 mmol/L (intervention group) or 20 ± 1 mmol/L (rescue group). The effect of bicarbonate treatment on T50-time was assessed. RESULTS: The study cohort consisted of 35 (14 female) patients aged 57 (±15) years, and 18 were randomized to the intervention group. The mean T50-time was 275 (± 64) min. After 4 weeks, the mean change of T50-time was 4 (±69) min in the intervention group and 18 min (±56) in the rescue group (ß = -25; 95% CI: -71 to 22; p = 0.298). Moreover, change of serum bicarbonate in individual patients was not associated with change in T50-time, analyzed by regression analysis. Change of serum phosphate had a significant impact on change of T50-time (ß = -145; 95% CI: -237 to -52). CONCLUSION: Oral sodium bicarbonate supplementation showed no effect on T50-time in acidotic CKD patients.


Assuntos
Acidose/tratamento farmacológico , Calcinose/prevenção & controle , Insuficiência Renal Crônica/tratamento farmacológico , Bicarbonato de Sódio/administração & dosagem , Adulto , Idoso , Calcinose/sangue , Calcinose/tratamento farmacológico , Suplementos Nutricionais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Bicarbonato de Sódio/farmacologia , Bicarbonato de Sódio/uso terapêutico , Rigidez Vascular/efeitos dos fármacos
4.
Phytother Res ; 33(6): 1717-1725, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31016813

RESUMO

Inflammation is considered to be one of the initial critical factors in the occurrence of calcific heart valve disease. This study was to prove Nobiletin (NBT) inhibits inflammation-caused calcification of human valve interstitial cells (hVICs) and to elucidate the involved molecular mechanisms. Tumor necrosis factor-alpha (TNF-α)-induced hVICs were treated with or without NBT. Cell growth and calcification of hVICs were assessed. RNA sequencing was utilized to investigate the gene expression changes. Molecular target prediction and docking assay were further performed. NBT interfered with hVIC growth under TNF-α condition in a dose-dependent manner also presented a gradual decrease of positive Alizarin Red S staining, down-regulation of BMP2, and RUNX2 gene expression. Based on the global gene expression cluster, control and TNF-α plus NBT group showed a high similarity versus TNF-α only group. After Venn interaction of differential expression genes (DEGs), 2,236 common DEGs were identified to display different biological functions and signaling pathways. ABCG2 and AKR1B1 were further selected as prediction targets of NBT involved in RELA, TNF, BMP2, RUNX2, etc. interactions in mediating hVIC calcification. The results show that NBT is a natural product to prevent the occurrence of heart valve calcification.


Assuntos
Estenose da Valva Aórtica/prevenção & controle , Valva Aórtica/efeitos dos fármacos , Valva Aórtica/patologia , Calcinose/prevenção & controle , Flavonas/farmacologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Adulto , Aldeído Redutase/genética , Aldeído Redutase/metabolismo , Valva Aórtica/metabolismo , Estenose da Valva Aórtica/genética , Estenose da Valva Aórtica/metabolismo , Estenose da Valva Aórtica/patologia , Calcinose/genética , Calcinose/metabolismo , Calcinose/patologia , Células Cultivadas , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Feminino , Flavonas/química , Regulação da Expressão Gênica/efeitos dos fármacos , Doenças das Valvas Cardíacas/genética , Doenças das Valvas Cardíacas/metabolismo , Doenças das Valvas Cardíacas/patologia , Doenças das Valvas Cardíacas/prevenção & controle , Humanos , Simulação de Acoplamento Molecular , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Fator de Necrose Tumoral alfa/efeitos adversos
5.
Nat Rev Cardiol ; 16(5): 305-318, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30675027

RESUMO

Epidemiological and clinical studies over the past decade have firmly established that elevated plasma concentrations of lipoprotein(a) (Lp(a)) are an important, independent and probably causal risk factor for the development of cardiovascular diseases. Whereas a link between Lp(a) levels and atherosclerotic cardiovascular disease (ASCVD) has been appreciated for decades, the role of Lp(a) in calcific aortic valve disease (CAVD) and aortic stenosis has come into focus only in the past 5 years. ASCVD and CAVD are aetiologically distinct but have several risk factors in common and similar pathological processes at the cellular and molecular levels. Oxidized phospholipids, which modify Lp(a) primarily by covalent binding to its unique apolipoprotein(a) (apo(a)) component, might hold the key to Lp(a) pathogenicity and provide a mechanistic link between ASCVD and CAVD. Oxidized phospholipids colocalize with apo(a)-Lp(a) in arterial and aortic valve lesions and directly participate in the pathogenesis of these disorders by promoting endothelial dysfunction, lipid deposition, inflammation and osteogenic differentiation, leading to calcification. The advent of potent Lp(a)-lowering therapies provides the opportunity to address directly the causality of Lp(a) in ASCVD and CAVD and, more importantly, to provide both a novel approach to reduce the residual risk of ASCVD and a long-sought medical treatment for CAVD.


Assuntos
Estenose da Valva Aórtica , Valva Aórtica/patologia , Calcinose , Doença da Artéria Coronariana , Lipoproteína(a)/metabolismo , Fosfolipídeos/metabolismo , Calcificação Vascular/metabolismo , Valva Aórtica/metabolismo , Estenose da Valva Aórtica/metabolismo , Estenose da Valva Aórtica/prevenção & controle , Calcinose/metabolismo , Calcinose/prevenção & controle , Doença da Artéria Coronariana/metabolismo , Doença da Artéria Coronariana/prevenção & controle , Descoberta de Drogas , Humanos , Oxirredução
6.
PLoS One ; 13(12): e0208774, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30532256

RESUMO

The development of a substance or inhibitor-based treatment strategy for the prevention of aortic valve stenosis is a challenge and a main focus of medical research in this area. One strategy may be to use the tankyrase inhibitor XAV-939, which leads to Axin stabilisation and subsequent destruction of the ß-catenin complex and dephosphorylation of ß-catenin. The dephosphorylated active form of ß-catenin (non-phospho-ß-catenin) then promotes nuclear transcription that leads to osteogenesis. The aims of the present study were to develop an experimental system for inducing in vitro calcification of human aortic valvular interstitial cells (VICs) to investigate the potential anti-calcific effect of XAV-939 and to analyse expression of the Wnt signalling proteins and Sox9, a chondrogenesis regulator, in this model. Calcification of human VIC cultures was induced by cultivation in an osteogenic medium and the effect of co-incubation with 1µM XAV-939 was monitored. Calcification was quantified when mineral deposits were visible in culture and was histologically verified by von Kossa or Alizarin red staining and by IR-spectroscopy. Protein expression of alkaline phosphatase, Axin, ß-catenin and Sox9 were quantified by western blotting. In 58% of the VIC preparations, calcification was induced in an osteogenic culture medium and was accompanied by upregulation of alkaline phosphatase. The calcification induction was prevented by the XAV-939 co-treatment and the alkaline phosphatase upregulation was suppressed. As expected, Axin was upregulated, but the levels of active non-phospho-ß-catenin were also enhanced. Sox9 was induced during XAV-939 treatment but apparently not as a result of downregulation of ß-catenin signalling. XAV-939 was therefore able to prevent calcification of human VIC cultures, and XAV-939 treatment was accompanied by upregulation of active non-phospho-ß-catenin. Although XAV-939 does not downregulate active ß-catenin, treatment with XAV-939 results in Sox9 upregulation that may prevent the calcification process.


Assuntos
Estenose da Valva Aórtica/prevenção & controle , Valva Aórtica/efeitos dos fármacos , Calcinose/prevenção & controle , Fármacos Cardiovasculares/farmacologia , Compostos Heterocíclicos com 3 Anéis/farmacologia , Substâncias Protetoras/farmacologia , Idoso , Fosfatase Alcalina/metabolismo , Valva Aórtica/metabolismo , Valva Aórtica/patologia , Estenose da Valva Aórtica/metabolismo , Estenose da Valva Aórtica/patologia , Calcinose/metabolismo , Calcinose/patologia , Células Cultivadas , Feminino , Humanos , Masculino , Fatores de Transcrição SOX9/metabolismo , Proteínas Wnt/metabolismo , beta Catenina/metabolismo
7.
J Mater Sci Mater Med ; 29(11): 175, 2018 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-30413947

RESUMO

Heart valve diseases remain common in industrialized countries. Bioprosthetic heart valves, introduced as free of anticoagulation therapy alternatives to mechanical substitutes. Still they suffer from long term failure due to calcification. Different treatment methods introduced to inhibit calcification, have so far been limited in success. Glycosaminoglycans (GAGs) possess properties including high negative charge, anticoagulation and anti-inflammatory activity that make them a potential solution for calcification problem. In this study, heparin hydrogel was prepared and characterized both chemically and mechanically. After that, heparin hydrogel embedded bovine pericardial tissues, fixed with glutaraldehyde, were produced and tested for their mechanical behavior and anticalcifcation potential in vitro using the constant composition model. In the calcification experiments, tissues were divided into three groups: a) Controls without treatment, b) Hydrogel treated tissues and c) Tissues with raw heparin dissolved in the calcification solution. The results showed that embedding of tissue with hydrogel had no stiffening effect on its mechanical behavior. Calcification assessment showed a significant efficacy on inhibition of calcium phosphate deposition of hydrogel treated (second group) in comparison to untreated tissues (control, first group). Calcification inhibition potential was very similar in both the second and raw heparin (third group). Histological data confirmed the obtained results, suggesting that heparin treatment is a promising anticalcification agent.


Assuntos
Glutaral/química , Próteses Valvulares Cardíacas , Heparina/química , Hidrogéis/química , Pericárdio/química , Animais , Fenômenos Biomecânicos , Bioprótese , Calcificação Fisiológica/efeitos dos fármacos , Calcinose/prevenção & controle , Cálcio , Bovinos , Fixação de Tecidos
8.
J Am Heart Assoc ; 7(20): e007861, 2018 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-30371255

RESUMO

Background Aortic valve sclerosis ( AVS c), the early asymptomatic presentation of calcific aortic valve (AV) disease, affects 25% to 30% of patients aged >65 years. In vitro and ex vivo experiments with antioxidant strategies and antagonists of osteogenic differentiation revealed that AVS c is reversible. In this study, we characterized the underlying changes in the extracellular matrix architecture and valve interstitial cell activation in AVSc and tested in vitro and in vivo the activity of a clinically approved SOD (superoxide dismutase) mimic and redox-active drug MnTnBu OE -2-PyP5+ ( BMX -001). Methods and Results After receiving informed consent, samples from patients with AVS c, AV stenosis, and controls were collected. Uniaxial mechanical stimulation and in vitro studies on human valve interstitial cells were performed. An angiotensin II chronic infusion model was used to impose AV thickening and remodeling. We characterized extracellular matrix structures by small-angle light scattering, scanning electron microscopy, histology, and mass spectrometry. Diseased human valves showed altered collagen fiber alignment and ultrastructural changes in AVS c, accumulation of oxidized cross-linking products in AV stenosis, and reversible expression of extracellular matrix regulators ex vivo. We demonstrated that MnTnBu OE -2-PyP5+ inhibits human valve interstitial cell activation and extracellular matrix remodeling in a murine model (C57 BL /6J) of AVS c by electron microscopy and histology. Conclusions AVS c is associated with architectural remodeling despite marginal effects on the mechanical properties in both human and mice. MnTnBu OE -2-PyP5+ controls AV thickening in a murine model of AVS c. Because this compound has been approved recently for clinical use, this work could shift the focus for the treatment of calcific AV disease, moving from AV stenosis to an earlier presentation ( AVS c) that could be more responsive to medical therapies.


Assuntos
Valva Aórtica/patologia , Fármacos Cardiovasculares/farmacologia , Metaloporfirinas/farmacologia , Idoso , Animais , Valva Aórtica/efeitos dos fármacos , Estenose da Valva Aórtica/prevenção & controle , Calcinose/prevenção & controle , Estudos de Casos e Controles , Colágeno/efeitos dos fármacos , Modelos Animais de Doenças , Matriz Extracelular/efeitos dos fármacos , Feminino , Humanos , Masculino , Camundongos Endogâmicos C57BL , Microscopia Eletrônica de Varredura , Pessoa de Meia-Idade , Esclerose/prevenção & controle , Superóxido Dismutase/antagonistas & inibidores , Remodelação Vascular/efeitos dos fármacos
9.
Acta Biomater ; 82: 44-55, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30326277

RESUMO

In recent years, the number of heart valve replacements has multiplied with valve diseases because of aging populations and the surge in rheumatic heart disease in young people. Among them, bioprosthetic heart valves (BHVs) have become increasingly popular. Transcatheter aortic valve implantation (TAVI) valve as an emerging BHV has been increasingly applied to patients. However, the current commercially used BHVs treated with glutaraldehyde (Glut) still face the problem of durability. BHVs derived from Glut-treated xenogenetic tissues would undergo structural degeneration and calcification sometimes even as short as less than 10 years. This issue has already become a big challenge considering more and more young patients at the age of 50-60 s are receiving the BHV replacement. In our study, an approach that is totally different from the previous techniques named by us as the radical polymerization-crosslinking (RPC) method was developed to improve extracellular matrix stability, prevent calcification, and reduce inflammatory response in BHVs. The porcine pericardium (PP) tissue was decellularized, functionalized with methacryloyl groups, and subsequently crosslinked by radical polymerization. We found that high-density RPC treatment remarkably improved the stability of collagen and elastin of PP, enhanced its endothelialization potential, and provided reliable biomechanical performance as compared to Glut treatment. The in vivo rat model also confirmed the increased componential stability and the reduced inflammatory response of RPC-treated PP. Moreover, the RPC-treated PP showed better in vivo anticalcification potential than Glut-treated PP. STATEMENT OF SIGNIFICANCE: Bioprosthetic heart valves (BHVs) manufactured from glutaraldehyde (Glut)-treated xenogeneic tissues have been used to treat valve-related diseases for several decades. However, the durability of BHVs remains unresolved and becomes more pronounced particularly in younger patients. Although a number of new alternative methods for Glut crosslinking have been proposed, their overall performance is still far from ready to use in humans. In this study, radical polymerization was investigated for crosslinking the porcine pericardium (PP). This treatment was found to have advantages compared to Glut-treated PP in terms of stability, biocompatibility, and anticalcification potential with the hope of addressing the needs of more robust biomaterials for the fabrication of BHVs.


Assuntos
Bioprótese , Calcinose/prevenção & controle , Matriz Extracelular/química , Próteses Valvulares Cardíacas , Pericárdio/química , Animais , Linhagem Celular , Humanos , Teste de Materiais , Camundongos , Suínos
10.
Pharmacol Res ; 136: 74-82, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30149054

RESUMO

Calcific aortic valve disease (CAVD) is the most common valvular disorder in the elderly, with the incidence of 3% in general population of Western countries. The initial phase of CAVD is characterized by leaflet thickening and possible spotty calcification (i.e. aortic valve sclerosis (AVSc)), while advanced stages have leaflets structure degeneration (i.e. aortic valve stenosis (AS)). The pathological cellular and molecular mechanisms, involved in CAVD, are extracellular matrix degradation, aberrant matrix deposition, fibrosis, mineralization, inflammation, lipid accumulation, and neo-angiogenesis. CAVD clinical risk shares considerable overlap with those of atherosclerosis and they include hypertension, smoking habits, and hyperlipidemia. Unfortunately, surgical aortic valve replacement and transcatheter aortic valve implantation are the only available treatments when the disease become severe and symptoms occur. Indeed, no approved pharmacological approach is available for CAVD patients. In this review, we describe the current literature evidence on possible future therapeutic targets for this debilitating and fatal disease such as PCSK9, P2Y2 receptor, cadherin 11, and DDP-4.


Assuntos
Valva Aórtica/patologia , Calcinose/tratamento farmacológico , Doenças das Valvas Cardíacas/tratamento farmacológico , Animais , Calcinose/metabolismo , Calcinose/prevenção & controle , Genômica , Doenças das Valvas Cardíacas/metabolismo , Doenças das Valvas Cardíacas/prevenção & controle , Humanos , Hipolipemiantes/uso terapêutico
11.
Artif Organs ; 42(11): 1062-1069, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30058211

RESUMO

The lifetime of bioprosthetic heart valves (BHVs) is limited by the mechanical damage and calcification. The major components of BHVs are collagen and elastin. Collagen could be well protected by glutaraldehyde (GLUT) crosslinking, while elastin is not stabilized and has a high risk of degradation, which could lead to the calcification of BHVs. We aimed to develop methods for stabilizing elastin and decreasing calcification. We investigated the combined tannic acid (TA) or epigallocatechin gallate (EGCG) with ferric chloride to stabilize elastin and prevent calcification. We found that the amount of TA/EGCG bound to elastin was in a time-dependent pattern and this reaction showed better efficiency in acidic condition and ethanol-water mixed solvents. Moreover, Fe3+ could compete with Ca2+ to bind to polyphenol, which could reduce the calcium deposition on BHVs. Cytotoxicity test showed that all extracts from different treatments had similar cell viabilities (85-100%). Through the combined treatments of polyphenol and ferric chloride, the pericardium had a better resistance to elastase degradation and more excellent anticalcification performance.


Assuntos
Bioprótese , Calcinose/prevenção & controle , Cloretos/química , Elastina/química , Compostos Férricos/química , Próteses Valvulares Cardíacas , Pericárdio/química , Polifenóis/química , Animais , Catequina/análogos & derivados , Catequina/química , Colágeno/química , Reagentes para Ligações Cruzadas/química , Glutaral/química , Masculino , Pericárdio/ultraestrutura , Estabilidade Proteica , Ratos Sprague-Dawley , Suínos , Taninos/química , Resistência à Tração
12.
Int J Cardiol ; 269: 226-228, 2018 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-30054144

RESUMO

BACKGROUND: Calcific aortic valve stenosis (CAVS) is the most prevalent heart valve disease in Western societies. The American Heart Association 2020 Strategic Impact Goals introduced the concept of ideal cardiovascular health, which includes seven cardiovascular health metrics, namely body mass index, a healthy diet, physical activity, smoking status, blood pressure, fasting plasma glucose and cholesterol levels. Several prospective studies have shown that compared to people who meet few of the criteria of ideal cardiovascular health, those with ideal cardiovascular health have an 80-90% lower risk of cardiovascular events. Whether or not ideal cardiovascular health is associated with CAVS risk is unknown. The purpose of this study was to assess the association between ideal cardiovascular health status and the risk of CAVS. METHODS: In this analysis of the EPIC-Norfolk study, 21,856 participants were followed for 11.5 years and 430 of them developed CAVS. A cardiovascular health score was calculated based on the number of the seven health metrics. RESULTS: In comparison to individuals in the bottom quartile of ideal cardiovascular health (CAVS event rate of 2,9%), those in the top quartile of the ideal cardiovascular health score had a relative risk of CAVS of 0,45 (95% CI 0,31-0,65, AVS event rate of 0,8%). CONCLUSIONS: In apparently healthy individuals, modifiable clinical and lifestyle-related risk factors for CVD are strongly associated with the risk of CAVS, thereby suggesting that CAVS may be a preventable disease.


Assuntos
Estenose da Valva Aórtica/epidemiologia , Estenose da Valva Aórtica/prevenção & controle , Valva Aórtica/patologia , Calcinose/epidemiologia , Calcinose/prevenção & controle , Nível de Saúde , Estilo de Vida , Valva Aórtica/fisiopatologia , Estenose da Valva Aórtica/fisiopatologia , Pressão Sanguínea/fisiologia , Índice de Massa Corporal , Calcinose/fisiopatologia , Estudos de Coortes , Feminino , Seguimentos , Humanos , Incidência , Masculino , Fatores de Risco
13.
Plast Reconstr Surg ; 142(3): 699-707, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29927835

RESUMO

BACKGROUND: Calcium gluconate extravasation is a process that can cause serious lesions, such as necrosis and calcification of the soft tissues. The aim of the present study was to analyze the beneficial effects of four possible local antidotes for calcium gluconate extravasation: hyaluronidase, sodium thiosulfate, triamcinolone acetonide, and physiologic saline solution. METHODS: Seventy-four BALB/c mice were used in the study. The substances selected for use in this study were calcium gluconate (4.6 mEq/ml), hyaluronidase (1500 IU/ml), sodium thiosulfate (25%), triamcinolone acetonide (40 mg/ml 0.5 mg/kg), and saline solution 0.9%. Five minutes were allowed to lapse after the calcium gluconate infiltration, and then an antidote was infiltrated. After 3 weeks, a skin biopsy was performed and a radiographic and histologic study was carried out. RESULTS: Only in the group infiltrated with sodium thiosulfate did all skin lesions disappear after the 3-week period after infiltration. In the radiographic study, calcium deposits larger than 0.5 mm were observed in 40 percent of cases without an antidote, in 33 percent with triamcinolone acetonide, in 13 percent with a saline solution, and in none with thiosulfate and hyaluronidase. In the histologic study, calcium deposits were found in 53 percent of cases without antidote, 100 percent of cases with triamcinolone acetonide, 33 percent of cases with saline solution, and 13 percent of cases with sodium thiosulfate or hyaluronidase. CONCLUSION: Sodium thiosulfate and hyaluronidase prevent the development of calcium deposits after calcium gluconate extravasation.


Assuntos
Antídotos/uso terapêutico , Calcinose/induzido quimicamente , Calcinose/prevenção & controle , Gluconato de Cálcio/efeitos adversos , Dermatopatias/induzido quimicamente , Dermatopatias/prevenção & controle , Animais , Hialuronoglucosaminidase/uso terapêutico , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Estudos Prospectivos , Solução Salina/uso terapêutico , Tiossulfatos/uso terapêutico , Resultado do Tratamento , Triancinolona Acetonida/uso terapêutico
14.
J Cardiothorac Surg ; 13(1): 34, 2018 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-29695259

RESUMO

BACKGROUND: Glutaraldehyde fixed xenogeneic heart valve prosthesis are hindered by calcification and lack of growth potential. The aim of tissue decellularization is to remove tissue antigenicity, avoiding the use of glutaraldehyde and improve valve integration with low inflammation and host cell recolonization. In this preliminary study, we investigated the efficacy of a NaOH-based process for decellularization and biocompatibility improvement of porcine pulmonary heart valves in comparison to a detergent-based process (SDS-SDC0, 5%). METHODS: Native cryopreserved porcine pulmonary heart valves were treated with detergent and NaOH-based processes. Decellularization was assessed by Hematoxylin and eosin/DAPI/alpha-gal/SLA-I staining and DNA quantification of native and processed leaflets, walls and muscles. Elongation stress test investigated mechanical integrity of leaflets and walls (n = 3 tests/valve component) of valves in the native and treated groups (n = 4/group). Biochemical integrity (collagen/elastin/glycosaminoglycans content) of leaflet-wall and muscle of the valves (n = 4/group) was assessed and compared between groups with trichrome staining (Sirius Red/Miller/Alcian blue). Secondly, a preliminary in vivo study assessed biocompatibility (CD3 and CD68 immunostaining) and remodeling (Hematoxylin and eosin/CD31 and ASMA immunofluorescent staining) of NaOH processed valves implanted in orthotopic position in young Landrace pigs, at 1 (n = 1) and 3 months (n = 2). RESULTS: Decellularization was better achieved with the NaOH-based process (92% vs 69% DNA reduction in the wall). Both treatments did not significantly alter mechanical properties. The detergent-based process induced a significant loss of glycosaminoglycans (p < 0,05). In vivo, explanted valves exhibited normal morphology without any sign of graft dilatation, degeneration or rejection. Low inflammation was noticed at one and three months follow-up (1,8 +/- 3,03 and 0,9836 +/- 1,3605 CD3 cells/0,12 mm2 in the leaflets). In one animal, at three months we documented minimal calcification in the area of sinus leaflet and in one, microthrombi formation on the leaflet surface at 1 month. The endoluminal side of the valves showed partial reendothelialization. CONCLUSIONS: NaOH-based process offers better porcine pulmonary valve decellularization than the detergent process. In vivo, the NaOH processed valves showed low inflammatory response at 3 months and partial recellularization. Regarding additional property of securing, this treatment should be considered for the new generation of heart valves prosthesis. Graphical abstract of the study.


Assuntos
Bioprótese , Criopreservação/métodos , Detergentes , Próteses Valvulares Cardíacas , Valva Pulmonar , Hidróxido de Sódio , Animais , Fenômenos Biomecânicos , Calcinose/prevenção & controle , Colágeno/análise , Elastina/análise , Glicosaminoglicanos/análise , Implante de Prótese de Valva Cardíaca , Xenoenxertos , Valva Pulmonar/química , Valva Pulmonar/transplante , Suínos , Engenharia Tecidual/métodos
15.
Sci Rep ; 8(1): 5812, 2018 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-29643466

RESUMO

Cardiovascular calcification is associated with high risk of vascular disease. This involves macrophage infiltration of injured vascular tissue and osteoclast-related processes. Splenic monocytes from mice, that are predisposed (C3H) or resistant (B6) to calcification, were isolated and differentiated in vitro with M-CSF to generate macrophages, which aggregate to form multinucleated (MN) cells in the presence of RANKL. MN cell formation was significantly decreased in monocytes from resistant compared with calcifying mice. Conditioned media from C3H macrophages strongly induced calcification in vitro. However, medium from B6 macrophages inhibited calcification. An increase in ICAM-1 was detected in conditioned media from C3H macrophages compared with B6, suggesting a key role for this molecule in calcification processes. Due to natural genetic loss of Abcc6, the causal gene for cardiac calcification, C3H mice have reduced plasma levels of inorganic pyrophosphate (PPi), a potential calcification inhibitor. Supplementation of C3H mice with PPi or Etidronate prevented but did not completely reverse cardiac calcification. Our data provide strong evidence of the pathogenesis of macrophages and MNs during tissue calcification and suggest PPi or its analogue Etidronate as a potential inhibitor of MN formation and calcification. Furthermore, the adhesion molecule ICAM-1 was shown to play a key role in calcification.


Assuntos
Conservadores da Densidade Óssea/administração & dosagem , Calcinose/prevenção & controle , Doenças Cardiovasculares/prevenção & controle , Agregação Celular/efeitos dos fármacos , Ácido Etidrônico/administração & dosagem , Macrófagos/efeitos dos fármacos , Animais , Células Cultivadas , Difosfatos/administração & dosagem , Molécula 1 de Adesão Intercelular/análise , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL
16.
Acta otorrinolaringol. esp ; 69(2): 61-66, mar.-abr. 2018. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-172134

RESUMO

Introducción y objetivos: Los tonsilolitos y alteraciones en el complejo estilohioideo pueden presentar similar sintomatología a otras de diferente etiología. Los individuos con fisura labiopalatina describen similares síntomas en razón de las repercusiones anatómicas propias de esta anomalía. El objetivo de este estudio fue determinar la prevalencia de alteraciones del complejo estilohioideo y tonsilolitos en exámenes de tomografía computarizada de haz cónico en individuos con fisura labiopalatina. Métodos: Según criterios de inclusión y exclusión fueron analizadas 66 tomografías de 2.794 tomografías, en el software i- Cat visión ® con índice Kappa 0,8 intraexaminador. Resultados: La prevalencia total de osificación del complejo estilohioideo incompleto en individuos con fisura labiopalatina fue de 66,6%, la prevalencia de estos hallazgos en el género femenino fue de 75% y 61,9% en el género masculino. La prevalencia total de tonsilolitos fue de 7,5%. Conclusión: Es de relevancia constatar en el informe radiológico la presencia de la calcificación del complejo estilo-hioideo y tonsilolitos. Debido a la proximidad anatómica y similar sintomatología clínica con otras alteraciones orofaciales presentes en los individuos con fisura labiopalatina, haciendo énfasis en individuos con fisura labiopalatina del género femenino, pacientes con fisura tipo transformen incisivo y posforamen incisivo por presentar mayor prevalencia. Conocer más sobre la morfometría anatómica de individuos con fisura labiopalatina coadyuva relevantemente en la elección de conductas clínicas y calidad de vida de estos pacientes, teniendo presente que la fisura labiopalatina es una de las anomalías más comunes (AU)


Introduction and objectives: Tonsilloliths and abnormal stylohyoid complex may have similar symptoms to others of different aetiology. Individuals with cleft lip and palate describe similar symptoms because of the anatomical implications that are peculiar to this anomaly. The aim of this study was to determine the prevalence of abnormal stylohyoid complex and tonsilloliths on cone beam computed tomography in individuals with cleft lip and palate. Methods: According to the inclusion and exclusion criteria, 66 CT scans out of of 2,794 were analysed, on i- Cat ® vision software with 0.8 index Kappa intra-examiner. Results: The total prevalence of ossification of the incomplete stylohyoid complex in individuals with cleft lip and palate was 66.6%; the prevalence of these findings in females was 75% and 61.9% in males. The total prevalence of tonsilloliths was 7.5%. Conclusion: It is important to ascertain calcification of the stylohyoid complex and tonsilloliths in the radiological report, due to the anatomical proximity and similarsymptomatology to other orofacial impairments inindividuals with cleft lip and palate, focusing on females with oral cleft formation, patients with incisive trans foramen cleft and incisive post foramen cleft because they are more prevalent. Greater knowledge of the anatomical morphometry of individuals with cleft lip and palate greatly contributes towards the selection of clinical behaviours and the quality of life of these patients, since cleft lip and palateis one of the most common anomalies (AU)


Assuntos
Humanos , Masculino , Feminino , Adulto Jovem , Calcinose/diagnóstico por imagem , Calcinose/etiologia , Calcinose/terapia , Tomografia Computadorizada por Raios X/métodos , Tonsila Palatina/diagnóstico por imagem , Calcinose/prevenção & controle , Tomografia Computadorizada por Raios X/tendências , Tonsila Palatina/lesões , Tonsila Faríngea/diagnóstico por imagem
17.
J Thorac Cardiovasc Surg ; 156(1): 197-206, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29572021

RESUMO

OBJECTIVE: With the increasing use of bioprostheses worldwide, continuous efforts have been made to improve tissue durability. We introduce a new treatment for bovine pericardium combining octanediol-ethanol based phospholipid removal with taurine-based glutaraldehyde neutralization and storage in an aldehyde-free solution (FREE). METHODS: Treated tissues were evaluated by mechanical and biochemical characterization, phospholipid content, aldehyde levels, cell cultures on pericardial samples (L929 fibroblasts and human umbilical vein endothelial cells), rat subcutaneous implantations, and long-term juvenile sheep mitral valve implantations (n = 3). Comparisons were made to glutaraldehyde-fixed bovine pericardium or to samples from commercially available biological valves (ie, Trifecta [St Jude Medical, Saint Paul, Minn] and Perimount Magna Ease [Edwards Lifesciences, Irvine, Calif]). RESULTS: FREE-treated pericardium had similar mechanical strength and biochemical properties as commercially available valves. Compared with glutaraldehyde-only samples, FREE-treated samples showed lower phospholipid levels (P < .01), significantly better growth of L929 fibroblasts, and lower calcification levels in rat subcutaneous implants (P < .01). Compared with samples from Linx- (Trifecta) and ThermaFix-treated (Perimount Magna Ease) valves, similar low levels of phospholipids were observed as were similar low calcification levels in subcutaneous implants, but tissue extractions from FREE-treated samples showed the lowest levels of extracted aldehydes (P < .01). Mitral implants of FREE-treated valves in juvenile sheep had excellent hemodynamic behavior without any sign of degeneration or calcification at 5 months. CONCLUSIONS: The new FREE treatment combines an adequate phospholipid reduction and aldehyde neutralization with storage in an aldehyde-free solution. This combination enhances the anticalcification properties and may thereby improve long-term durability of the tissue.


Assuntos
Bioprótese , Calcinose/prevenção & controle , Implante de Prótese de Valva Cardíaca/instrumentação , Próteses Valvulares Cardíacas , Pericárdio/transplante , Fixação de Tecidos/métodos , Aldeídos/metabolismo , Animais , Calcinose/etiologia , Calcinose/metabolismo , Calcinose/patologia , Bovinos , Linhagem Celular , Etanol/química , Fibroblastos/metabolismo , Fibroblastos/patologia , Fixadores/química , Glutaral/química , Implante de Prótese de Valva Cardíaca/efeitos adversos , Xenoenxertos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Células Endoteliais da Veia Umbilical Humana/patologia , Humanos , Hidroxiprolina/metabolismo , Teste de Materiais , Octanóis/química , Pericárdio/metabolismo , Pericárdio/patologia , Fosfolipídeos/metabolismo , Desenho de Prótese , Ratos Wistar , Carneiro Doméstico , Resistência à Tração , Fatores de Tempo
18.
J Am Heart Assoc ; 7(3)2018 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-29431107

RESUMO

BACKGROUND: The relationship between ideal cardiovascular health reflected in the cardiovascular health score (CVHS) and valvular heart disease is not known. The purpose of this study was to determine the association of CVHS attainment through midlife to late life with aortic stenosis prevalence and severity in late life. METHODS AND RESULTS: The following 6 ideal cardiovascular health metrics were assessed in ARIC (Atherosclerosis Risk in Communities) Study participants at 5 examination visits between 1987 and 2013 (visits 1-4 in 1987-1998 and visit 5 in 2011-2013): smoking, body mass index, total cholesterol, blood pressure, physical activity, and blood glucose. Percentage attained CVHS was calculated in 6034 participants as the sum of CVHS at each visit/the maximum possible score. Aortic stenosis was assessed by echocardiography at visit 5 on the basis of the peak aortic valve velocity. Aortic stenosis was categorized sclerosis, mild stenosis, and moderate-to-severe stenosis. Mean age was 76±5 years, 42% were men, and 22% were black. Mean percentage attained CVHS was 63±14%, and the prevalence of aortic stenosis stages were 15.9% for sclerosis, 4.3% for mild stenosis, and 0.7% for moderate-to-severe stenosis. Worse percentage attained CVHS was associated with higher prevalence of aortic sclerosis (P<0.001 for trend), mild stenosis (P<0.001), and moderate-to-severe stenosis (P=0.002), adjusting for age, sex, and race. CONCLUSIONS: Greater attainment of ideal cardiovascular health in midlife to late life is associated with a lower prevalence of aortic sclerosis and stenosis in late life in a large cohort of older adults.


Assuntos
Estenose da Valva Aórtica/epidemiologia , Valva Aórtica/patologia , Calcinose/epidemiologia , Nível de Saúde , Estilo de Vida , Idoso , Idoso de 80 Anos ou mais , Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/prevenção & controle , Biomarcadores/sangue , Glicemia/análise , Pressão Sanguínea , Índice de Massa Corporal , Calcinose/diagnóstico por imagem , Calcinose/prevenção & controle , Colesterol/sangue , Ecocardiografia Doppler , Exercício , Feminino , Avaliação Geriátrica/métodos , Humanos , Masculino , Prevalência , Fatores de Proteção , Medição de Risco , Fatores de Risco , Comportamento de Redução do Risco , Índice de Gravidade de Doença , Fumar/efeitos adversos , Fumar/epidemiologia , Abandono do Hábito de Fumar , Estados Unidos/epidemiologia
19.
Eur J Prev Cardiol ; 25(5): 551-556, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29376752

RESUMO

Background Aortic stenosis is the most common cause of valvular heart disease with no means of prevention. Lowering serum levels of calcium or phosphate are potential preventive strategies but observational studies on the associations with aortic stenosis are inconsistent. Design and methods A case-control study was conducted in 132 individuals undergoing echocardiography (63 with aortic stenosis and 69 without) and the results combined with three other comparable studies (914 individuals overall) to provide a summary odds ratio of aortic stenosis for a 0.1 mmol/L increase (approximately one standard deviation) in calcium and phosphate respectively. The relationship between calcium and phosphate and the severity of aortic stenosis, according to peak trans-aortic velocity, was also examined in the case-control study using linear regression. Results Both calcium and phosphate were positively associated with aortic stenosis. The summary odds ratio for a 0.1 mmol/L increase in calcium was 1.79 (95% confidence interval 1.07-2.99), p = 0.027 and for phosphate it was 1.47 (1.08-2.01), p = 0.015. Peak trans-aortic velocity increased with phosphate levels, 9% (4%-14%) per 0.1 mmol/L, p = 0.001, but not with calcium, p = 0.089. Conclusions If the associations are causal and reversible, these results indicate that a small reduction in calcium or phosphate levels, within the physiological rage, would translate into a clinically significant reduction in the risk of aortic stenosis. Randomised trials of calcium and phosphate lowering therapies in aortic stenosis are needed.


Assuntos
Estenose da Valva Aórtica/prevenção & controle , Valva Aórtica/diagnóstico por imagem , Calcinose/prevenção & controle , Cálcio/sangue , Fosfatos/sangue , Idoso , Idoso de 80 Anos ou mais , Estenose da Valva Aórtica/sangue , Estenose da Valva Aórtica/etiologia , Biomarcadores/sangue , Calcinose/sangue , Calcinose/complicações , Ecocardiografia , Feminino , Seguimentos , Humanos , Masculino , Estudos Retrospectivos
20.
Cardiovasc Pathol ; 32: 1-7, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29049912

RESUMO

Vascular xenografts are widely used in cardiovascular surgery as an alternative to autologous vessels and vascular allografts. Calcification is one of the main drawbacks of vascular grafts, especially among young patients and children. Among different anticalcification approaches, chitosan emerges as a highly promising candidate due to its versatility, natural origin, and biocompatibility. We investigated the anticalcification efficacy of globular chitosan ("Chitozol") as it demonstrated the improved rate of water solubility as compared with conventional linear macromolecules of chitosan. In addition, we supposed that compact globular form of "Chitozol" molecules could provide effective penetration of extracellular matrix of bovine jugular veins (BJVs). Our results revealed that "Chitozol" treatment mitigated calcification in the experimental groups as compared to the control groups (without any treatment, conventional treatment with glutaraldehyde, and commercially available Contegra conduit). Different concentrations of "Chitozol" (0.3% and 3%), as well as different incubation times (15 and 30min), were equally effective in the prevention of calcification. In addition, "Chitozol" treatment with decellularization of BJVs demonstrated slightly improved stress-strain properties of unimplanted samples. Thus, the filling of fresh BJV with globular chitosan is proposed as a promising emerging treatment for the mitigation of calcific degeneration in BJVs xenografts.


Assuntos
Calcinose/prevenção & controle , Quitosana/farmacologia , Xenoenxertos/patologia , Veias Jugulares/transplante , Animais , Bovinos , Modelos Animais de Doenças , Xenoenxertos/efeitos dos fármacos , Ratos
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