Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.843
Filtrar
1.
Asian Cardiovasc Thorac Ann ; 28(7): 381-383, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33023307
2.
Eur J Endocrinol ; 183(4): 463-470, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32822316

RESUMO

Objective: Turner syndrome (TS) is a rare disorder affecting 1/2500 female newborn. Aortic dilatation (AD) and aortic dissection represent a major concern in TS. The aims of our study were to describe the aortic root growth, potential aortic dilatation (AD) risk factors and cardiovascular outcomes in a cohort of patients with TS. Methods: Among 204 adult patients included, 197 were studied using a standardized 1.5 Tesla MRI protocol. AD was defined as an aortic diameter ≥20 mm/m2 at the Valsalva sinuses and/or at the ascending aorta, when indexed to body surface area. Results: At baseline, AD was present in 81/197 (41.1%) and 32/197 (16.2%) of patients, at the levels of Valsalva and ascending aorta, respectively. The aortic Valsalva diameter was larger in patients treated for thyroiditis (P < 0.001). Potential risk factors of AD were aging (P < 0.001) and the presence of bicuspid aortic valve (BAV) (P = 0.002). The hazard ratio (HR) of AD occurrence in the presence of BAV was 2.2 (95% CI: 1.33-3.71). After a median follow-up period of 5.1 years (n = 143), AD was present in 58/143 (40.6%) and 25/143 (17.5%) of patients at the levels of Valsalva and ascending aorta, respectively. The median aortic growth of the Valsalva sinuses remained stable. At the ascending aorta, it increased by 0.14 ± 0.61 mm/year. Only one aortic-related death was observed. Conclusion: AD is common in adult patients with TS. However, our results are rather reassuring, as the median aortic diameters remained stable after 5.1 years and few aortic events were observed.


Assuntos
Doenças da Aorta/epidemiologia , Síndrome de Turner/epidemiologia , Adulto , Aorta/diagnóstico por imagem , Aorta/patologia , Doenças da Aorta/complicações , Doenças da Aorta/diagnóstico , Valva Aórtica/anormalidades , Valva Aórtica/patologia , Estudos de Coortes , Dilatação Patológica/complicações , Dilatação Patológica/diagnóstico , Dilatação Patológica/epidemiologia , Progressão da Doença , Feminino , França/epidemiologia , Doenças das Valvas Cardíacas/complicações , Doenças das Valvas Cardíacas/diagnóstico , Doenças das Valvas Cardíacas/epidemiologia , Doenças das Valvas Cardíacas/patologia , Humanos , Masculino , Prevalência , Síndrome de Turner/complicações , Adulto Jovem
3.
Prog Cardiovasc Dis ; 63(4): 475-481, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32640281

RESUMO

Patients with a bicuspid aortic valve (BAV) frequently develop aneurysms of the aortic root and tubular ascending aorta. Aneurysms of the aortic arch, in the absence of concomitant aortopathies, are much less common. According to the 2018 American Association of Thoracic Surgery consensus guidelines on BAV-related aortopathy, prophylactic surgical aortic repair / replacement is recommended starting at a maximum aortic diameter of 50 mm in patients with risk factors. Concomitant aortic surgery is also recommended at an aortic diameter of 45 mm in those patients with other indications for cardiac surgery (most commonly aortic valve procedures). The ultimate goal of prophylactic aortic surgery is the prevention of aortic catastrophes, e.g. aortic rupture or acute aortic dissection, which are associated with high morbidity and mortality. The surgical technique used - in elective and emergency cases - depends on the involvement and nature of the aortic valve disease, as well as the extent of aortic aneurysm formation. The current review focusses on the surgical management of the aortic root, tubular ascending aorta, and proximal aortic arch in BAV patients. Despite the abovementioned recommendations, many BAV patients develop acute aortic syndromes below the recommended aortic diameter thresholds. Further research is therefore required in order to identify high-risk BAV subgroups that would benefit from earlier surgical repair.


Assuntos
Aneurisma Aórtico/cirurgia , Valva Aórtica/anormalidades , Doenças das Valvas Cardíacas/complicações , Doenças das Valvas Cardíacas/cirurgia , Aneurisma Aórtico/diagnóstico , Aneurisma Aórtico/etiologia , Valva Aórtica/patologia , Valva Aórtica/cirurgia , Implante de Prótese Vascular , Anuloplastia da Valva Cardíaca , Doenças das Valvas Cardíacas/patologia , Humanos , Técnicas de Sutura
4.
Prog Cardiovasc Dis ; 63(4): 407-418, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32592706

RESUMO

Bicuspid aortic valve (BAV) is the most common congenital cardiac malformation, frequently associated with aortopathies and valvulopathies. The congenital origin of BAV is suspected to impact the development of the disease in the adult life. During the last decade, a number of studies dealing with the embryonic development of congenital heart disease have significantly improved our knowledge on BAV etiology. They describe the developmental defects, at the molecular, cellular and morphological levels, leading to congenital cardiac malformations, including BAV, in animal models. These models consist of a spontaneous hamster and several mouse models with different genetic manipulations in genes belonging to a variety of pathways. In this review paper, we aim to gather information on the developmental defects leading to BAV formation in these animal models, in order to tentatively explain the morphogenetic origin of the spectrum of valve morphologies that characterizes human BAV. BAV may be the only defect resulting from gene manipulation in mice, but usually it appears as the less severe defect of a spectrum of malformations, most frequently affecting the cardiac outflow tract. The genes whose alterations cause BAV belong to different genetic pathways, but many of them are direct or indirectly associated with the NOTCH pathway. These molecular alterations affect three basic cellular mechanisms during heart development, i.e., endocardial-to-mesenchymal transformation, cardiac neural crest (CNC) cell behavior and valve cushion mesenchymal cell differentiation. The defective cellular functions affect three possible morphogenetic mechanisms, i.e., outflow tract endocardial cushion formation, outflow tract septation and valve cushion excavation. While endocardial cushion abnormalities usually lead to latero-lateral BAVs and septation defects to antero-posterior BAVs, alterations in cushion excavation may give rise to both BAV types. The severity of the original defect most probably determines the specific aortic valve phenotype, which includes commissural fusions and raphes. Based on current knowledge on the developmental mechanisms of the cardiac outflow tract, we propose a unified hypothesis of BAV formation, based on the inductive role of CNC cells in the three mechanisms of BAV development. Alterations of CNC cell behavior in three possible alternative key valvulogenic processes may lead to the whole spectrum of BAV.


Assuntos
Valva Aórtica/anormalidades , Doenças das Valvas Cardíacas/embriologia , Animais , Valva Aórtica/embriologia , Valva Aórtica/patologia , Modelos Animais de Doenças , Doenças das Valvas Cardíacas/genética , Doenças das Valvas Cardíacas/patologia , Humanos , Crista Neural
5.
Prog Cardiovasc Dis ; 63(4): 465-474, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32599028

RESUMO

The aortopathy associated with bicuspid aortic valve (BAV) is an epidemiologically relevant source of chronic and acute aortic disease (aneurysm and dissection). However, its pathogenesis is still the object of scientific uncertainties and debates. Indeed, the mechanisms determining the diseases of the ascending aorta in BAV patients are most likely complex and multifactorial, i.e. resulting from variable modes of interplay between genetic and hemodynamic factors. Although few scientific studies have so far taken into adequate account this complexity, leaving the precise sequence of pathogenetic events still undiscovered, the accumulated evidence from previous research approaches have at least brought about important insights. While genetic studies have so far identified variants relevant to either valve malformation or aortic complications (including those in the genes NOTCH1, TGFBR2, ACTA2, GATA5, NKX2.5, SMAD6, ROBO4), however each explaining not more than 5% of the study population, other investigations have thoroughly described both the flow features, with consequent forces acting on the arterial wall (including skewed flow jet direction, rotational flow, wall shear stress), and the main changes in the molecular and cellular wall structure (including extracellular matrix degradation, smooth muscle cell changes, oxidative stress, unbalance of TGF-ß signaling, aberrant endothelial-to-mesenchymal transition). All of this evidence, together with the recognition of the diverse phenotypes that the aortopathy can assume in BAV patients, holding possible prognostic significance, is reviewed in this chapter. The complex and multifaceted body of knowledge resulting from clinical and basic science studies on BAV aortopathy has the potential to importantly influence modes of clinical management of this disease in the near future.


Assuntos
Aorta/patologia , Valva Aórtica/anormalidades , Doenças das Valvas Cardíacas/complicações , Valva Aórtica/patologia , Doenças das Valvas Cardíacas/genética , Doenças das Valvas Cardíacas/patologia , Humanos
6.
J Card Surg ; 35(5): 1145-1147, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32293048

RESUMO

Caseous calcification of the mitral annulus (CCMA) is a very rare form of mitral annular calcification (MAC). CCMA accounts for 0.63% of all cases and 0.06-0.07% of the total population and usually seen in elderly and female patients. It mostly affects the posterior leaflet of the mitral valve. The pathogenesis of CCMA remains unclear. Hypercholesterolemia and the dissolution of lipid-laden macrophages may be implicated in liquefaction necrosis. CCMA is composed of a mixture of calcium, fatty acid, and cholesterol. The name "caseous" comes from the cheese-like or toothpaste-like consistency of the mass. Cardiac magnetic resonance imaging may help in differentiating MAC from CCMA and should perform. The first treatment option should be conservative treatment because of surgical complications of the procedure. We presented a case report which is about CCMA with preoperative and intraoperative robotic images.


Assuntos
Calcinose/diagnóstico por imagem , Calcinose/cirurgia , Doenças das Valvas Cardíacas/diagnóstico por imagem , Doenças das Valvas Cardíacas/cirurgia , Implante de Prótese de Valva Cardíaca/métodos , Valva Mitral/diagnóstico por imagem , Valva Mitral/cirurgia , Imagem Multimodal , Procedimentos Cirúrgicos Robóticos/métodos , Idoso , Calcinose/patologia , Evolução Fatal , Feminino , Doenças das Valvas Cardíacas/patologia , Humanos , Período Intraoperatório , Valva Mitral/patologia
7.
Int J Nanomedicine ; 15: 901-912, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32103945

RESUMO

Background: Aortic valve disease is the most common valvular heart disease leading to valve replacement. The efficacy of pharmacological therapy for aortic valve disease is limited by the high mechanical stress at the aortic valves impairing the binding rate. We aimed to identify nanoparticle coating with entire platelet membranes to fully mimic their inherent multiple adhesive mechanisms and target the sclerotic aortic valve of apolipoprotein E-deficient (ApoE-/-) mice based on their multiple sites binding capacity under high shear stress. Methods: Considering the potent interaction of platelet membrane glycoproteins with components present in sclerotic aortic valves, platelet membrane-coated nanoparticles (PNPs) were synthetized and the binding capacity under high shear stress was evaluated in vitro and in vivo. Results: PNPs demonstrated effectively adhering to von Willebrand factor, collagen and fibrin under shear stresses in vitro. In an aortic valve disease model established in ApoE-/- mice, PNPs exhibited good targeting to sclerotic aortic valves by mimicking platelet multiple adhesive mechanisms. Conclusion: PNPs could provide a promising platform for the molecular diagnosis and targeting treatment of aortic valve disease.


Assuntos
Plaquetas/citologia , Doenças das Valvas Cardíacas/tratamento farmacológico , Nanopartículas/química , Nanopartículas/metabolismo , Animais , Valva Aórtica/efeitos dos fármacos , Valva Aórtica/patologia , Apolipoproteínas E/genética , Plaquetas/química , Membrana Celular/química , Colágeno/metabolismo , Modelos Animais de Doenças , Fibrina/metabolismo , Cardiopatias Congênitas , Doenças das Valvas Cardíacas/patologia , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoE , Nanopartículas/uso terapêutico , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Esclerose , Estresse Mecânico , Fator de von Willebrand/metabolismo
8.
Medicine (Baltimore) ; 99(3): e18813, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32011489

RESUMO

INTRODUCTION: Pulmonary artery intimal sarcoma (PAIS) is a rare and highly aggressive tumor, and approximately 80% of pulmonary cases occur in the pulmonary trunk. We report herein a case of retrograde extension of the sarcoma to the pulmonary valve and right ventricle, which is an uncommon manifestation of this lethal tumor. PATIENT CONCERNS: A 41-year-old woman was initially diagnosed with pulmonary thromboembolism (PTE) and transferred to our hospital. DIAGNOSIS: Computed tomographic pulmonary angiography (CTPA) showed that there are low-density filling defects in both pulmonary arteries, and the patient was diagnosed with PTE. However, the ultrasonographers considered that the lesion is a space-occupying type that involves the right ventricular outflow tract and pulmonary valve instead of PTE. Postoperative pathology confirmed the diagnosis of PAIS. INTERVENTIONS: The patient underwent resection of pulmonary artery sarcoma and endarterectomy. OUTCOMES: During the follow-up via telephone 1 month after discharge, the patient reported to have been feeling well. CONCLUSION: Owing to the rarity of the disease and its non-specific clinical manifestations, approximately half of the PAIS cases are misdiagnosed or have a delayed diagnosis. Thus, improving our understanding of the disease and facilitating its early diagnosis are essential.


Assuntos
Neoplasias Cardíacas/diagnóstico , Artéria Pulmonar , Sarcoma/diagnóstico , Neoplasias Vasculares/diagnóstico , Adulto , Erros de Diagnóstico , Feminino , Neoplasias Cardíacas/patologia , Neoplasias Cardíacas/cirurgia , Doenças das Valvas Cardíacas/diagnóstico , Doenças das Valvas Cardíacas/patologia , Doenças das Valvas Cardíacas/cirurgia , Humanos , Embolia Pulmonar/diagnóstico , Valva Pulmonar , Sarcoma/patologia , Sarcoma/cirurgia , Neoplasias Vasculares/patologia , Neoplasias Vasculares/cirurgia
10.
J Card Surg ; 35(4): 897-900, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32092179

RESUMO

BACKGROUND AND AIMS: The optimal valve and prosthesis in patients with aortic valve infective endocarditis with annular abscess is controversial. If extensive annular defects occur after debridement, standard techniques are difficult; more complex aortic root replacement (ARR) or aortic valve translocation technique are inevitable. The Solo Smart stentless bioprosthesis is specially designed for supra-annular implantation without annular stitches. METHODS: Nineteen patients with active aortic valve infective endocarditis underwent aortic valve replacement in the past 3 years. Of these, we performed aortic valve replacement using the Solo Smart valve in four patients with extensive annular destruction and complex aortic root pathologies requiring reconstruction. RESULTS: Although more than two-thirds of the annular structure was missing after radical debridement of infected tissues, supra-annular aortic valve replacement with the Solo Smart valve could be performed successfully in all four patients. All patients are doing well without prosthetic valve dysfunction and/or recurrent infection. CONCLUSION: The supra-annular aortic valve replacement using the Solo Smart valve is considered to be a useful alternative to standard aortic valve replacement in patients complicated with extensive annular defect. It is a simple and technically less demanding alternative to ARR or aortic valve translocation technique.


Assuntos
Valva Aórtica/cirurgia , Bioprótese , Endocardite/cirurgia , Doenças das Valvas Cardíacas/cirurgia , Implante de Prótese de Valva Cardíaca/métodos , Procedimentos Cirúrgicos sem Sutura/métodos , Idoso , Valva Aórtica/patologia , Desbridamento , Feminino , Doenças das Valvas Cardíacas/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Stents , Resultado do Tratamento
11.
J Thorac Cardiovasc Surg ; 160(1): 47-57, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31982122

RESUMO

OBJECTIVE: Bicuspid aortic valve (BAV) represents 2 cusps oriented along a spectrum of equal (180°/180°) or unequal (150°/210°) leaflet surface area distribution along the aortic annular plane. We have taken the approach of respecting the native geometric orientation of the repaired BAV leaflets when creating the aortic neoroot during valve-sparing root reimplantation (VSRR) procedures. We investigated midterm outcomes with this 2-prong approach for VSRR in BAV syndrome. METHODS: Of 72 patients in a prospectively maintained BAV repair database, 68 met inclusion criteria: 36 patients had 180°/180° neoroot geometry, and 32 patients had 150°/210° orientation. A multivariate ordinal logistic mixed effects model was performed to study parameters associated with recurrent AI greater than 2+. RESULTS: Preoperative parameters were similar between 180°/180° and 150°/210° groups, except for greater incidence of AI 4+ in the latter (50.0% [n = 16] vs 8.3% [n = 3]; P < .001). Postoperatively, stroke, renal failure, reoperation for bleeding, and pacemaker rates were 0 in the entire cohort. In-hospital/30-day mortality in the entire cohort was 1.5% (n = 1). Multivariate ordinal logistic mixed effects model showed that preoperative AI greater than 3+ (odds ratio, 0.4; P = .46) and geometric orientation of the aortic neoroot (odds ratio, 3.8; P = .25) were not significantly associated with recurrence of AI greater than 2+. CONCLUSIONS: Respecting BAV geometry for VSRR neoroot creation yields excellent midterm outcomes and may minimize conjoint cusp leaflet stress that may occur in "forcing" a 150°/210° type I BAV into a 180°/180° neoroot.


Assuntos
Aorta , Valva Aórtica/anormalidades , Doenças das Valvas Cardíacas , Tratamentos com Preservação do Órgão , Reimplante , Adulto , Aorta/anatomia & histologia , Aorta/cirurgia , Valva Aórtica/patologia , Valva Aórtica/cirurgia , Insuficiência da Valva Aórtica/cirurgia , Feminino , Doenças das Valvas Cardíacas/patologia , Doenças das Valvas Cardíacas/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Tratamentos com Preservação do Órgão/efeitos adversos , Tratamentos com Preservação do Órgão/métodos , Tratamentos com Preservação do Órgão/estatística & dados numéricos , Complicações Pós-Operatórias , Estudos Retrospectivos
12.
Cardiovasc Pathol ; 46: 107194, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31982687

RESUMO

BACKGROUND: Celecoxib, a selective cyclooxygenase-2 inhibitor, was recently associated with increased incidence of aortic stenosis and found to produce a valvular calcification risk in vitro. Several cyclooxygenase-2 independent celecoxib derivatives have been developed and identified as possible therapies for inflammatory diseases due to their cadherin-11 inhibitory functions. Potential cardiovascular toxicities associated with these cyclooxygenase-2 independent celecoxib derivatives have not yet been investigated. Furthermore, the mechanism by which celecoxib produces valvular toxicity is not known. METHODS AND RESULTS: Celecoxib treatment produces a 2.8-fold increase in calcification in ex vivo porcine aortic valve leaflets and a more than 2-fold increase in calcification in porcine aortic valve interstitial cells cultured in osteogenic media. Its cyclooxygenase-2 independent derivative, 2,5-dimethylcelecoxib, produces a similar 2.5-fold increase in calcification in ex vivo leaflets and a 13-fold increase in porcine aortic valve interstitial cells cultured in osteogenic media. We elucidate that this offtarget effect depends on the presence of either of the two media components: dexamethasone, a synthetic glucocorticoid used for osteogenic induction, or cortisol, a natural glucocorticoid present at basal levels in the fetal bovine serum. In the absence of glucocorticoids, these inhibitors effectively reduce calcification. By adding glucocorticoids or hydrocortisone to a serum substitute lacking endogenous glucocorticoids, we show that dimethylcelecoxib conditionally induces a 3.5-fold increase in aortic valve calcification and osteogenic expression. Treatment with the Mitogen-activated protein kinase kinase inhibitor, U0126, rescues the offtarget effect, suggesting that celecoxib and dimethylcelecoxib conditionally augment Mitogen-activated protein kinase kinase/extracellular-signal-regulated kinase activity in the presence of glucocorticoids. CONCLUSION: Here we identify glucocorticoids as a possible source of the increased valvular calcification risk associated with celecoxib and its cyclooxygenase-2 independent derivatives. In the absence of glucocorticoids, these inhibitors effectively reduce calcification. Furthermore, the offtarget effects are not due to the drug's intrinsic properties as dual cyclooxygenase-2 and cadherin-11 inhibitors. These findings inform future design and development of celecoxib derivatives for potential clinical therapy.


Assuntos
Valva Aórtica/efeitos dos fármacos , Calcinose/induzido quimicamente , Celecoxib/toxicidade , Inibidores de Ciclo-Oxigenase 2/toxicidade , Dexametasona/toxicidade , Glucocorticoides/toxicidade , Doenças das Valvas Cardíacas/induzido quimicamente , Hidrocortisona/toxicidade , Osteogênese/efeitos dos fármacos , Pirazóis/toxicidade , Sulfonamidas/toxicidade , Animais , Valva Aórtica/metabolismo , Valva Aórtica/patologia , Caderinas/genética , Caderinas/metabolismo , Calcinose/genética , Calcinose/metabolismo , Calcinose/patologia , Celecoxib/análogos & derivados , Células Cultivadas , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Doenças das Valvas Cardíacas/genética , Doenças das Valvas Cardíacas/metabolismo , Doenças das Valvas Cardíacas/patologia , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Transdução de Sinais , Sus scrofa , Técnicas de Cultura de Tecidos
13.
Circulation ; 141(2): 132-146, 2020 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-31928435

RESUMO

BACKGROUND: Myxomatous valve degeneration (MVD) involves the progressive thickening and degeneration of the heart valves, leading to valve prolapse, regurgitant blood flow, and impaired cardiac function. Leukocytes composed primarily of macrophages have recently been detected in myxomatous valves, but the timing of the presence and the contributions of these cells in MVD progression are not known. METHODS: We examined MVD progression, macrophages, and the valve microenvironment in the context of Marfan syndrome (MFS) using mitral valves from MFS mice (Fbn1C1039G/+), gene-edited MFS pigs (FBN1Glu433AsnfsX98/+), and patients with MFS. Additional histological and transcriptomic evaluation was performed by using nonsyndromic human and canine myxomatous valves, respectively. Macrophage ontogeny was determined using MFS mice transplanted with mTomato+ bone marrow or MFS mice harboring RFP (red fluorescent protein)-tagged C-C chemokine receptor type 2 (CCR2) monocytes. Mice deficient in recruited macrophages (Fbn1C1039G/+;Ccr2RFP/RFP) were generated to determine the requirements of recruited macrophages to MVD progression. RESULTS: MFS mice recapitulated histopathological features of myxomatous valve disease by 2 months of age, including mitral valve thickening, increased leaflet cellularity, and extracellular matrix abnormalities characterized by proteoglycan accumulation and collagen fragmentation. Diseased mitral valves of MFS mice concurrently exhibited a marked increase of infiltrating (MHCII+, CCR2+) and resident macrophages (CD206+, CCR2-), along with increased chemokine activity and inflammatory extracellular matrix modification. Likewise, mitral valve specimens obtained from gene-edited MFS pigs and human patients with MFS exhibited increased monocytes and macrophages (CD14+, CD64+, CD68+, CD163+) detected by immunofluorescence. In addition, comparative transcriptomic evaluation of both genetic (MFS mice) and acquired forms of MVD (humans and dogs) unveiled a shared upregulated inflammatory response in diseased valves. Remarkably, the deficiency of monocytes was protective against MVD progression, resulting in a significant reduction of MHCII macrophages, minimal leaflet thickening, and preserved mitral valve integrity. CONCLUSIONS: All together, our results suggest sterile inflammation as a novel paradigm to disease progression, and we identify, for the first time, monocytes as a viable candidate for targeted therapy in MVD.


Assuntos
Doenças das Valvas Cardíacas/patologia , Síndrome de Marfan/patologia , Monócitos/metabolismo , Animais , Quimiocina CCL2/metabolismo , Modelos Animais de Doenças , Progressão da Doença , Cães , Matriz Extracelular/metabolismo , Fibrilina-1/genética , Fibrilina-1/metabolismo , Doenças das Valvas Cardíacas/complicações , Doenças das Valvas Cardíacas/metabolismo , Antígenos Comuns de Leucócito/metabolismo , Macrófagos/citologia , Macrófagos/metabolismo , Síndrome de Marfan/complicações , Síndrome de Marfan/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Valva Mitral/metabolismo , Valva Mitral/fisiopatologia , Monócitos/citologia , Suínos
14.
Arterioscler Thromb Vasc Biol ; 40(3): 638-655, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31893948

RESUMO

OBJECTIVE: Although often studied independently, little is known about how aortic valve endothelial cells and valve interstitial cells interact collaborate to maintain tissue homeostasis or drive valve calcific pathogenesis. Inflammatory signaling is a recognized initiator of valve calcification, but the cell-type-specific downstream mechanisms have not been elucidated. In this study, we test how inflammatory signaling via NFκB (nuclear factor κ-light-chain enhancer of activated B cells) activity coordinates unique and shared mechanisms of valve endothelial cells and valve interstitial cells differentiation during calcific progression. Approach and Results: Activated NFκB was present throughout the calcific aortic valve disease (CAVD) process in both endothelial and interstitial cell populations in an established mouse model of hypercholesterolemia-induced CAVD and in human CAVD. NFκB activity induces endothelial to mesenchymal transformation in 3-dimensional cultured aortic valve endothelial cells and subsequent osteogenic calcification of transformed cells. Similarly, 3-dimensional cultured valve interstitial cells calcified via NFκB-mediated osteogenic differentiation. NFκB-mediated endothelial to mesenchymal transformation was directly demonstrated in vivo during CAVD via genetic lineage tracking. Genetic deletion of NFκB in either whole valves or valve endothelium only was sufficient to prevent valve-specific molecular and cellular mechanisms of CAVD in vivo despite the persistence of a CAVD inducing environment. CONCLUSIONS: Our results identify NFκB signaling as an essential molecular regulator for both valve endothelial and interstitial participation in CAVD pathogenesis. Direct demonstration of valve endothelial cell endothelial to mesenchymal transformation transmigration in vivo during CAVD highlights a new cellular population for further investigation in CAVD morbidity. The efficacy of valve-specific NFκB modulation in inhibiting hypercholesterolemic CAVD suggests potential benefits of multicell type integrated investigation for biological therapeutic development and evaluation for CAVD.


Assuntos
Valva Aórtica/metabolismo , Calcinose/metabolismo , Diferenciação Celular , Células Endoteliais/metabolismo , Doenças das Valvas Cardíacas/metabolismo , NF-kappa B/metabolismo , Osteogênese , Animais , Valva Aórtica/patologia , Calcinose/etiologia , Calcinose/patologia , Células Cultivadas , Microambiente Celular , Modelos Animais de Doenças , Células Endoteliais/patologia , Doenças das Valvas Cardíacas/etiologia , Doenças das Valvas Cardíacas/genética , Doenças das Valvas Cardíacas/patologia , Humanos , Hipercolesterolemia/complicações , Hipercolesterolemia/genética , Hipercolesterolemia/metabolismo , Quinase I-kappa B/genética , Quinase I-kappa B/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , NF-kappa B/genética , Fatores de Transcrição NFATC/genética , Fatores de Transcrição NFATC/metabolismo , Receptores de LDL/genética , Receptores de LDL/metabolismo , Transdução de Sinais , Fator de Transcrição RelA/genética , Fator de Transcrição RelA/metabolismo
15.
Res Vet Sci ; 128: 99-106, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31765842

RESUMO

Myxomatous mitral valve disease (MMVD) is the single most important acquired cardiovascular disease of the dog. Much is known about the cellular changes and the contribution of activated myofibroblasts (valve interstitial cells (aVICs) to the valve extra-cellular matrix remodelling characteristic of the disease. However, little is known on how aVIC survival might contribute to disease pathogenesis. This study examined the temporal (disease severity-dependent) and spatial distribution of aVICs in MMVD valves, the expression of a range of apoptosis-related genes in cultured VICs from both normal (quiescent VIC (qVIC) and diseased (aVIC) valves, and the differential effects of doxorubicin treatment, as a trigger of apoptosis, on expression of the same genes. Activated myofibroblasts were identified in normal valves at the valve base only (the area closest to the annulus), and then became more numerous and apparent along the valve length as the disease progressed, with evidence of cell survival at the valve base. There were no significant differences in basal gene expression comparing qVICs and aVICs for CASP3, FAS, BID, BAX, BCL2, CASP8, DDIAS, XIAP and BIRC5. After doxorubicin treatment (2 mM) for 8 h there was significant difference (P < .05) in the expression of BID, BCL2, DDIAS, and CASP8, but when assessed for interactions using a mixed model ANOVA only CASP8 was significantly different because of treatment (P < .05). These data suggest aVIC survival in MMVD valves may be a consequence of heightened resistance of aVICs to apoptosis, but would require confirmation examining expression of the relevant proteins.


Assuntos
Apoptose/fisiologia , Doenças do Cão/patologia , Doenças das Valvas Cardíacas/veterinária , Valva Mitral/patologia , Miofibroblastos/fisiologia , Animais , Apoptose/genética , Doenças do Cão/metabolismo , Cães , Doxorrubicina/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Doenças das Valvas Cardíacas/metabolismo , Doenças das Valvas Cardíacas/patologia , Valva Mitral/citologia , Valva Mitral/metabolismo
16.
Ann Thorac Surg ; 109(1): e25-e27, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31207247

RESUMO

Percutaneous transcatheter intervention for aortic regurgitation secondary to implantation of a continuous-flow left ventricular assist device remains challenging, because of the minimal global experience with these procedures. Two treatment options are available: transcatheter aortic valve replacement, which is not always feasible when a dilated aortic annulus is present, and percutaneous aortic valve occlusion. We report a successful percutaneous closure of the aortic valve using an oversized Amplatzer patent foramen ovale multifenestrated device (St Jude Medical, Saint Paul, MN) to treat aortic regurgitation associated with dilated aortic annulus in a patient with a continuous-flow left ventricular assist device.


Assuntos
Insuficiência da Valva Aórtica/cirurgia , Valva Aórtica/cirurgia , Coração Auxiliar , Complicações Pós-Operatórias/cirurgia , Idoso , Valva Aórtica/patologia , Procedimentos Cirúrgicos Cardíacos/métodos , Dilatação Patológica , Doenças das Valvas Cardíacas/patologia , Doenças das Valvas Cardíacas/cirurgia , Humanos , Masculino
17.
Nat Genet ; 52(1): 40-47, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31844321

RESUMO

Valvular heart disease is observed in approximately 2% of the general population1. Although the initial observation is often localized (for example, to the aortic or mitral valve), disease manifestations are regularly observed in the other valves and patients frequently require surgery. Despite the high frequency of heart valve disease, only a handful of genes have so far been identified as the monogenic causes of disease2-7. Here we identify two consanguineous families, each with two affected family members presenting with progressive heart valve disease early in life. Whole-exome sequencing revealed homozygous, truncating nonsense alleles in ADAMTS19 in all four affected individuals. Homozygous knockout mice for Adamts19 show aortic valve dysfunction, recapitulating aspects of the human phenotype. Expression analysis using a lacZ reporter and single-cell RNA sequencing highlight Adamts19 as a novel marker for valvular interstitial cells; inference of gene regulatory networks in valvular interstitial cells positions Adamts19 in a highly discriminatory network driven by the transcription factor lymphoid enhancer-binding factor 1 downstream of the Wnt signaling pathway. Upregulation of endocardial Krüppel-like factor 2 in Adamts19 knockout mice precedes hemodynamic perturbation, showing that a tight balance in the Wnt-Adamts19-Klf2 axis is required for proper valve maturation and maintenance.


Assuntos
Proteínas ADAMTS/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Doenças das Valvas Cardíacas/etiologia , Proteínas ADAMTS/genética , Animais , Família , Feminino , Doenças das Valvas Cardíacas/patologia , Humanos , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/metabolismo , Masculino , Camundongos , Camundongos Knockout , Linhagem , Análise de Célula Única , Via de Sinalização Wnt
18.
Pediatr Cardiol ; 41(2): 350-360, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31858201

RESUMO

Aortic root size and cusp fusion pattern have been related to disease outcomes in bicuspid aortic valve (BAV). This study seeks to characterize symmetry of the aortic sinuses in adult and pediatric BAV patients and its relationship to valvulopathy and root aortopathy. Aortic sinus-to-commissure (S-C) lengths were measured on cardiac MRI of adult and pediatric BAV patients with right-and-left coronary (RL) or right-and-non-coronary (RN) leaflet fusion and tricuspid aortic valve (TAV) controls. Coefficient of variance (CoV) of S-C lengths was calculated to quantify sinus asymmetry, or eccentricity. BAV cohort included 149 adults (48 ± 15 years) and 51 children (15 ± 5 years). TAV cohort included 40 adults (60 ± 13 years) and 20 children (15 ± 5 years). In adult and pediatric BAV patients, the non-fused aortic sinus was larger than either fused sinus. In RL fusion, the non-coronary S-C distance was larger than right or left S-C distances in adults (n = 121, p < 0.001) and larger than the right S-C distance in children (n = 41, p = 0.013). Sinus eccentricity (CoV) in BAV patients was higher than in TAV patients (p < 0.001) and did not correlate with age (p = 0.12). CoV trended higher in RL adults with aortic regurgitation (AR) compared to those without AR (p = 0.081), but was lower in RN adults with AR than without AR (p = 0.006). CoV did not correlate to root Z scores (p = 0.06-0.55) or ascending aortic (AAo) Z scores in adults (p = 0.45-0.55) but correlated negatively to AAo Z score in children (p = 0.005-0.03). Most adult and pediatric BAV patients with RL and RN leaflet fusion demonstrate eccentric dominance of the non-fused aortic sinus irrespective of age. The degree of eccentricity varies with valve dysfunction and BAV phenotype but does not relate to the degree of aortic root dilatation, nor does eccentricity correlate with ascending aorta dilatation in adults.


Assuntos
Valva Aórtica/anormalidades , Doenças das Valvas Cardíacas/patologia , Seio Aórtico/patologia , Adolescente , Adulto , Aorta/diagnóstico por imagem , Aorta/patologia , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/patologia , Criança , Feminino , Doenças das Valvas Cardíacas/etiologia , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Seio Aórtico/diagnóstico por imagem , Adulto Jovem
19.
Arterioscler Thromb Vasc Biol ; 40(3): 656-669, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31852220

RESUMO

OBJECTIVE: Retinoic acid (RA) is a ligand for nuclear receptors that modulate gene transcription and cell differentiation. Whether RA controls ectopic calcification in humans is unknown. We tested the hypothesis that RA regulates osteogenic differentiation of human arterial smooth muscle cells and aortic valvular interstitial cells that participate in atherosclerosis and heart valve disease, respectively. Approach and Results: Human cardiovascular tissue contains immunoreactive RAR (RA receptor)-a retinoid-activated nuclear receptor directing multiple transcriptional programs. RA stimulation suppressed primary human cardiovascular cell calcification while treatment with the RAR inhibitor AGN 193109 or RARα siRNA increased calcification. RA attenuated calcification in a coordinated manner, increasing levels of the calcification inhibitor MGP (matrix Gla protein) while decreasing calcification-promoting TNAP (tissue nonspecific alkaline phosphatase) activity. Given that nuclear receptor action varies as a function of distinct ligand structures, we compared calcification responses to cyclic retinoids and the acyclic retinoid peretinoin. Peretinoin suppressed human cardiovascular cell calcification without inducing either secretion of APOC3 (apolipoprotein-CIII), which promotes atherogenesis, or reducing CYP7A1 (cytochrome P450 family 7 subfamily A member 1) expression, which occurred with cyclic retinoids all-trans RA, 9-cis RA, and 13-cis RA. Additionally, peretinoin did not suppress human femur osteoblast mineralization, whereas all-trans RA inhibited osteoblast mineralization. CONCLUSIONS: These results establish retinoid regulation of human cardiovascular calcification, provide new insight into mechanisms involved in these responses, and suggest selective retinoid modulators, like acyclic retinoids may allow for treating cardiovascular calcification without the adverse effects associated with cyclic retinoids.


Assuntos
Valva Aórtica/efeitos dos fármacos , Colesterol 7-alfa-Hidroxilase/metabolismo , Doenças das Valvas Cardíacas/prevenção & controle , Músculo Liso Vascular/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Receptores do Ácido Retinoico/agonistas , Retinoides/farmacologia , Calcificação Vascular/prevenção & controle , Valva Aórtica/metabolismo , Valva Aórtica/patologia , Apolipoproteína C-III/genética , Apolipoproteína C-III/metabolismo , Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação ao Cálcio/metabolismo , Artérias Carótidas/efeitos dos fármacos , Artérias Carótidas/metabolismo , Artérias Carótidas/patologia , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Células Cultivadas , Colesterol 7-alfa-Hidroxilase/genética , Vasos Coronários/efeitos dos fármacos , Vasos Coronários/metabolismo , Vasos Coronários/patologia , Proteínas da Matriz Extracelular/genética , Proteínas da Matriz Extracelular/metabolismo , Doenças das Valvas Cardíacas/genética , Doenças das Valvas Cardíacas/metabolismo , Doenças das Valvas Cardíacas/patologia , Humanos , Isotretinoína/farmacologia , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Receptores do Ácido Retinoico/genética , Receptores do Ácido Retinoico/metabolismo , Retinoides/toxicidade , Transdução de Sinais , Tretinoína/farmacologia , Calcificação Vascular/genética , Calcificação Vascular/metabolismo , Calcificação Vascular/patologia
20.
Innovations (Phila) ; 14(6): 577-580, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31739722

RESUMO

Pulmonary fibroelastomas are a rare primary cardiac tumor with less than 50 cases reported in the literature to date. We performed a minimally invasive valve-sparing tumor resection through a left anterior mini-incision (LAMI). The procedure was performed without cardiac arrest or aortic cross clamp, expediting postoperative recovery and allowing for an uncomplicated discharge on postoperative day 5. LAMI is a safe and reliable alternative to median sternotomy for patients requiring interventions on the right ventricular outflow tract and main pulmonary artery, including pulmonary fibroelastoma resection and pulmonary valve replacement when needed.


Assuntos
Fibroma/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Artéria Pulmonar/cirurgia , Insuficiência da Valva Pulmonar/cirurgia , Procedimentos Cirúrgicos Cardíacos/tendências , Ponte Cardiopulmonar/normas , Cateterismo/métodos , Ecocardiografia/métodos , Feminino , Artéria Femoral/cirurgia , Fibroma/patologia , Doenças das Valvas Cardíacas/patologia , Doenças das Valvas Cardíacas/cirurgia , Humanos , Imagem por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Insuficiência da Valva Pulmonar/diagnóstico por imagem , Insuficiência da Valva Pulmonar/patologia , Toracotomia/métodos , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA