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1.
Int Heart J ; 56(6): 639-43, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26549390

RESUMO

Patients with periodontal disease exhibit exacerbated atherosclerosis, aortic stiffness, or vascular endothelial dysfunction. However, in a recent scientific statement, the American Heart Association noted that neither has periodontal disease been proven to cause atherosclerotic vascular disease nor has the treatment of periodontal disease been proven to prevent atherosclerotic vascular disease. Therefore, the aim of the present study was to examine the correlation between periodontal condition and arteriosclerosis in patients with coronary artery disease (CAD), which is usually accompanied by systemic arteriosclerosis.We measured levels of gingival crevicular fluid lactoferrin (GCF-Lf) and α1-antitrypsin (GCF-AT) in 72 patients (67 ± 8 years, 56 men) with CAD. Furthermore, we evaluated the maximum intima-media thickness (max IMT) and plaque score of the carotid arteries as well as brachial-ankle pulse wave velocity (baPWV) and flow-mediated dilation (FMD) of the brachial artery, each of which is a parameter for determining arteriosclerosis status. The average level of GCF-Lf was 0.29 ± 0.36 µg/mL and that of GCF-AT was 0.31 ± 0.66 µg/mL, with significant correlation between the two (r = 0.701, P < 0.001). No significant difference in GCF-Lf and GCF-AT levels was observed between patients with single-, double-, and triple-vessel CAD. There were no significant correlations between the arteriosclerosis parameters (ie, max IMT, plaque score, baPWV, and FMD) and GCF-Lf or GCF-AT.No correlation between the GCF biomarkers and the severity of arteriosclerosis was detected. This result may suggest that worsening of the periodontal condition assessed by GCF biomarkers is not a major potential risk factor for arteriosclerosis.


Assuntos
Aterosclerose , Doença da Artéria Coronariana , Lactoferrina/metabolismo , Doenças Periodontais , alfa 1-Antitripsina/metabolismo , Idoso , Índice Tornozelo-Braço/métodos , Aterosclerose/diagnóstico , Aterosclerose/epidemiologia , Aterosclerose/metabolismo , Aterosclerose/fisiopatologia , Biomarcadores/metabolismo , Espessura Intima-Media Carotídea , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Periodontais/epidemiologia , Doenças Periodontais/metabolismo , Análise de Onda de Pulso/métodos , Distribuição Aleatória , Medição de Risco/métodos , Fatores de Risco , Índice de Gravidade de Doença , Estatística como Assunto
2.
J Vasc Surg ; 51(1): 155-64, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19954921

RESUMO

OBJECTIVE: There is an increasing need for vascular grafts in the field of surgical revascularization. However, smaller vascular grafts made from synthetic biomaterials, particularly those <5 mm in diameter, are associated with a high incidence of thrombosis. Fibroin is a biodegradable protein derived from silk. Silk fibroin from Bombyx mori provides an antithrombotic surface and serves as a scaffold for various cell types in tissue engineering. We evaluated the potential of fibroin to generate a vascular prosthesis for small arteries. METHODS: A small vessel with three layers was woven from silk fibroin thread. These fibroin-based grafts (1.5 mm diameter, 10 mm length) were implanted into the abdominal aorta of 10- to 14-week-old male Sprague-Dawley rats by end-to-end anastomosis. Polytetrafluoroethylene (PTFE)-based grafts were used as the control. To investigate the origin of the cells in the neointima and media, bone marrow transplantation was performed from green fluorescent protein (GFP) rats to wild-type rats. RESULTS: The patency of fibroin grafts at 1 year after implantation was significantly higher than that of PTFE grafts (85.1% vs 30%, P < .01). Endothelial cells and smooth muscle cells (SMCs) migrated into the fibroin graft early after implantation and became organized into endothelial and medial layers, as determined by anti-CD31 and anti-alpha-smooth muscle actin immunostaining. The total number of SMCs increased 1.6-fold from 1 month to 3 months. Vasa vasorum also formed in the adventitia. Sirius red staining of the fibroin grafts revealed that the content of collagen significantly increased at 1 year after implantation, with a decrease in fibroin content. GFP-positive cells contributed to organization of a smooth muscle layer. CONCLUSIONS: Small-diameter fibroin-based vascular grafts have excellent long-term patency. Bone marrow-derived cells contribute to vascular remodeling after graft implantation. Fibroin might be a promising material to engineer vascular prostheses for small arteries.


Assuntos
Implantes Absorvíveis , Aorta Abdominal/cirurgia , Implante de Prótese Vascular/instrumentação , Prótese Vascular , Fibroínas , Grau de Desobstrução Vascular , Actinas/metabolismo , Animais , Aorta Abdominal/diagnóstico por imagem , Aorta Abdominal/metabolismo , Aortografia , Células da Medula Óssea/metabolismo , Transplante de Medula Óssea , Movimento Celular , Colágeno/metabolismo , Células Endoteliais/metabolismo , Proteínas de Fluorescência Verde/genética , Masculino , Teste de Materiais , Modelos Animais , Miócitos de Músculo Liso/metabolismo , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Politetrafluoretileno , Desenho de Prótese , Ratos , Ratos Sprague-Dawley , Ratos Transgênicos , Fatores de Tempo , Ultrassonografia Doppler em Cores
3.
J Atheroscler Thromb ; 27(12): 1299-1309, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32101838

RESUMO

AIM: Synthetic vascular grafts are widely used in surgical revascularization, mainly for medium- to large-sized vessels. However, synthetic grafts smaller than 6 mm in diameter are associated with a high incidence of thrombosis. In this study, we evaluated silk fibroin, a major protein of silk, with high biocompatibility and biodegradability, as a useful material for extremely-small-diameter vascular grafts. METHODS: A small-sized (0.9 mm inner diameter) graft was braided from a silk fibroin thread. The right carotid arteries of 8- to 14-week-old male C57BL/6 mice were cut at the midpoint, and fibroin grafts (5- to 7-mm in length) were transplanted using a cuff technique with polyimide cuffs. The grafts were harvested at different time points and analyzed histologically. RESULTS: CD31+ endothelial cells had already started to proliferate at 2 weeks after implantation. At 4 weeks, neointima had formed with α-smooth muscle actin+ cells, and the luminal surface was covered with CD31+endothelial cells. Mac3+ macrophages were accumulated in the grafts. Graft patency was confirmed at up to 6 months after implantation. CONCLUSION: This mouse model of arterial graft implantation enables us to analyze the remodeling process and biocompatibility of extremely-small-diameter vascular grafts. Biodegradable silk fibroin might be applicable for further researches using genetically modified mice.


Assuntos
Implantes Absorvíveis , Materiais Biocompatíveis/química , Prótese Vascular , Fibroínas/química , Animais , Implante de Prótese Vascular , Proliferação de Células , Células Endoteliais/citologia , Masculino , Camundongos Endogâmicos C57BL , Grau de Desobstrução Vascular
4.
J Med Invest ; 64(1.2): 64-67, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28373630

RESUMO

Although Lp(a) have been thought to be a cardiovascular risk factor, it is unclear whether lowering Lp(a) levels reduces the risk of cardiovascular diseases. No pharmacological agents which selectively reduce serum Lp(a) levels, and Lp(a) is present in primate but absent in common laboratory animals such as mice and pigs. In the present study we used transgenic mice of human Lp(a) and tested effect a novel Lp(a) lowering drug D-47 on neointima formation after vascular injury. D-47 successfully decreased plasma levels of Lp(a) and possibly inhibited neointima formation in Lp(a) transgenic mice. The results indicate that we can modulate plasma Lp(a) levels by pharmacologic agents and inhibit atherogenic properties of Lp(a) by reducing plasma levels of Lp(a). J. Med. Invest. 64: 64-67, February, 2017.


Assuntos
Éteres de Hidroxibenzoatos/farmacologia , Hipolipemiantes/farmacologia , Lipoproteína(a)/antagonistas & inibidores , Neointima/tratamento farmacológico , Pirrolidinonas/farmacologia , Lesões do Sistema Vascular/tratamento farmacológico , Animais , Artéria Femoral/efeitos dos fármacos , Artéria Femoral/lesões , Artéria Femoral/patologia , Humanos , Lipoproteína(a)/sangue , Lipoproteína(a)/genética , Masculino , Camundongos , Camundongos Transgênicos , Neointima/sangue , Neointima/patologia , Polietilenoglicóis/farmacologia , Polivinil/farmacologia , Proteínas Recombinantes/sangue , Proteínas Recombinantes/genética , Lesões do Sistema Vascular/sangue , Lesões do Sistema Vascular/patologia
6.
Front Cell Dev Biol ; 2: 19, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25364726

RESUMO

Bone marrow-derived cells (BMCs) are considered to be a major source of mesenchymal stem cells (MSCs) in adults and are known to be effective in periodontal tissue regeneration. However, whether endogenous BMCs are involved in periodontal tissue repair process is uncertain. We therefore created periodontal tissue defects in the buccal alveolar bone of mandibular first molars in bone marrow chimeric mice, and immunohistochemically examined the expression of stromal cell derived factor-1 (SDF-1) and the mobilization of BMCs. We found that SDF-1 expression was increased around the defects at as early as 1 week after injury and that BMCs were mobilized to the defects, while GFP+/CD45+ were rarely observed. Fluorescence-activated cell sorting (FACS) analysis demonstrated that the number of platelet-derived growth factor receptor (pdgfr) α+/Sca-1+ (PαS) cells in the bone marrow decreased after injury. Taken together, these results suggest that BMCs are mobilized to the periodontal tissue defects. Recruitment of BMCs, including a subset of MSCs could be a new target of periodontal treatment.

7.
Biomed Pharmacother ; 63(10): 781-6, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19906506

RESUMO

Impairment of cardiac function in cardiomyopathy has been postulated to be related to decreased blood flow and increased collagen synthesis. Administration of growth factors was reported to attenuate left ventricular (LV) remodeling and dysfunction in animal models of dilated cardiomyopathy. We previously reported that ONO-1301, a synthetic prostacyclin agonist with thromboxane-synthase inhibitory activity, promotes production of hepatocyte growth factor and vascular endothelial growth factor from various cell types and ameliorate ischemia-induced LV dysfunction in mice and pigs. We evaluated therapeutic efficacy of ONO-1301 in the Syrian hamster (TO-2), a model of genetically determined dilated cardiomyopathy. Either vehicle or a slow releasing form of ONO-1301 (ONO-1301-PLGA, 10mg/kg/3 weeks) was administered subcutaneously every 3 weeks to TO-2 hamsters from 24 to 32 weeks of age (n=12 for each group). Age-matched F1B hamsters were used as a control. Plasma concentration of HGF was elevated in ONO-1301-PLGA group (p<0.05). Echocardiographic study demonstrated that LV fractional shortening was significantly improved in the ONO-1301-PLGA group (25+/-4%, p<0.01) compared with that in the vehicle group (19+/-2%). Cardiac fibrosis was significantly reduced by ONO-1301-PLGA (p<0.05) as determined by Azan-Mallory staining. Capillary density of left ventricle was markedly reduced in TO-2 hamsters. ONO-1301-PLGA significantly increased capillary density in TO-2 group (p<0.05). ONO-1301 improved LV dysfunction and reduced cardiac fibrosis in the hamster model of dilated cardiomyopathy. ONO-1301 might hold a therapeutic potential in the treatment of dilated cardiomyopathy.


Assuntos
Cardiomiopatia Dilatada/tratamento farmacológico , Inibidores Enzimáticos/farmacologia , Piridinas/farmacologia , Disfunção Ventricular Esquerda/tratamento farmacológico , Animais , Cardiomiopatia Dilatada/fisiopatologia , Cricetinae , Preparações de Ação Retardada , Modelos Animais de Doenças , Portadores de Fármacos/química , Inibidores Enzimáticos/administração & dosagem , Fibrose , Ácido Láctico/química , Masculino , Miocárdio/patologia , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Piridinas/administração & dosagem , Tromboxano-A Sintase/antagonistas & inibidores , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/fisiopatologia
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