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1.
Catheter Cardiovasc Interv ; 101(3): 520-527, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36740230

RESUMEN

OBJECTIVES: We sought to investigate whether a novel, fast-pullback, high-frequency optical coherence tomography (HF-OCT) imaging system enables data acquisition with a reduced amount of contrast agents while retaining the same qualitative and quantitative lesion assessment to conventional OCT. BACKGROUND: The increased amount of administered contrast agents is a major concern when performing intracoronary OCT. METHODS: The present study is a single-center, prospective, observational study including 10 patients with stable coronary artery disease. A total of 28 individual coronary arteries were assessed by both fast-pullback HF-OCT and by conventional OCT. RESULTS: The contrast volume used in each OCT run for the HF-OCT system was significantly lower than for the conventional OCT system (5.0 ± 0.0 mL vs. 7.8 ± 0.7 mL, respectively, with a mean difference of -2.84 [95% confidence interval [CI]: -3.10 to -2.58]). No significant difference was found in the median value of the clear image length between the two OCT systems (74 mm [interquartile range [IQR]; 63, 81], 74 mm [IQR; 71, 75], p = 0.89). Fast-pullback HF-OCT showed comparable measurements to conventional OCT, including minimum lumen area (3.27 ± 1.53 mm2 vs. 3.21 ± 1.53 mm2 , p = 0.27), proximal reference area (7.03 ± 2.28 mm2 vs. 7.03 ± 2.34 mm2 , p = 0.96), and distal reference area (5.93 ± 1.96 mm2 vs. 6.03 ± 2.02 mm2 , p = 0.23). Qualitative OCT findings were comparable between the fast-pullback HF-OCT runs and conventional OCT with respect to identifying lipid-rich plaques, calcifications, layered plaques, macrophages, and cholesterol crystals. CONCLUSION: With the fast pullback function of a novel HF-OCT imaging system, we acquired OCT images using a significantly lower amount of contrast volume while retaining a comparable qualitative and quantitative lesion assessment to conventional OCT.


Asunto(s)
Enfermedad de la Arteria Coronaria , Placa Aterosclerótica , Humanos , Tomografía de Coherencia Óptica/métodos , Medios de Contraste , Estudios Prospectivos , Resultado del Tratamiento , Reproducibilidad de los Resultados , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/patología , Vasos Coronarios/diagnóstico por imagen , Vasos Coronarios/patología
2.
Acta Cardiol Sin ; 39(2): 266-276, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36911548

RESUMEN

Background: Optical coherence tomography (OCT) is currently used as a guide for percutaneous coronary intervention (PCI), however its clinical benefit in comparison with intravascular ultrasound (IVUS) remains unclear in patients with acute coronary syndrome (ACS). Objectives: The purpose of this study was to evaluate the clinical efficacy of OCT-guided PCI in comparison with IVUS-guided PCI in patients with ACS. Methods: The study participants comprised 280 consecutive ACS patients who underwent primary PCI for de novo culprit lesions under OCT or IVUS guidance. Results: Compared with the IVUS-guided group, the OCT-guided group had lower Killip classification (p < 0.001) and lower creatinine level at baseline (0.80 ± 0.37 mg/dl vs. 1.13 ± 1.29 mg/dl, p = 0.004). Fluoroscopy time and total procedure time were significantly shorter in the OCT-guided group than in the IVUS-guided group (32 ± 13 min vs. 41 ± 19 min, p < 0.001, and 98 ± 39 min vs. 127 ± 47 min, p = 0.002, respectively). The major adverse cardiovascular event-free survival curves were similar between the OCT- and IVUS-guided groups after adjusting for clinical background using propensity score (log-rank p = 0.328). Conclusions: After adjusting for clinical background, OCT-guided PCI could provide comparable clinical outcomes to IVUS-guided PCI in patients with ACS. Shorter fluoroscopy time and total procedure time with OCT may reduce patient radiation exposure and also improve hospital workflow.

3.
J Vasc Surg ; 75(5): 1553-1560.e1, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-34998941

RESUMEN

OBJECTIVE: Acute type A aortic dissection (ATAAD) is a critical disease presenting with disseminated intravascular coagulation (DIC). However, the relationship between the degree of DIC and false lumen conditions remains unclear. In the present study, we evaluated the degree of preoperative DIC and the outcomes of ATAAD treatment. METHODS: A total of 124 patients with ATAAD (70 men and 54 women) treated from January 2012 to January 2020 were included in the present study. The correlation between the preoperative Japanese Association for Acute Medicine (JAAM) DIC score and the false lumen diameter and length, measured using preoperative computed tomography, was examined retrospectively. The correlations were calculated using liner regression analysis. The level of statistical significance was set at P < .05. RESULTS: The patients were divided into two groups: a low JAAM DIC score group and a high JAAM DIC score group. The preoperative JAAM DIC scores in the high- and low-score groups were 4.8 ± 1.2 and 1.7 ± 2.3, respectively (P < .001). The 5-year survival rates and aortic event-free rates in the low-score group were favorable compared with the high-score group; however, the differences were not statistically significant (80.8% vs 54.5%, P = .065; 63.9% vs 59.8%, P = .15, respectively). The false lumen diameter in the ascending aorta was greater in the high-score group than that in the low-score group (P < .05). The JAAM DIC score correlated significantly with the ascending false lumen diameter and the dissection length (r = 0.32 and P < .001; r = 0.29 and P = .001, respectively). A high JAAM DIC score was associated with communicating-type ATAAD (P < .05). CONCLUSIONS: Our results suggest that high preoperative JAAM DIC scores are associated with a large false lumen and communicating-type ATAAD.


Asunto(s)
Disección Aórtica , Coagulación Intravascular Diseminada , Disección Aórtica/complicaciones , Disección Aórtica/diagnóstico por imagen , Disección Aórtica/cirugía , Coagulación Intravascular Diseminada/diagnóstico , Coagulación Intravascular Diseminada/etiología , Femenino , Humanos , Masculino , Estudios Retrospectivos
4.
Ann Vasc Surg ; 84: 187-194, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35257923

RESUMEN

BACKGROUND: Type B aortic dissection (TBAD) is treated with thoracic endovascular aortic repair (TEVAR). However, the optimal timing of the surgical intervention remains unclear. We aimed to investigate whether the timing of TEVAR impacts aortic remodeling. METHODS: Forty-three patients with TBAD (31 men and 12 women) who had undergone surgical intervention with TEVAR between January 2014 and June 2021 were retrospectively evaluated. The relationship between the timing of TEVAR and success of aortic remodeling was assessed using linear regression analysis. Successful aortic remodeling was defined by a reduction of diametric ratio (false lumen/aorta) at 3 points (thoracic region, thoracoabdominal region, and abdominal region) and measured using computed tomography both pre- and post-operatively. The level of statistical significance was set at P < 0.05. RESULTS: The timing of TEVAR after symptom onset was defined as early (≤14 days, n = 27, group E) or late (≥15 days, n = 16, group L). The median duration from symptom onset to TEVAR in groups E and L were 3 days (interquartile range [IQR], 1.5-6 days) and 196 days (IQR, 89.8-252.3 days), respectively (P < 0.001). Patent type, rupture, malperfusion, and continuous pain were present preoperatively in 82%, 3.7%, 14.8%, and 33.3% of patients in group E, respectively, and in 37.5%, 0%, 6.3%, and 0% of patients in group L, respectively. In group E, thoracic aortic diameter and false luminal thickness were decreased significantly from pre- to post-operation (36.9 ± 12.4 vs. 35 ± 12.7 mm, P = 0.03; 13.6 ± 6.2 vs. 3.4 ± 4.5 mm, P < 0.001, respectively). Whereas, thoracic aortic diameter significantly increased, and false luminal thickness did not significantly change pre- and post-operation in group L (32.7 ± 9.5 vs. 37 ± 12.8 mm, P = 0.041; 9.1 ± 4.5 vs. 7.5 ± 9.5 mm, P = 0.4, respectively). CONCLUSIONS: Our results suggest that early intervention for TBAD with TEVAR increases the success of aortic remodeling.


Asunto(s)
Aneurisma de la Aorta Torácica , Disección Aórtica , Implantación de Prótesis Vascular , Procedimientos Endovasculares , Disección Aórtica/diagnóstico por imagen , Disección Aórtica/cirugía , Aneurisma de la Aorta Torácica/diagnóstico por imagen , Aneurisma de la Aorta Torácica/cirugía , Implantación de Prótesis Vascular/efectos adversos , Procedimientos Endovasculares/efectos adversos , Femenino , Humanos , Masculino , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Remodelación Vascular
5.
Nucleic Acids Res ; 48(18): e108, 2020 10 09.
Artículo en Inglés | MEDLINE | ID: mdl-32941625

RESUMEN

The auxin-inducible degron (AID) system enables rapid depletion of target proteins within the cell by applying the natural auxin IAA. The AID system is useful for investigating the physiological functions of essential proteins; however, this system generally requires high dose of auxin to achieve effective depletion in vertebrate cells. Here, we describe a super-sensitive AID system that incorporates the synthetic auxin derivative 5-Ad-IAA and its high-affinity-binding partner OsTIR1F74A. The super-sensitive AID system enabled more than a 1000-fold reduction of the AID inducer concentrations in chicken DT40 cells. To apply this system to various mammalian cell lines including cancer cells containing multiple sets of chromosomes, we utilized a single-step method where CRISPR/Cas9-based gene knockout is combined with insertion of a pAID plasmid. The single-step method coupled with the super-sensitive AID system enables us to easily and rapidly generate AID-based conditional knockout cells in a wide range of vertebrate cell lines. Our improved method that incorporates the super-sensitive AID system and the single-step method provides a powerful tool for elucidating the roles of essential genes.


Asunto(s)
Técnicas de Inactivación de Genes/métodos , Ácidos Indolacéticos/química , Proteínas de Plantas/genética , Proteolisis , Animales , Sistemas CRISPR-Cas , Línea Celular , Pollos , Humanos , Oryza/metabolismo
6.
Catheter Cardiovasc Interv ; 97(1): E12-E18, 2021 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-32329140

RESUMEN

OBJECTIVE: The purpose of this experimental bench test was to compare stent deformation, obstruction of stent struts at a jailed side branch (SB) ostium, and stent strut malapposition between SB inflation using proximal balloon edge dilation (PBED) technique and SB inflation using conventional balloon dilation in repetitive-proximal optimizing technique (re-POT) sequence. BACKGROUND: The second proximal optimizing technique (POT) procedure in the re-POT sequence might increase obstruction of stent struts at a jailed SB ostium, because deformation of stent cells at the main branch (MB) occurred during SB inflation for opening the SB ostium. METHODS: A fractal coronary bifurcation bench model made of flexible urethane was used, and crossover single-stent implantation (Xience Sierra, Abbott Vascular, Santa Clara, CA, n = 12) was performed from the MB with the re-POT sequence. During the re-POT sequence, the jailing rate at the SB ostium assessed by videoscopy was compared between SB inflation using PBED technique (PBED group, n = 6) and SB inflation using conventional balloon dilation (conventional group, n = 6). RESULTS: The jailing rate after the second POT procedure tended to be lower in the PBED group than in the conventional group (26 ± 12% vs. 34 ± 8%, p = .211), and the change in the jailing rate during the second POT procedure was significantly smaller in the PBED group than in the conventional group (4.8 ± 5.3% vs. 11.6 ± 3.5%, p = .026). CONCLUSIONS: In the re-POT sequence, the PBED technique with a short balloon for SB inflation might minimize worsening of the jailing rate at the SB ostium during the second POT procedure.


Asunto(s)
Angioplastia Coronaria con Balón , Vasos Coronarios , Angioplastia Coronaria con Balón/efectos adversos , Vasos Coronarios/diagnóstico por imagen , Vasos Coronarios/cirugía , Dilatación , Stents , Resultado del Tratamiento
7.
Chem Pharm Bull (Tokyo) ; 69(3): 265-270, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33642474

RESUMEN

Peptide drug leads possess unusual structural features that allow them to exert their unique biological activities and ideal physicochemical properties. In particular, these peptides often have D-amino acids, and therefore the absolute configurations of the component amino acids have to be elucidated during the structural determination of newly isolated peptide drug leads. Recently, we developed the highly sensitive labeling reagents D/L-FDVDA and D/L-FDLDA for the structural determination of the component amino acids in peptides. In an LC-MS-based structural study of peptides, these reagents enabled us to detect infinitesimal amounts of amino acids derived from mild degradative analysis of the samples. Herein, we firstly report the improved LC-MS protocols for the highly sensitive analyses of amino acids. Second, two new labeling reagents were synthesized and their detection sensitivities evaluated. These studies increase our understanding of the structural basis of these highly sensitive labeling reagents, and should provide opportunities for future on-demand structural modifications of the reagents to enhance their hydrophobicity, stability, and affinity for applications to specialized HPLC columns.


Asunto(s)
Aminoácidos/análisis , Péptidos/química , Secuencia de Aminoácidos , Técnicas Biosensibles , Cromatografía Líquida de Alta Presión , Interacciones Hidrofóbicas e Hidrofílicas , Indicadores y Reactivos/química , Estabilidad Proteica , Sensibilidad y Especificidad , Coloración y Etiquetado , Estereoisomerismo , Espectrometría de Masas en Tándem
8.
Int Heart J ; 62(5): 1106-1111, 2021 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-34544984

RESUMEN

The proximal optimizing technique (POT) -proximal balloon edge dilation (PBED) sequence for side branch (SB) dilatation with cross-over single-stent implantation decreases both strut obstruction at the SB ostium and stent deformation at the main branch (MB).The purpose of this experimental bench test was to assess the impact of stent design on stent deformation, obstruction by stent struts at a jailed SB ostium, and stent strut malapposition in the POT-PBED sequence.Fractal coronary bifurcation bench models (60- and 80-degree angles) were used, and crossover single-stent implantation (3-link stent: XIENCE Sierra, Abbott Vascular, Santa Clara, CA, n = 10; 2-link stent: Synergy, Boston Scientific, Marlborough, MA, n = 10) was performed from the MB using the POT-PBED sequence. Jailing rates at the SB ostium, stent deformation, and stent strut malapposition of the bifurcation segment were assessed using videoscopy and optical coherence tomography.After SB dilatation using the PBED technique, jailing rates at the SB ostium and stent deformation did not differ significantly between the two types of stents. Conversely, the rate of malapposed struts of the bifurcation segment after the PBED procedure was significantly lower with 3-link stents than with 2-link stents for both 60- and 80-degree angles (60-degree angle: 4.3% ± 4.4% versus 22.0% ± 11.1%, P = 0.044; 80-degree angle: 20.8% ± 15.1% versus 57.2% ± 17.0%, P < 0.001, respectively).In the POT-PBED sequence, 3-link stents might be a preferable coronary bifurcation stent, maintaining a jailed SB ostium while significantly reducing stent strut malapposition of the bifurcation segment when compared with 2-link stents.


Asunto(s)
Angioplastia Coronaria con Balón/métodos , Intervención Coronaria Percutánea/instrumentación , Diseño de Prótesis/efectos adversos , Stents/efectos adversos , Angioplastia Coronaria con Balón/estadística & datos numéricos , Vasos Coronarios/anatomía & histología , Humanos , Modelos Anatómicos , Modelos Cardiovasculares , Stents/estadística & datos numéricos , Stents/tendencias , Tomografía de Coherencia Óptica
9.
Nat Chem Biol ; 14(3): 299-305, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29355850

RESUMEN

The phytohormone auxin indole-3-acetic acid (IAA) regulates nearly all aspects of plant growth and development. Despite substantial progress in our understanding of auxin biology, delineating specific auxin response remains a major challenge. Auxin regulates transcriptional response via its receptors, TIR1 and AFB F-box proteins. Here we report an engineered, orthogonal auxin-TIR1 receptor pair, developed through a bump-and-hole strategy, that triggers auxin signaling without interfering with endogenous auxin or TIR1/AFBs. A synthetic, convex IAA (cvxIAA) hijacked the downstream auxin signaling in vivo both at the transcriptomic level and in specific developmental contexts, only in the presence of a complementary, concave TIR1 (ccvTIR1) receptor. Harnessing the cvxIAA-ccvTIR1 system, we provide conclusive evidence for the role of the TIR1-mediated pathway in auxin-induced seedling acid growth. The cvxIAA-ccvTIR1 system serves as a powerful tool for solving outstanding questions in auxin biology and for precise manipulation of auxin-mediated processes as a controllable switch.


Asunto(s)
Proteínas de Arabidopsis/química , Proteínas F-Box/química , Regulación de la Expresión Génica de las Plantas , Ácidos Indolacéticos/química , Receptores de Superficie Celular/química , Arabidopsis/química , Arabidopsis/genética , Cruzamientos Genéticos , Cinética , Mutación , Reguladores del Crecimiento de las Plantas , Raíces de Plantas , Unión Proteica , Ingeniería de Proteínas , Plantones , Transducción de Señal , Transgenes
10.
Acta Cardiol Sin ; 36(1): 16-23, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31903004

RESUMEN

BACKGROUND: The purpose of this study was to investigate the clinical significance of elevated plasma high-sensitivity troponin T (hs-TnT) in the chronic phase in patients with stable angina pectoris (SAP) who underwent a successful percutaneous coronary intervention (PCI). METHODS: This study enrolled 158 consecutive SAP patients who underwent routine follow-up coronary angiography 9 months after a successful PCI with the implantation of a second-generation drug-eluting stent. Patients with previous coronary artery bypass graft and renal dysfunction were excluded. Patients were divided into two groups according to hs-TnT plasma level at follow-up: elevated hs-TnT (≥ 0.015 ng/ml) group and non-elevated hs-TnT group. RESULTS: Among the 158 subjects, 42 had an elevated hs-TnT level at follow-up. The elevated hs-TnT group had a significantly higher rate of any coronary lesion (in-stent restenosis and de novo lesions) in follow-up CAG (coronary angiography) than the non-elevated group (28.6% vs. 10.3%, p < 0.05). Multivariate analysis also showed that hs-TnT elevation was independently associated with the presence of significant coronary stenosis in the chronic phase (odds ratio: 3.99, 95% confidence interval: 1.38 to 11.53). The best cut-off value of the hs-TnT level at 9 months after a successful PCI to predict the presence of significant coronary stenosis was 0.016 ng/ml (sensitivity: 50.0%; specificity: 82.1%; area under the receiver operating characteristic curve: 0.67). CONCLUSIONS: hs-TnT elevation was independently associated with the presence of coronary stenosis in the chronic phase in SAP patients with successful PCI. Routine measurement of hs-TnT in the chronic phase may be useful to refine the risk of patients after PCI.

11.
Catheter Cardiovasc Interv ; 93(1): E17-E23, 2019 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-30244506

RESUMEN

OBJECTIVES: The purpose of this study was to compare the stent deformation, obstruction of stent struts at a jailed side branch (SB) ostium, and stent strut malapposition after a repetitive proximal optimizing technique (re-POT) sequence between bifurcation lesions with and without stent links at SB ostia in ex vivo experimental setting. METHODS: A flexible urethane coronary bifurcation bench model was used, and crossover single stent implantation was performed from main branch (MB) with re-POT sequence. Under videoscope observation, presence (link group, n = 12) or absence (no-link group, n = 12) of stent link at distal semicircle of SB ostium was intentionally set, and rewiring was performed through distal cell in four different stent platforms. RESULTS: There were no significant differences in the rate of malapposed struts and in SB jailing ratio after the re-POT sequence between the link and no-link groups. SB jailing ratio increased significantly from 8.0% to 9.6% during the second POT procedure (P < 0.001). SB jailing ratio after the second POT procedure differed among stent platforms. CONCLUSIONS: The presence of a stent link at an SB ostium was not associated with a rate of malapposed struts and SB jailing ratio after the re-POT sequence. SB jailing ratio was significantly increased after second POT procedure, but was different among stent platforms. The Xience stent might minimize the change of SB jailing ratio and be suitable for coronary bifurcation stenting using re-POT sequence.


Asunto(s)
Angioplastia Coronaria con Balón/instrumentación , Vasos Coronarios/diagnóstico por imagen , Endoscopía , Stents , Tomografía de Coherencia Óptica , Angioplastia Coronaria con Balón/efectos adversos , Modelos Anatómicos , Modelos Cardiovasculares , Imagen Multimodal , Valor Predictivo de las Pruebas , Diseño de Prótesis , Uretano , Grabación en Video
12.
Circ J ; 83(12): 2452-2459, 2019 11 25.
Artículo en Inglés | MEDLINE | ID: mdl-31645508

RESUMEN

BACKGROUND: Healed plaques are identified as a layered pattern with optical coherence tomography (OCT) imaging, but the exact relationship between healed plaques and the development of significant coronary stenosis in stable angina pectoris (SAP) is not fully understood.Methods and Results:A retrospective clinincal study investigated the OCT characteristics of culprit lesions of SAP patients (n=205), and a prospective study examined the histopathological characteristics of layered plaque in directional coronary atherectomy (DCA) samples (42 samples from 18 SAP patients). In the retrospective study, layered plaque was observed in 36.6% of the SAP culprit lesions. Compared with patients with non-layered plaque, male sex and smoking were more frequent, and HbA1c level was significantly higher in the patients with layered plaque (81.3% vs. 65.9%, P<0.05; 62.7% vs. 41.8%, P<0.05; 6.6±1.3% vs. 6.2±1.0%, P<0.05, respectively). Furthermore, layered plaque was accompanied by higher plaque vulnerability and smaller minimal lumen area. In the histopathological study, the layered plaques had a significantly higher rate of intramural thrombus and macrophages infiltration than non-layered plaques (75.0% vs. 14.3%, P<0.05; 75.0% vs. 38.1%, P<0.05, respectively). CONCLUSIONS: Healed plaque containing intramural thrombus is identified as layered plaque by OCT, and was frequently observed, even in SAP patients. Intramural thrombus might play an important role in the development of coronary plaque with a high degree of stenosis in SAP patients.


Asunto(s)
Angina Estable , Enfermedad de la Arteria Coronaria , Estenosis Coronaria , Trombosis Coronaria , Vasos Coronarios , Placa Aterosclerótica , Tomografía de Coherencia Óptica , Anciano , Anciano de 80 o más Años , Angina Estable/diagnóstico por imagen , Angina Estable/epidemiología , Angina Estable/patología , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/epidemiología , Enfermedad de la Arteria Coronaria/patología , Estenosis Coronaria/diagnóstico por imagen , Estenosis Coronaria/epidemiología , Estenosis Coronaria/patología , Trombosis Coronaria/diagnóstico por imagen , Trombosis Coronaria/epidemiología , Trombosis Coronaria/patología , Vasos Coronarios/diagnóstico por imagen , Vasos Coronarios/patología , Femenino , Humanos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Prevalencia , Estudios Prospectivos , Estudios Retrospectivos
13.
J Physiol ; 596(18): 4427-4442, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-30062729

RESUMEN

KEY POINTS: We examined the mechanisms underlying the positive effect of preconditioning contractions (PCs) on the recovery of muscle force after damaging eccentric contractions (ECCs). The mechanisms underlying the immediate force decrease after damaging ECCs differ from those causing depressed force with a few days' delay, where reactive oxygen species (ROS) produced by invading immune cells play an important causative role. PCs counteracted the delayed onset force depression and this could be explained by prevention of immune cell invasion, which resulted in decreased myeloperoxidase-mediated ROS production, hence avoiding cell membrane disruption, calpain activation and degenerative changes in myosin and actin molecules. ABSTRACT: Preconditioning contractions (PCs) have been shown to result in markedly improved contractile function during the recovery periods after muscle damage from eccentric contractions (ECCs). Here, we examined the mechanisms underlying the beneficial effect of PCs with a special focus on the myofibrillar function. Rat medial gastrocnemius muscles were exposed to 100 repeated damaging ECCs in situ and excised immediately (recovery 0, REC0) or after 4 days (REC4). PCs with 10 repeated non-damaging ECCs were applied 2 days before the damaging ECCs. PCs improved in situ maximal isometric torque at REC4. Skinned muscle fibres were used to directly assess changes in myofibrillar function. PCs prevented the damaging ECC-induced depression in maximum Ca2+ -activated force at REC4. PCs also prevented the following damaging ECC-induced effects at REC4: (i) the reduction in myosin heavy chain and actin content; (ii) calpain activation; (iii) changes in redox homeostasis manifested as increased expression levels of malondialdehyde-protein adducts, NADPH oxidase 2, superoxide dismutase 2 and catalase, and activation of myeloperoxidase (MPO); (iv) infiltration of immune cells and loss of cell membrane integrity. Additionally, at REC0, PCs enhanced the expression levels of heat shock protein (HSP) 70, HSP25, and αB-crystallin in the myofibrils and prevented the increased mRNA levels of granulocyte-macrophage colony-stimulating factor and interleukin-6. In conclusion, PCs prevent the delayed force depression after damaging ECCs by an HSP-dependent inhibition of degenerative changes in myosin and actin molecules caused by myeloperoxidase-induced membrane lysis and subsequent calpain activation, which were triggered by an inflammatory reaction with immune cells invading damaged muscles.


Asunto(s)
Contracción Isométrica , Miofibrillas/fisiología , Estrés Oxidativo , Actinas/metabolismo , Animales , Calcio/metabolismo , Calpaína/metabolismo , Células Cultivadas , Proteínas de Choque Térmico/metabolismo , Interleucina-6/metabolismo , Macrófagos/fisiología , Masculino , Miofibrillas/metabolismo , Miofibrillas/patología , Cadenas Pesadas de Miosina/metabolismo , NADPH Oxidasas/metabolismo , Neutrófilos/fisiología , Peroxidasa/metabolismo , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismo , Superóxido Dismutasa/metabolismo
14.
Plant Cell Physiol ; 59(8): 1538-1544, 2018 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-29986114

RESUMEN

Auxin regulates diverse aspects of plant growth and development through induction of the interaction between TRANSPORT INHIBITOR RESPONSE 1/AUXIN SIGNALING F-BOX proteins (TIR1/AFBs) and AUXIN/INDOLE-3-ACETIC ACID (Aux/IAA) co-receptor proteins and the subsequent transcriptional regulation. The artificial control of endogenous auxin signaling should enable the precise delineation of auxin-mediated biological events as well as the agricultural application of auxin. To this end, we previously developed a synthetic auxin-receptor pair that consists of 5-(3-methoxyphenyl)-IAA (convexIAA, cvxIAA) and the engineered TIR1 whose phenylalanine at position 79 in the auxin-binding pocket is substituted to glycine (TIR1F79G) (concaveTIR1, ccvTIR1). This synthetic auxin-receptor pair works orthogonally to natural auxin signaling in transgenic plants harboring the engineered TIR1 by exogenous application of 5-(3-methoxyphenyl)-IAA, and has potential to be utilized as novel agricultural/horticultural tools. In the present study, we report an improved version of the synthetic cvxIAA-ccvTIR1 pair such that synthetic IAA can act at lower concentrations. Using a yeast two-hybrid system, we screened various 5-substituted IAAs and identified 5-adamantyl-IAA, named pico_cvxIAA, which mediates interaction of TIR1F79G and IAA3 proteins at a 1,000-fold lower concentration than the original version, 5-(3-methoxyphenyl)-IAA. Furthermore, we found that TIR1F79A interacts with IAA3 protein in the presence of picomolar concentrations of 5-adamantyl-IAA, 10,000-fold lower than our prototype version of the cvxIAA-ccvTIR1 pair. In addition, pull-down assays confirmed that 5-adamantyl-IAA mediates in vitro interaction of TIR1F79A and IAA7-DII peptides at lower concentrations. The improved synthetic IAA-TIR1 pair with high affinity would be beneficial for basic science as well as for practical use in agriculture/horticulture.


Asunto(s)
Proteínas de Arabidopsis/metabolismo , Proteínas F-Box/metabolismo , Ácidos Indolacéticos/metabolismo , Receptores de Superficie Celular/metabolismo , Proteínas Nucleares/metabolismo , Unión Proteica
15.
Acta Cardiol Sin ; 34(2): 124-129, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-29643697

RESUMEN

BACKGROUND: To evaluate the neointimal conditions of everolimus-eluting stents (EESs) implanted in culprit lesions of patients with acute coronary syndrome (ACS) compared with stable angina pectoris (SAP) using optical coherence tomography (OCT). EESs are second-generation drug-eluting stents that have recently been shown to be useful in patients with ACS as well as in patients with SAP. However, few studies have analyzed the intra-stent conditions of EESs that can lead to favorable results in such ACS lesions. METHODS: We evaluated 41 ACS patients with EES implantation (age, 66.7 ± 10.3 years) and 59 SAP patients enrolled as controls (age, 68.3 ± 10.7 years). OCT examinations were performed after 9 months of follow-up after stent implantation, and the condition of the neointimal coverage over every stent strut was assessed in 1-mm intervals. In addition, neointimal thickness (NIT) over each strut was measured and tissue characteristics were examined. RESULTS: There was no significant difference in mean NIT between the ACS (90.8 ± 88.2 mm) and SAP (87.3 ± 74.2 mm, p = 0.11) group. The rate of uncovered struts was significantly lower in the ACS group (11.5%) than in the SAP group (12.5%, p = 0.03). Neointimal tissue characteristics were also similar between groups. CONCLUSIONS: Vascular responses after EES implantation differed significantly between ACS and SAP lesions using OCT. However, these differences were considered small in clinical terms. Our OCT data support the favorable results of patients with EES implantation at mid-term follow-up, even in those with ACS.

17.
Int Heart J ; 58(1): 131-133, 2017 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-28077820

RESUMEN

A 68-year-old female with acute coronary syndrome was transferred to our hospital. Emergency coronary angiography showed 90% stenosis with severe calcification in the proximal right coronary artery (RCA). Intravascular ultrasound (IVUS) images were obtained and showed circumferential heavy calcification without any evidence of plaque rupture. Optical frequency domain imaging (OFDI) images were obtained in the RCA lesion 3 days after the initial coronary angiography. A cavity of plaque rupture in the calcified plaque by using OFDI was observed in the lesion, which could not be recognized by IVUS. Necrotic tissue was observed frequently in heavy calcified lesions and was usually hidden behind calcification. Judging from the OFDI images in this case, the thin fibrous cap over the necrotic tissue even if surrounded by calcification was disrupted and might have caused the acute coronary syndrome. However, necrotic tissue surrounded by calcification is generally recognized as calcified plaque in OFDI images because discrimination between necrotic tissue and calcification is based on the border characteristics (low intensity with diffuse border: necrotic tissue, low intensity with sharp border: calcification). Superficial residual necrotic tissue not yet replaced completely by calcification might cause plaque rupture and thus, result in acute coronary syndrome. In fact, there is a variety of OFDI and optical coherence tomography (OCT) characteristics in calcified plaque, such as relatively high intensity without attenuation or very low intensity with attenuation. Residual necrotic tissue within calcification could pose a problem in OCT/OFDI plaque evaluation.


Asunto(s)
Síndrome Coronario Agudo/diagnóstico por imagen , Placa Aterosclerótica/diagnóstico por imagen , Tomografía de Coherencia Óptica , Calcificación Vascular/diagnóstico por imagen , Anciano , Femenino , Humanos
18.
Circulation ; 131(12): 1054-60, 2015 Mar 24.
Artículo en Inglés | MEDLINE | ID: mdl-25712205

RESUMEN

BACKGROUND: More than 20% of patients presenting to the cardiac catheterization laboratory with angina have no angiographic evidence of coronary artery disease. Despite a "normal" angiogram, these patients often have persistent symptoms, recurrent hospitalizations, a poor functional status, and adverse cardiovascular outcomes, without a clear diagnosis. METHODS AND RESULTS: In 139 patients with angina in the absence of obstructive coronary artery disease (no diameter stenosis >50%), endothelial function was assessed; the index of microcirculatory resistance, coronary flow reserve, and fractional flow reserve were measured; and intravascular ultrasound was performed. There were no complications. The average age was 54.0±11.4 years, and 107 (77%) were women. All patients had at least some evidence of atherosclerosis based on an intravascular ultrasound examination of the left anterior descending artery. Endothelial dysfunction (a decrease in luminal diameter of >20% after intracoronary acetylcholine) was present in 61 patients (44%). Microvascular impairment (an index of microcirculatory resistance ≥25) was present in 29 patients (21%). Seven patients (5%) had a fractional flow reserve ≤0.80. A myocardial bridge was present in 70 patients (58%). Overall, only 32 patients (23%) had no coronary explanation for their angina, with normal endothelial function, normal coronary physiological assessment, and no myocardial bridging. CONCLUSIONS: The majority of patients with angina in the absence of obstructive coronary artery disease have occult coronary abnormalities. A comprehensive invasive assessment of these patients at the time of coronary angiography can be performed safely and provides important diagnostic information that may affect treatment and outcomes.


Asunto(s)
Angina de Pecho/diagnóstico por imagen , Angiografía Coronaria/normas , Enfermedad de la Arteria Coronaria , Circulación Coronaria/fisiología , Reserva del Flujo Fraccional Miocárdico/fisiología , Ultrasonografía Intervencional/normas , Adulto , Anciano , Velocidad del Flujo Sanguíneo/fisiología , Angiografía Coronaria/métodos , Femenino , Humanos , Masculino , Microcirculación/fisiología , Persona de Mediana Edad , Ultrasonografía Intervencional/métodos
19.
Int Heart J ; 57(6): 763-765, 2016 Dec 02.
Artículo en Inglés | MEDLINE | ID: mdl-27818479

RESUMEN

A 62-year-old man with a family history of coronary artery disease and a history of smoking, diabetes and dyslipidemia was admitted to our hospital with chest pain from acute myocardial infarction. Emergent coronary angiography was performed with intervention to a mid-right coronary occlusion with drug-eluting stent implantation. Optical coherence tomography (OCT) visualized well-apposed stent struts and no remarkable tissue protrusion, stent underexpansion, malapposition, edge dissection, and hematoma. Immediately after OCT imaging, a coronary angiogram showed a filling defect surrounded by contrast medium at the site of the stented lesion. OCT imaging was performed again and a low backscattering protrusion suggestive of white thrombus in the coronary lumen was clearly visualized in OCT imaging. We performed thrombus aspiration immediately after OCT imaging. Aspirated thrombi were off-white in color. We made a diagnosis of early-onset heparin-induced-thrombocytopenia (HIT) due to thrombus formation within the stent and positive HIT antibodies. OCT in the acute phase of stent thrombosis allowed us to promptly identify the main causative mechanisms of early stent thrombosis.


Asunto(s)
Trombosis Coronaria/diagnóstico por imagen , Stents Liberadores de Fármacos , Oclusión de Injerto Vascular/diagnóstico por imagen , Heparina/efectos adversos , Trombocitopenia/complicaciones , Tomografía de Coherencia Óptica , Trombosis Coronaria/etiología , Trombosis Coronaria/cirugía , Fibrinolíticos/efectos adversos , Oclusión de Injerto Vascular/etiología , Oclusión de Injerto Vascular/cirugía , Humanos , Masculino , Persona de Mediana Edad , Trombocitopenia/inducido químicamente , Trombocitopenia/diagnóstico
20.
Circ J ; 79(3): 607-12, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25746545

RESUMEN

BACKGROUND: Coronary arterial segments distal to the severely stenotic lesion sometimes shrink as a result of decreased coronary flow. Pathological studies have shown that vessel shrinkage is accompanied by folding of the internal elastic membrane (IEM). A peri-medial high-echoic band (PHB) by intravascular ultrasound (IVUS) may represent folding of the IEM and therefore detect chronically shrunken coronary segments that have potential to enlarge subsequently. METHODS AND RESULTS: IVUS imaging of the distal reference segments was performed in 27 patients after stenting. PHB was defined as a high-echoic band observed at the luminal side of the media. Serial (baseline and 9 months) changes in minimal lumen diameter (LD) were compared between those with (PHB group) and without PHB (non-PHB group). During follow-up, LD increased significantly in PHB group (1.2±0.3 vs. 1.7±0.5 mm, P=0.001) but not in the non-PHB group (2.0±0.7 vs. 2.1±0.7 mm, P=NS). Late lumen gain (LLG) was observed in 16 of the 27 (59%) lesions. Lesions with LLG showed a trend toward smaller baseline lumen cross-sectional area and significantly higher prevalence of PHB (88% vs. 18%, P=0.007). By multivariable logistic regression analysis, PHB was the only IVUS predictor of LLG. CONCLUSIONS: Presence of PHB on IVUS predicts chronic enlargement of the coronary segments distal to the stented lesion.


Asunto(s)
Angiografía Coronaria , Estenosis Coronaria/diagnóstico por imagen , Anciano , Estenosis Coronaria/cirugía , Diagnóstico por Imagen de Elasticidad/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Intervención Coronaria Percutánea , Prohibitinas , Stents , Ultrasonografía Intervencional/métodos
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