RESUMEN
BACKGROUND: The incidence and mortality of aortic dissection (AD) are increasing. In pathological studies, macrophages, T lymphocytes and dendritic cells were found in the tunica media of the aorta. Acetaldehyde dehydrogenase 2 (ALDH2) gene polymorphisms are associated with a high incidence of hypertension in Asian populations. However, there is no clear evidence of the relationship between ALDH2 and aortic dissection in Asians. The aim of this study was to investigate the incidence of aortic dissection in different ALDH2 genotypes and explore changes in the vasculature. MATERIALS AND METHODS: Three-week-old male mice were administered freshly prepared ß-aminopropionitrile solution dissolved in drinking water (1 g/kg/d) for 28 days to induce TAD. An animal ultrasound imaging system was used to observe the formation of arterial dissection and changes in cardiac function. Subsequently, mice were euthanized by cervical dislocation. The aortas were fixed for HE staining and EVG staining to observe aortic elastic fiber tears and pseudoluma formation under a microscope. RESULTS: Knockout of ALDH2 mitigated ß-aminopropionitrile-induced TAD formation in animal studies. Ultrasound results showed that ALDH2 knockout reduced the degree of ascending aortic widening and the incidence of aortic dissection rupture. Pathological sections of multiple aortic segments showed that the protective effect of ALDH2 knockout was observed in not only the ascending aorta but also the aortic arch and descending aorta. The expression levels of genes related to NK CD56bright cells, Th17 cells, T cells and T helper cells were decreased in ALDH2 knockout mice treated with ß-aminopropionitrile for 28 days. CONCLUSION: ALDH2 knockout protects against aortic dissection by altering the inflammatory response and immune response and protecting elastic fibers.
Asunto(s)
Aldehído Deshidrogenasa Mitocondrial/metabolismo , Aneurisma de la Aorta Torácica , Disección Aórtica , Rotura de la Aorta , Agua Potable , Aminopropionitrilo , Disección Aórtica/inducido químicamente , Disección Aórtica/diagnóstico por imagen , Disección Aórtica/genética , Animales , Modelos Animales de Enfermedad , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones NoqueadosRESUMEN
BACKGROUND: Cardiac resident macrophages are self-maintaining and originate from embryonic hematopoiesis. After myocardial infarction, cardiac resident macrophages are responsible for the efficient clearance and degradation of apoptotic cardiomyocytes (efferocytosis). This process is required for inflammation resolution and tissue repair; however, the underlying molecular mechanisms remain unknown. Therefore, we aimed to identify the mechanisms of the continued clearance and degradation of phagolysosomal cargo by cardiac resident macrophages during myocardial infarction. METHODS: Multiple transgenic mice such as Lgmn-/-, LgmnF/F; LysMCre, LgmnF/F; Cx3cr1CreER, LgmnF/F; LyveCre, and cardiac macrophage Lgmn overexpression by adenovirus gene transfer were used to determine the functional significance of Lgmn in myocardial infarction. Immune cell filtration and inflammation were examined by flow cytometry and quantitative real-time polymerase chain reaction. Moreover, legumain (Lgmn) expression was analyzed by immunohistochemistry and quantitative real-time polymerase chain reaction in the cardiac tissues of patients with ischemic cardiomyopathy and healthy control subjects. RESULTS: We identified Lgmn as a gene specifically expressed by cardiac resident macrophages. Lgmn deficiency resulted in a considerable exacerbation in cardiac function, accompanied by the accumulation of apoptotic cardiomyocytes and a reduced index of in vivo efferocytosis in the border area. It also led to decreased cytosolic calcium attributable to defective intracellular calcium mobilization. Furthermore, the formation of LC3-II-dependent phagosome around secondary-encountered apoptotic cardiomyocytes was disabled. In addition, Lgmn deficiency increased infiltration of MHC-IIhigh CCR2+ macrophages and the enhanced recruitment of MHC-IIlow CCR2+ monocytes with downregulation of the anti-inflammatory mediators, interleukin-10, and transforming growth factor-ß and upregulationof the proinflammatory mediators interleukin-1ß, tumor necrosis factor-α, interleukin-6, and interferon-γ. CONCLUSIONS: Our results directly link efferocytosis to wound healing in the heart and identify Lgmn as a significant link between acute inflammation resolution and organ function.
Asunto(s)
Infarto del Miocardio , Miocitos Cardíacos , Animales , Calcio/metabolismo , Cisteína Endopeptidasas , Humanos , Inflamación/metabolismo , Macrófagos/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Infarto del Miocardio/patología , Miocitos Cardíacos/metabolismoRESUMEN
Extended left ventricular septal myectomy remains the gold standard for the treatment of hypertrophic obstructive cardiomyopathy (HOCM) with refractory symptoms. On the basis of traditional modified transaortic Morrow myectomy, we innovatively performed a minimally invasive, video-assisted single-port thoracotomy through the right infra-axillary region. Our procedure can provide good visualization of the left ventricular outflow tract and hypertrophic ventricular septum for accurate resection. It also ensures optimal exposure of the mitral valve in the presence of complex mitral subvalvular structures.
Asunto(s)
Procedimientos Quirúrgicos Cardíacos , Cardiomiopatía Hipertrófica , Procedimientos Quirúrgicos Cardíacos/métodos , Cardiomiopatía Hipertrófica/cirugía , Humanos , Válvula Mitral/cirugía , Toracotomía , Resultado del TratamientoRESUMEN
BACKGROUND: Lower limb venous varicosities (VVs) are clinically common; however, their molecular underpinnings are far from well elucidated. Previous studies have demonstrated that the phenotypic transition of vascular smooth muscle cells (VSMCs) plays a critical role in VV pathogenesis and that c-fos is upregulated in VSMCs from VVs. The present study investigated the histologic and cytologic changes in VVs and the correlation between c-fos upregulation and VSMC phenotypic switching. METHODS: Thirty-four patients with VVs (VV group) and 13 patients undergoing coronary artery bypass using autologous great saphenous vein segments (normal vein [NV] group) were enrolled in the present study. The great saphenous veins of both groups were harvested for subsequent experiments. Hematoxylin and eosin staining was performed for vein morphologic analysis. Real-time quantitative polymerase chain reaction, immunohistochemistry, and Western blot assays were used to assess mRNA and protein expression of c-fos, α-smooth muscle actin (α-SMA), and osteopontin (OPN). Simple linear regression was used to evaluate the correlation between c-fos and OPN/α-SMA. Primary VSMCs were isolated from both groups and cultured in vitro. A cell counting kit-8 assay and scratch-wound assay were used to analyze the proliferation and migration abilities of the cells, respectively. RESULTS: The mean age of the patients in the NV and VV groups was 61.4 ± 3.8 years and 59.5 ± 10.4 years, respectively. The vein cavities of the VV group were dilated, and the arrangement of the cells was disordered. The tunica media of the VV group was thicker than that of the NV group owing to the accumulation and proliferation of VSMCs. Significantly elevated mRNA levels of c-fos and OPN were observed in the VV group compared with the NV group, and a positive correlation was further demonstrated between the mRNA levels of c-fos and OPN/α-SMA (R2, 0.5524; P < .001). The VSMCs derived from the VV group were more numerous (as shown by the cell counting kit-8 assay) and had a significantly greater migration speed (as shown by the scratch-wound assay) than those derived from the NV group. Moreover, the protein expression of c-fos was significantly upregulated in VSMCs derived from the VV group, and this change was accompanied by a decrease in α-SMA and an increase in OPN expression. CONCLUSIONS: Both mRNA and protein expression of c-fos were upregulated in VV specimens, and the phenotypic biomarkers (OPN/α-SMA) were altered concurrently. VSMCs derived from VVs showed increased proliferation and migration abilities. Upregulation of c-fos might play a role in the phenotypic switching of VSMCs and subsequently participate in the pathogenesis of VVs. CLINICAL RELEVANCE: C-fos is an immediate early gene owing to the transient and rapid change in its expression in response to stimuli. It is involved in the regulation of cell proliferation, cell growth, and cell movement. In the present study, varicose vein specimens showed increased mRNA and protein expression of c-fos, accompanied by altered phenotypic biomarkers. The upregulation of the c-fos gene in smooth muscle cells cultured from varicose vein specimens might be associated with phenotypic switching and functional disturbance. These results could contribute to the exploration of the molecular mechanisms underlying the pathogenesis of varicose veins and the development of new therapeutic strategies.
Asunto(s)
Extremidad Inferior/irrigación sanguínea , Músculo Liso Vascular/metabolismo , Miocitos del Músculo Liso/metabolismo , Proteínas Proto-Oncogénicas c-fos/metabolismo , Várices/metabolismo , Actinas/genética , Actinas/metabolismo , Anciano , Estudios de Casos y Controles , Movimiento Celular , Proliferación Celular , Células Cultivadas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Músculo Liso Vascular/patología , Músculo Liso Vascular/cirugía , Miocitos del Músculo Liso/patología , Osteopontina/genética , Osteopontina/metabolismo , Fenotipo , Proteínas Proto-Oncogénicas c-fos/genética , Transducción de Señal , Regulación hacia Arriba , Várices/genética , Várices/patología , Várices/cirugía , Venas/metabolismo , Venas/patología , Venas/cirugíaRESUMEN
OBJECTIVE: We aimed to study the effect of cariporide (CP) on protecting the saphenous vein and the role of acetaldehyde dehydrogenase 2 (ALDH2) in coronary artery bypass grafting (CABG). BACKGROUND: The saphenous vein is the main graft material used in CABG. Recent studies suggested that CP is effective in protecting against various cardiovascular diseases. METHODS: Segments of a surgically removed saphenous vein were used to examine the vascular response to CP. The ALDH2 genotype and expression of related proteins were assessed by Western blotting and immunohistochemistry. RESULTS: Among the conditions tested, the University of Wisconsin solution with CP (4°C, 5 min) treatment showed the best protective effect on the saphenous vein. The incidence of major adverse cardiac events was higher in the ALDH2-GA (heterozygous mutant) genotype population after CABG. CONCLUSION: CP plays a role in reducing the production of reactive oxygen species and apoptosis by ALDH2-mediated mitochondrial function improvement. The ALDH2 mutant genotype might be one of the risk factors for coronary atherosclerotic heart disease.
Asunto(s)
Aldehído Deshidrogenasa Mitocondrial/genética , Enfermedad de la Arteria Coronaria/genética , Guanidinas/uso terapéutico , Vena Safena/efectos de los fármacos , Vena Safena/patología , Sulfonas/uso terapéutico , Adenosina , Adulto , Aldehído Deshidrogenasa Mitocondrial/sangre , Alopurinol , Apoptosis/efectos de los fármacos , Puente de Arteria Coronaria/efectos adversos , Enfermedad de la Arteria Coronaria/cirugía , Femenino , Genotipo , Glutatión , Humanos , Insulina , Masculino , Persona de Mediana Edad , Soluciones Preservantes de Órganos , Rafinosa , Especies Reactivas de Oxígeno/sangre , Vena Safena/trasplanteAsunto(s)
Anemia/terapia , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Sacarato de Óxido Férrico/uso terapéutico , Complicaciones Posoperatorias/terapia , Toracotomía/efectos adversos , Administración Intravenosa , Administración Oral , Adulto , Anemia/etiología , Anemia/fisiopatología , Transfusión Sanguínea/estadística & datos numéricos , Procedimientos Quirúrgicos Cardíacos/métodos , Recuento de Eritrocitos , Eritropoyetina/uso terapéutico , Femenino , Hemoglobinas/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/fisiopatología , Estudios Retrospectivos , Toracotomía/métodos , Resultado del TratamientoRESUMEN
The asymmetric unit of the title compound, C(14)H(2)Cl(4)F(3)NO(2), contains two independent mol-ecules. In each mol-ecule, the phthalimide ring system is nearly planar [maximum atomic deviation = 0.031â (2) or 0.038â (2)â Å] and oriented with respect to the benzene ring at 65.04â (7) or 71.76â (10)°. Weak inter-molecular C-Hâ¯O and C-Hâ¯F hydrogen bonding is present in the crystal structure.