ABSTRACT
OBJECTIVE@#To explore the genetic basis for a patient with aortic root aneurysm and valve insufficiency.@*METHODS@#The patient was subjected to whole exome sequencing (WES) with a focus on the analysis of genes related to aortic aneurysm and other genetic diseases involving the cardiovascular system. Suspected pathogenic site was validated by Sanger sequencing of the patient and his family members.@*RESULTS@#WES has revealed a heterozygous c.830T>C variant (NM_001130916.3) in the patient, which was not detected among healthy members of his family. SIFT, PolyPhen2 and Mutation Taster predicted the variant to be disease causing, resulting in destruction of the structure and function of the TGFBR1 protein. Based on the American College of Medical Genetics and Genomics (ACMG) guidelines, the variant was predicted to be likely pathogenic (PM1+PM2+PM6+PP3+PP4).@*CONCLUSION@#The c.830T>C variant of the TGFBR1 gene probably underlay the disease in the proband. Above finding has enriched the spectrum of TGFBR1 gene variants in Chinese population.
Subject(s)
Humans , China , Echocardiography , Loeys-Dietz Syndrome/genetics , Mutation , Pedigree , Receptor, Transforming Growth Factor-beta Type I/genetics , Exome SequencingABSTRACT
To evaluate the relationship between atherosclerosis and hemodynamic of coronary artery in mice detecting by ultrasound bio‐microscopy flow imaging . Methods Double 14 20‐week‐old LDL‐R‐/‐and C57BL/6 male mice were selected ,and randomly divided into two groups in each genotype according to weight . Each two groups were fed to 28 weeks or 36 weeks age respectively with west diet . Coronary artery hemodynamics in these mice were assessed in vivo by Vevo ?2100 ultrasound imaging system ,then the intima‐media thickness( IM T ) of aorta in histopathology were analyzed . T he differences of coronary artery hemodynamic parameters such as maximum velocity ( Vmax ) ,mean velocity ( Vmean) and velocity time integral ( V T I) were compared between mice of different genotypes of the same week and mice of different weeks of the same genotype . And the relationship between coronary artery hemodynamic in ultrasound and aortic IM T in histopathology were analyzed . Results ① All coronary hemodynamic parameters in LDL‐R‐/‐ mice were significantly lower than those of wild‐type mice except the Vmax between two 28‐week‐old genotypes group at the same weeks of age of different genotypes ( all P ＜0 .05) . But there was no significant difference in coronary artery hemodynamic parameters between mice of the same genotype at different weeks of age( P ＞0 .05) . ②T he histopathological measurements of aortic IM T in LDL‐R‐/‐mice were significantly higher than those of wild type mice ( all P ＜ 0 .05 ) ,and those of 36‐week‐old mice were significantly higher than those of 28‐week‐old mice ( all P ＜ 0 .05 ) . ③ All coronary hemodynamic parameters such as Vmax ,Vmean and V TI were negatively correlated with pathological measurements of aortic IM T ( r ＝ －0 .532 , －0 .423 , －0 .524 ; all P ＜ 0 .05 ) . Conclusions The parameters of coronary artery hemodynamics obtained by ultrasound bio‐microscopy are well correlated with the pathological results of atherosclerosis . Ultrasound bio‐microscopic flow imaging can be used as a new method to evaluate the degree of atherosclerosis in mice by detecting the hemodynamic parameters of coronary artery .
ABSTRACT
Objective To evaluate the different change in atherosclerosis between apolipoprotein E knockout ( ApoE-/-) mice and low density lipoprotein receptor knockout ( LDL-R-/-) mice in different diet by vivo ultrasound biomicroscopy(UBM) . Methods Thirty-two 8 weeks age ApoE-/- mice and twenty-eight 20 weeks age LDL-R-/- mice were selected ,and each mouse model were divided into four groups randomly according to weight . Two groups of each model were fed with normal diet for 8 weeks and 16 weeks respectively as general groups ,and two other groups were fed with west diet as high-fat groups . Intima-media thickness ( IM T ) in the aortic root of all groups were assessed by Vevo 770 UBM , and all measurementsofUBMwerecomparedwithhistopathologyandblood-fat.Results ①Thickenwallor plaque in aortic root showed by UBM and histopathology could be found in ApoE-/- mice in all diet conditions ,but the changes in LDL-R-/- mice only could be found in high-fat diet conditions;② IM T of ApoE-/- mice measured in histopathology were significantly higher than LDL-R-/- mice in all diet condition ( P<0 .05) ,but in UBM ,the IMT of ApoE-/- mice showed significantly higher than that of LDL-R-/- mice only in general diet groups and 8 weeks high-fat diet group ( P <0 .05) ;③In blood-fat ,the total cholesterol ( TC) in ApoE-/- mice were significantly higher than that of LDL-R-/- mice in all diet conditions ( P <0 .05) . But triglyceride ( TG) was higher only in general diet when it was compared between ApoE-/- mice and LDL-R-/- mice . Conclusions It is recommend to select ApoE-/- mice as animal model in atherosclerosis study rather than LDL-R-/- mice ,because the higher serum TC and higher susceptible of atherosclerosis in ApoE-/- mice . The west diet is necessary if LDL-R-/- mice was used to atherosclerosis study .
ABSTRACT
Objective To evaluate the value of ultrasound biomicroscopy (UBM) in assessment of atherosclerosis in apolipoprotein E (ApoE) knockout mice feeding with western diet.Methods Sixteen ApoE knockout mice in 8 weeks age were selected,then divided into two groups.One group was fed with west diet as high-fat group,and another group was fed with normal diet as control group.Intima-media thickness (IMT) and plaque area in the aortic root were assessed by UBM in two groups after 8 weeks and 16 weeks.And the measurements of UBM were compared with results of histopathology and blood-fat.ResultsThicken wall and plaque could be find in aortic root in control group and high-fat diet group byUBM.IMT and plaque area in high-fat diet group was significantly higher than those of control group ( P ＜ 0.05).The IMT and plaque area in UBM were good correlation with histopathology ( rwas 0.81 and 0.70 respectively).The triglyceride(TC) and total cholesterol in high-fat diet group was significantly higher than those of control group ( P ＜0.05),and IMT in UBM were increased with the elevated level of TC,there was a positive correlation between IMT and TC( r =0.528).ConclusionsWestern diet can accelerate the process in formation of atherosclerotic plaque in ApoE knockout mice.UBM can be used to observe this prograss noninvasively in vivo mice.
ABSTRACT
Objective To establish the method and cardiovascular imaging in mice using ultrasound biomicroscopy(UBM) with anatomical confirmation by magnetic resonance (MR) imaging, and to evaluate the feasibility and value of UBM in mice cardiovascular imaging.Methods The mouse thoracic anatomy was elucidated using Signo 3.0T MR imaging on 2 healthy C57BL/6 adult male mice.The structures and flow of mice heart and great vessels in 16 healthy C57BL/6 adult male mice were showed and analyzed by Visualsonics Vevo 770 UBM through several acoustic windows, including left parasternal, right parasternal, apical regions, and suprasternalis.The systolic and diastolic function of mice heart were also evaluated.ResultsAnatomic characteristic of mice could be displayed by MR imaging.The heart was mostly located in left thoracic cavity.The angle between long axis of the heart and the midline of the chest was about 45 degrees.Left atrium,left ventricle, mitral valve and right ventricle were located on the left side of the midline of the chest.Aortic valve orifice, ascending aorta,right atrium and tricuspid valve were located on the right side of the midline of the chest.Left heart long axis view,left ventricular short axis view,ascending aorta long axis view,long axis view of aortic arch, aortic short axis view, right ventricular inflow tract long axis view, pulmonary artery long axis view and so on were obtained clearly using UBM.The structures of heart and great vessels were displayed and the cardiovascular parameters could be measured accurately,including left atrium,left ventricle,aorta and aortic arch,interventricular septum,right atrium, right ventricle, pulmonary artery, innominate artery, right internal carotid artery and the velocity in each valve orifices from Doppler flow spectrum.No significant difference was found in the measurements between different age groups.Conclusions The cardiovascular structures and hemodynamics could be displayed by UBM in mice when appropriate acoustic windows and sections were selected.This novel imaging protocol provides us a non-invasive way to follow atherosclerosis in genes knockout mice.
ABSTRACT
ApoE and LDL-R knocking out mouse may spontaneously develope atherosclerosis and so is applied in the research of atherosclerosis. These mouse model, the model generated by gene targeting, like IL-1, C-reactive protein, scavenger receptor, IgG Fc,C1q and CD44, play important role in research of inflammatory factor and immune factor on atherosclerosis.