Background:Calcific aortic valve stenosis(CAVS)is one of the most challenging heart diseases in clinical with rapidly increasing prevalence.However,study of the mecha-nism and treatment of CAVS is hampered by the lack...Background:Calcific aortic valve stenosis(CAVS)is one of the most challenging heart diseases in clinical with rapidly increasing prevalence.However,study of the mecha-nism and treatment of CAVS is hampered by the lack of suitable,robust and efficient models that develop hemodynamically significant stenosis and typical calcium deposi-tion.Here,we aim to establish a mouse model to mimic the development and features of CAVS.Methods:The model was established via aortic valve wire injury(AVWI)combined with vitamin D subcutaneous injected in wild type C57/BL6 mice.Serial transthoracic echocardiography was applied to evaluate aortic jet peak velocity and mean gradi-ent.Histopathological specimens were collected and examined in respect of valve thickening,calcium deposition,collagen accumulation,osteogenic differentiation and inflammation.Results:Serial transthoracic echocardiography revealed that aortic jet peak velocity and mean gradient increased from 7 days post model establishment in a time depend-ent manner and tended to be stable at 28 days.Compared with the sham group,sim-ple AVWI or the vitamin D group,the hybrid model group showed typical pathological features of CAVS,including hemodynamic alterations,increased aortic valve thicken-ing,calcium deposition,collagen accumulation at 28 days.In addition,osteogenic dif-ferentiation,fibrosis and inflammation,which play critical roles in the development of CAVS,were observed in the hybrid model.Conclusions:We established a novel mouse model of CAVS that could be induced efficiently,robustly and economically,and without genetic intervention.It provides a fast track to explore the underlying mechanisms of CAVS and to identify more effec-tive pharmacological targets.展开更多
Considering the surgical risk stratification for patients with severe calcific aortic stenosis(AS),transcatheter aortic valve replacement(TAVR)is a reliable alternative to surgical aortic valve replacement(SAVR)(Fan e...Considering the surgical risk stratification for patients with severe calcific aortic stenosis(AS),transcatheter aortic valve replacement(TAVR)is a reliable alternative to surgical aortic valve replacement(SAVR)(Fan et al.,2020,2021;Lee et al.,2021).Despite the favorable clinical benefits of TAVR,stroke remains a dreaded perioperative complication(Auffret et al.,2016;Kapadia et al.,2016;Kleiman et al.,2016;Huded et al.,2019).Ischemic overt stroke,identified in 1.4%to 4.3%of patients in TAVR clinical practice,has been associated with prolonged disability and increased mortality(Auffret et al.,2016;Kapadia et al.,2016;Levi et al.,2022).The prevalence of hyperintensity cerebral ischemic lesions detected by diffusion-weighted magnetic resonance imaging(DW-MRI)was reported to be about 80%,which is associated with impaired neurocognitive function and vascular dementia(Vermeer et al.,2003;Barber et al.,2008;Kahlert et al.,2010).展开更多
Transcatheter aortic valve replacement(TAVR)has emerged as a viable treatment option for patients with severe aortic stenosis regardless of its surgical risk stratification(Otto et al.,2021).Aortic angulation is usual...Transcatheter aortic valve replacement(TAVR)has emerged as a viable treatment option for patients with severe aortic stenosis regardless of its surgical risk stratification(Otto et al.,2021).Aortic angulation is usually measured as the angle between the horizon-tai and the aortic annulus planes based on preprocedural multidetector computed tomography(MDCT)(Al-Lamee et al.,2011).Extremely horizontal aorta,defined as an aortic angulation greater than 70°.展开更多
基金National Natural Science Foundation of China,Grant/Award Number:81770252,82030014,82271606 and U22A20267Binjiang Institute of Zhejiang University,Grant/Award Number:ZY202205SMKY001Key Program of Major Science and Technology Projects in Zhejiang Province,Grant/Award Number:2021C03097 and 2022C03063。
文摘Background:Calcific aortic valve stenosis(CAVS)is one of the most challenging heart diseases in clinical with rapidly increasing prevalence.However,study of the mecha-nism and treatment of CAVS is hampered by the lack of suitable,robust and efficient models that develop hemodynamically significant stenosis and typical calcium deposi-tion.Here,we aim to establish a mouse model to mimic the development and features of CAVS.Methods:The model was established via aortic valve wire injury(AVWI)combined with vitamin D subcutaneous injected in wild type C57/BL6 mice.Serial transthoracic echocardiography was applied to evaluate aortic jet peak velocity and mean gradi-ent.Histopathological specimens were collected and examined in respect of valve thickening,calcium deposition,collagen accumulation,osteogenic differentiation and inflammation.Results:Serial transthoracic echocardiography revealed that aortic jet peak velocity and mean gradient increased from 7 days post model establishment in a time depend-ent manner and tended to be stable at 28 days.Compared with the sham group,sim-ple AVWI or the vitamin D group,the hybrid model group showed typical pathological features of CAVS,including hemodynamic alterations,increased aortic valve thicken-ing,calcium deposition,collagen accumulation at 28 days.In addition,osteogenic dif-ferentiation,fibrosis and inflammation,which play critical roles in the development of CAVS,were observed in the hybrid model.Conclusions:We established a novel mouse model of CAVS that could be induced efficiently,robustly and economically,and without genetic intervention.It provides a fast track to explore the underlying mechanisms of CAVS and to identify more effec-tive pharmacological targets.
基金supported by the National Key R&D Program of China(2020YFC2008100)the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2017-12M-3002)+2 种基金the Zhejiang Province Science and Technology Department Key R&D Program(2021C03097 and 2022C03063)the Binjiang Institute of Zhejiang University(ZY202205SMKY001)the Natural Science Foundation of Zhejiang Province(LQ22H020008)。
基金supported by the Zhejiang Province Science and Technology Department Key R&D Program(No.2021C03097),China.
文摘Considering the surgical risk stratification for patients with severe calcific aortic stenosis(AS),transcatheter aortic valve replacement(TAVR)is a reliable alternative to surgical aortic valve replacement(SAVR)(Fan et al.,2020,2021;Lee et al.,2021).Despite the favorable clinical benefits of TAVR,stroke remains a dreaded perioperative complication(Auffret et al.,2016;Kapadia et al.,2016;Kleiman et al.,2016;Huded et al.,2019).Ischemic overt stroke,identified in 1.4%to 4.3%of patients in TAVR clinical practice,has been associated with prolonged disability and increased mortality(Auffret et al.,2016;Kapadia et al.,2016;Levi et al.,2022).The prevalence of hyperintensity cerebral ischemic lesions detected by diffusion-weighted magnetic resonance imaging(DW-MRI)was reported to be about 80%,which is associated with impaired neurocognitive function and vascular dementia(Vermeer et al.,2003;Barber et al.,2008;Kahlert et al.,2010).
基金This work was supported by the Zhejiang Province Science and Technology Department Key R&D Program(Nos.2021C03097 and 2018C03084),China.
文摘Transcatheter aortic valve replacement(TAVR)has emerged as a viable treatment option for patients with severe aortic stenosis regardless of its surgical risk stratification(Otto et al.,2021).Aortic angulation is usually measured as the angle between the horizon-tai and the aortic annulus planes based on preprocedural multidetector computed tomography(MDCT)(Al-Lamee et al.,2011).Extremely horizontal aorta,defined as an aortic angulation greater than 70°.
