Hypertrophic cardiomyopathy(HCM)is one of the most common inherited cardiovascular diseases,with a global prevalence estimated at 0.2%to 0.5%.1 It is characterized by left ventricular hypertrophy which could not be ex...Hypertrophic cardiomyopathy(HCM)is one of the most common inherited cardiovascular diseases,with a global prevalence estimated at 0.2%to 0.5%.1 It is characterized by left ventricular hypertrophy which could not be explained by abnormal loading conditions,and a considerable proportion of patients were accompanied by either resting or inducible left ventricular outflow tract(LVOT)obstruction,leading to impaired cardiac function,mitral regurgitation due to systolic anterior motion(SAM)condition,with subsequent reduced quality of life,adverse clinical outcomes or even sudden death(Supplementary Text 1 online).2 HCM was previously believed to exhibit an autosomal dominant inheritance pattern,typically caused by pathogenic mutations in genes encoding sarcomeric proteins,with MYBPC3 and MYH7 being the most commonly involved genes.3 However,about 60%of all patients test negative for sarcomeric variants,4 suggesting a possible polygenic inheritance pattern in these patients and the contribution of non-genetic factors on disease phenotype(Supplementary Text 2 online).展开更多
In situ regeneration of tissue-engineered heart valves(TEHV)is a promising strategy to overcome the limitations of existing heart valve prostheses.Although,decellularized aortic valves(DAVs)are widely regarded as a sc...In situ regeneration of tissue-engineered heart valves(TEHV)is a promising strategy to overcome the limitations of existing heart valve prostheses.Although,decellularized aortic valves(DAVs)are widely regarded as a scaffold in the construction of TEHV,the poor hemocompatibility and adverse immune responses make DAV scaffolds prone to thrombosis and degradation,thus hindering recellularization and in situ regeneration.Our study developed an immune-regulatory strategy involving the use of hydrogel-encapsulated nanoparticles to modify DAV scaffolds.Specifically,folic acid-and hyaluronic acid-modified mesoporous silica nanoparticles(FA-HAMSNs@CY-09)were engineered to deliver NOD-like receptor family,pyrin domain containing 3(NLRP3)in-hibitor CY-09,thereby targeting macrophages,modulating their polarization and establishing a pro-regenerative immune microenvironment.The reactive oxygen species(ROS)-responsive hydrogel delivering FA-HAMSNs@CY-09 enabled intelligent nanoparticle release and ROS scavenging.Results demonstrated that the hydrogel-modified DAV scaffold exhibited ROS-responsive release of FA-HA-MSNs@CY-09,which effectively induced macrophage polarization toward the pro-remodeling M2 phenotype.In vitro,the scaffold showed favorable mechanical properties,cytocompatibility,and hemocompatibility.Transcriptome sequencing eluci-dated the macrophage-reprogramming mechanism of the scaffold.In vivo,the scaffolds promoted significant M2 macrophage infiltration shortly after implantation,facilitating endothelial tissue formation.This resulted in enhanced endothelialization and interstitial cell infiltration under blood flow,without thrombosis or calcifica-tion.The novel heart valve overcomes various limitations of conventional heart valve prostheses and demon-strates considerable promise for clinical translation,particularly as an immunomodulatory biomaterial strategy.展开更多
Mitral valve regurgitation(MR)is a common heart valve disease that affects>10%of the elderly population.Epidemiological data estimate that the number of MR patients has reached more than2.5 million in the USA,with ...Mitral valve regurgitation(MR)is a common heart valve disease that affects>10%of the elderly population.Epidemiological data estimate that the number of MR patients has reached more than2.5 million in the USA,with an extremely low surgical intervention rate(<5%)[1].展开更多
Transcatheter edge-to-edge repair(TEER)of the mitral valve has emerged as a standard treatment for patients with severe degenerative mitral regurgitation at high or prohibitive surgical risk.The devices approved by th...Transcatheter edge-to-edge repair(TEER)of the mitral valve has emerged as a standard treatment for patients with severe degenerative mitral regurgitation at high or prohibitive surgical risk.The devices approved by the Food and Drug Administration including MitraClip(Abbott Vascular,California,USA)and PASCAL(Edwards Lifesciences,California,USA)cost over$33,000 in western countries.[1]This pricing presents a significant economic burden especially in developing countries,where TEER devices are typically not covered by health insurance.展开更多
The surgical treatment of isolated tricuspid regurgitation presents a notable mortality risk,particularly in patients who are referred late.Tricuspid transcatheter edge-to-edge repair(TEER)has become a safe and effect...The surgical treatment of isolated tricuspid regurgitation presents a notable mortality risk,particularly in patients who are referred late.Tricuspid transcatheter edge-to-edge repair(TEER)has become a safe and effective therapeutic option for patients with tricuspid regurgitation.^([1])The Kyrin^(TM)Tricuspid TEER system(Shenqi Medical,Shanghai,China)consists of a 24-French delivery catheter that is used to place one or more clips devices on the tricuspid-valve leaflets.Four clip sizes are available with a 12-or 9-mm arm length and 6-or 4-mm arm width.Herein,we report the initial result of using this tricuspid TEER system in Chinese patients with severe tricuspid regurgitation.展开更多
基金supported by the National Natural Science Foundation of China(82460073)the National Key Research and Development Program(2022YFC2503400)+1 种基金the Major Science and Technology Special Plan Project of Yunnan Province(202302AA310045)the Talent Trusteeship Program of Fuwai Yunnan Hospital(2024RCTJ-QN008).
文摘Hypertrophic cardiomyopathy(HCM)is one of the most common inherited cardiovascular diseases,with a global prevalence estimated at 0.2%to 0.5%.1 It is characterized by left ventricular hypertrophy which could not be explained by abnormal loading conditions,and a considerable proportion of patients were accompanied by either resting or inducible left ventricular outflow tract(LVOT)obstruction,leading to impaired cardiac function,mitral regurgitation due to systolic anterior motion(SAM)condition,with subsequent reduced quality of life,adverse clinical outcomes or even sudden death(Supplementary Text 1 online).2 HCM was previously believed to exhibit an autosomal dominant inheritance pattern,typically caused by pathogenic mutations in genes encoding sarcomeric proteins,with MYBPC3 and MYH7 being the most commonly involved genes.3 However,about 60%of all patients test negative for sarcomeric variants,4 suggesting a possible polygenic inheritance pattern in these patients and the contribution of non-genetic factors on disease phenotype(Supplementary Text 2 online).
基金supported by the National Key Project of Research and Development Plan during the 14th Five-Year Plan Period(Grant No.2022YFC2503400)the National Natural Science Foundation of China(Grant No.82322007,82460073)+2 种基金Major science and technology special plan project of Yunnan Province(Grant No.202302AA310045)the Research Grant of Key Laboratory of Molecular Biological Targeted Therapies of the Ministry of Education(Huazhong University of Science and Technology)[No.2024SWBS014]the Open Foundation of Hubei Key Laboratory of Regenerative Medicine and Multi-disciplinary Translational Research[No.2024zsyx12].
文摘In situ regeneration of tissue-engineered heart valves(TEHV)is a promising strategy to overcome the limitations of existing heart valve prostheses.Although,decellularized aortic valves(DAVs)are widely regarded as a scaffold in the construction of TEHV,the poor hemocompatibility and adverse immune responses make DAV scaffolds prone to thrombosis and degradation,thus hindering recellularization and in situ regeneration.Our study developed an immune-regulatory strategy involving the use of hydrogel-encapsulated nanoparticles to modify DAV scaffolds.Specifically,folic acid-and hyaluronic acid-modified mesoporous silica nanoparticles(FA-HAMSNs@CY-09)were engineered to deliver NOD-like receptor family,pyrin domain containing 3(NLRP3)in-hibitor CY-09,thereby targeting macrophages,modulating their polarization and establishing a pro-regenerative immune microenvironment.The reactive oxygen species(ROS)-responsive hydrogel delivering FA-HAMSNs@CY-09 enabled intelligent nanoparticle release and ROS scavenging.Results demonstrated that the hydrogel-modified DAV scaffold exhibited ROS-responsive release of FA-HA-MSNs@CY-09,which effectively induced macrophage polarization toward the pro-remodeling M2 phenotype.In vitro,the scaffold showed favorable mechanical properties,cytocompatibility,and hemocompatibility.Transcriptome sequencing eluci-dated the macrophage-reprogramming mechanism of the scaffold.In vivo,the scaffolds promoted significant M2 macrophage infiltration shortly after implantation,facilitating endothelial tissue formation.This resulted in enhanced endothelialization and interstitial cell infiltration under blood flow,without thrombosis or calcifica-tion.The novel heart valve overcomes various limitations of conventional heart valve prostheses and demon-strates considerable promise for clinical translation,particularly as an immunomodulatory biomaterial strategy.
基金supported by a grant from Yunnan Provincial Cardiovascular Disease Clinical Medical Center Project(FZX201906-01)。
文摘Mitral valve regurgitation(MR)is a common heart valve disease that affects>10%of the elderly population.Epidemiological data estimate that the number of MR patients has reached more than2.5 million in the USA,with an extremely low surgical intervention rate(<5%)[1].
基金supported by the National Key R&D Program of China(2022YFC2503400)Major science and technology special plan project of Yunnan Province(202302AA310045)Yunnan Provincial Clinical Research Center for Cardiovascular Diseases(202102AA310002).
文摘Transcatheter edge-to-edge repair(TEER)of the mitral valve has emerged as a standard treatment for patients with severe degenerative mitral regurgitation at high or prohibitive surgical risk.The devices approved by the Food and Drug Administration including MitraClip(Abbott Vascular,California,USA)and PASCAL(Edwards Lifesciences,California,USA)cost over$33,000 in western countries.[1]This pricing presents a significant economic burden especially in developing countries,where TEER devices are typically not covered by health insurance.
基金supported by the National Key R&D Program of China(2022YFC2503400)the Major Science and Technology Special Plan Project of Yunnan Province(202302AA310045).
文摘The surgical treatment of isolated tricuspid regurgitation presents a notable mortality risk,particularly in patients who are referred late.Tricuspid transcatheter edge-to-edge repair(TEER)has become a safe and effective therapeutic option for patients with tricuspid regurgitation.^([1])The Kyrin^(TM)Tricuspid TEER system(Shenqi Medical,Shanghai,China)consists of a 24-French delivery catheter that is used to place one or more clips devices on the tricuspid-valve leaflets.Four clip sizes are available with a 12-or 9-mm arm length and 6-or 4-mm arm width.Herein,we report the initial result of using this tricuspid TEER system in Chinese patients with severe tricuspid regurgitation.
