Background The cardiac extracellular matrix(ECM)undergoes ongoing modification following myocardial infarction(MI),driving the inflammation and repair response.Collagens,the major component of ECM,regulate the healing...Background The cardiac extracellular matrix(ECM)undergoes ongoing modification following myocardial infarction(MI),driving the inflammation and repair response.Collagens,the major component of ECM,regulate the healing process uniquely after MI,where they are synthesized and accumulated to form scars in the infarcted area.Various types of collagens affect the repair response in different ways.Knowing the exact processes of collagen regulation can facilitate the development of new therapeutic options for associated disorders.In this review,we summarize the roles of various collagen types in heart repair after injury.展开更多
The loss of cardiomyocytes during injury and disease can result in heart failure and sudden death, while the adult heart has a limited capacity for endogenous regeneration and repair. Current stem cell-based regenerat...The loss of cardiomyocytes during injury and disease can result in heart failure and sudden death, while the adult heart has a limited capacity for endogenous regeneration and repair. Current stem cell-based regenerative medicine approaches modestly improve cardiomyocyte survival, but offer neglectable cardiomyogenesis. This has prompted the need for methodological developments that crease de novo cardiomyocytes. Current insights in cardiac development on the processes and regulatory mechanisms in embryonic cardiomyocyte differentiation provide a basis to therapeutically induce these pathways to generate new cardiomyocytes. Here, we discuss the current knowledge on embryonic cardiomyocyte differentiation and the implementation of this knowledge in state-ofthe-art protocols to the direct reprogramming of cardiac fibroblasts into de novo cardiomyocytes in vitro and in vivo with an emphasis on micro RNA-mediated reprogramming. Additionally, we discuss current advances on state-of-theart targeted drug delivery systems that can be employed to deliver these micro RNAs to the damaged cardiac tissue. Together, the advances in our understanding of cardiac development, recent advances in micro RNAbased therapeutics, and innovative drug delivery systems, highlight exciting opportunities for effective therapies for myocardial infarction and heart failure.展开更多
Over the last years, stem cell therapy has emerged asan inspiring alternative to restore cardiac function after myocardial infarction. A large body of evidence has been obtained in this field but there is no conclusiv...Over the last years, stem cell therapy has emerged asan inspiring alternative to restore cardiac function after myocardial infarction. A large body of evidence has been obtained in this field but there is no conclusive data on the efficacy of these treatments. Preclinical studies and early reports in humans have been encouraging and have fostered a rapid clinical translation, but positive results have not been uniformly observed and when present, they have been modest. Several types of stem cells, manufacturing methods and delivery routes have been tested in different clinical settings but direct comparison between them is challenging and hinders further research. Despite enormous achievements, major barriers have been found and many fundamental issues remain to be resolved. A better knowledge of the molecular mechanisms implicated in cardiac development and myocardial regeneration is critically needed to overcome some of these hurdles. Genetic and pharmacological priming together with the discovery of new sources of cells have led to a "second generation" of cell products that holds an encouraging promise in cardiovascular regenerative medicine. In this report, we review recent advances in this field focusing on the new types of stem cells that are currently being tested in human beings and on the novel strategies employed to boost cell performance in order to improve cardiac function and outcomes after myocardial infarction.展开更多
Inflammation and ischemic microenvironments represent significant challenges in cardiac repair.To address these issues,we developed a series of dual-dynamically crosslinked alginate-based hydrogels(SA-PBA/E/Sr)contain...Inflammation and ischemic microenvironments represent significant challenges in cardiac repair.To address these issues,we developed a series of dual-dynamically crosslinked alginate-based hydrogels(SA-PBA/E/Sr)containing strontium ions(Sr^(2+))and epigallocatechin gallate(EGCG),which demonstrate microenvironment modulation and angiogenic capabilities in the myocardial infarction(MI)microenvironment.In the SA-PBA/E/Sr hydrogel system,alginate modified with aminophenylboronic acid(PBA)was synthesized to form boronic acid ester bonds with EGCG and an ionic coordination network with Sr^(2+)ions.The resulting hydrogel exhibits excellent injectability due to its dual-dynamically crosslinked structure,with its formation and mechanical properties being tunable modulated by the PBA substitution degree,EGCG concentration,and Sr^(2+)content.The incorporation of EGCG enables the hydrogel to efficiently scavenge reactive oxygen species(ROS)and mitigate oxidative stress-induced cellular damage under hypoxia.Furthermore,the introduction of Sr^(2+)significantly enhances the migratory capacity of endothelial cells,a critical factor in angiogenesis.In vivo experiments revealed that the injection of SA-PBA/E/Sr hydrogel into the infarcted myocardium of Sprague-Dawley(SD)rats led to reduced ROS levels,alleviated inflammatory responses,suppression of pro-inflammatory M1 macrophage expression,enhancement of anti-inflammatory M2 macrophage expression,and accelerated neovascularization in the damaged tissue.Echocardiographic and histological analyses demonstrated a remarkable increase in ejection fraction and a decreased infarct size,collectively indicating significant cardiac functional recovery.展开更多
Cardiac stromal cells have faced through the years a significant evolution in their definitions concerning their phenotypes,markers,and functions.They are surging to key roles in physiopathology,becoming important tar...Cardiac stromal cells have faced through the years a significant evolution in their definitions concerning their phenotypes,markers,and functions.They are surging to key roles in physiopathology,becoming important targets to be exploited for cardiac repair.In this perspective,we briefly discuss their role in novel therapeutic strategies for enhancing cardiac repair and regeneration.展开更多
A left ventricular (LV) free wall rupture is a highly lethal condition. A 75-year-old female who experienced chest pain was diagnosed as having an acute aortic dissection Stanford type A and underwent emergent surgery...A left ventricular (LV) free wall rupture is a highly lethal condition. A 75-year-old female who experienced chest pain was diagnosed as having an acute aortic dissection Stanford type A and underwent emergent surgery. Under cardiopulmonary bypass with LV venting through the right superior pulmonary vein, a proximal aortic stamp was formed. The patient was cooled, selective antegrade brain perfusion was performed, and a hemiarch repair was performed. After the patient was transferred to the intensive care unit, her blood pressure suddenly fell to 50 mmHg. She had a blowout rupture in the left ventricular anterolateral free wall. Since the bleeding hall was not large and the damage to the surrounding left ventricular tissue was not very wide, an off-pump multilayered sutureless repair was performed by using three layers of collagen fleece squares with fibrinogen-based impregnation (TachoComb;CSL Behring, Tokyo, Japan) and three layers of gelatin-resorcin-formalin glue reinforced by an equine pericardial patch (Xenomedica;Edwards Lifesciences, LLC, Irvine, CA). The blow-out rupture seemed to be caused by perioperative myocardial infarction generated by the compression of the left ventricular vent to the LV lateral wall. The patient was free from re-rupture or aneurysm enlargement. The thickness of the hemostatic material seemed to help control the bulging of the aneurysm and to prevent further LV aneurysm enlargement and re-rupture.展开更多
A 74-year-old man was admitted to the cardiac catheterization laboratory with acute myocardial infarction. After successful angioplasty and stent implantation into the right coronary artery, he developed cardiogenic s...A 74-year-old man was admitted to the cardiac catheterization laboratory with acute myocardial infarction. After successful angioplasty and stent implantation into the right coronary artery, he developed cardiogenic shock the following day. Echocardiography showed ventricular septal rupture. Cardiac magnet resonance imaging (MRI) was performed on the critically ill patient and provided detailed information on size and localization of the ruptured septum by the use of fast MRI sequences. Moreover, the MRI revealed that the ventricular septal rupture was within the myocardial infarction area, which was substantially larger than the rupture. As the patient's condition worsened, he was intubated and had intra-aortic balloon pump implanted, and extracorporeal membrane oxygenation was initiated. During the following days, the patient's situation improved, and surgical correction of the ventricular septal defect could successfully be performed. To the best of our knowledge, this case report is the first description of postinfarction ventricular septal rupture by the use of cardiac MRI in an intensive care patient with cardiogenic shock and subsequent successful surgical repair.展开更多
基金sponsored by grants from the National key R&D Program of China(No.2018YFA0108100)National Natural Science Foundation of China(No.32200592,No.92268103)+2 种基金the Chinese Postdoctoral Science Foundation(No.2021TQ0328,No.2022M710144)Shanghai Rising-Star Program(No.20QA1406900)the Shanghai Tech University start-up fund
文摘Background The cardiac extracellular matrix(ECM)undergoes ongoing modification following myocardial infarction(MI),driving the inflammation and repair response.Collagens,the major component of ECM,regulate the healing process uniquely after MI,where they are synthesized and accumulated to form scars in the infarcted area.Various types of collagens affect the repair response in different ways.Knowing the exact processes of collagen regulation can facilitate the development of new therapeutic options for associated disorders.In this review,we summarize the roles of various collagen types in heart repair after injury.
文摘The loss of cardiomyocytes during injury and disease can result in heart failure and sudden death, while the adult heart has a limited capacity for endogenous regeneration and repair. Current stem cell-based regenerative medicine approaches modestly improve cardiomyocyte survival, but offer neglectable cardiomyogenesis. This has prompted the need for methodological developments that crease de novo cardiomyocytes. Current insights in cardiac development on the processes and regulatory mechanisms in embryonic cardiomyocyte differentiation provide a basis to therapeutically induce these pathways to generate new cardiomyocytes. Here, we discuss the current knowledge on embryonic cardiomyocyte differentiation and the implementation of this knowledge in state-ofthe-art protocols to the direct reprogramming of cardiac fibroblasts into de novo cardiomyocytes in vitro and in vivo with an emphasis on micro RNA-mediated reprogramming. Additionally, we discuss current advances on state-of-theart targeted drug delivery systems that can be employed to deliver these micro RNAs to the damaged cardiac tissue. Together, the advances in our understanding of cardiac development, recent advances in micro RNAbased therapeutics, and innovative drug delivery systems, highlight exciting opportunities for effective therapies for myocardial infarction and heart failure.
文摘Over the last years, stem cell therapy has emerged asan inspiring alternative to restore cardiac function after myocardial infarction. A large body of evidence has been obtained in this field but there is no conclusive data on the efficacy of these treatments. Preclinical studies and early reports in humans have been encouraging and have fostered a rapid clinical translation, but positive results have not been uniformly observed and when present, they have been modest. Several types of stem cells, manufacturing methods and delivery routes have been tested in different clinical settings but direct comparison between them is challenging and hinders further research. Despite enormous achievements, major barriers have been found and many fundamental issues remain to be resolved. A better knowledge of the molecular mechanisms implicated in cardiac development and myocardial regeneration is critically needed to overcome some of these hurdles. Genetic and pharmacological priming together with the discovery of new sources of cells have led to a "second generation" of cell products that holds an encouraging promise in cardiovascular regenerative medicine. In this report, we review recent advances in this field focusing on the new types of stem cells that are currently being tested in human beings and on the novel strategies employed to boost cell performance in order to improve cardiac function and outcomes after myocardial infarction.
基金supported by the National Natural Science Foundation of China(32471384).
文摘Inflammation and ischemic microenvironments represent significant challenges in cardiac repair.To address these issues,we developed a series of dual-dynamically crosslinked alginate-based hydrogels(SA-PBA/E/Sr)containing strontium ions(Sr^(2+))and epigallocatechin gallate(EGCG),which demonstrate microenvironment modulation and angiogenic capabilities in the myocardial infarction(MI)microenvironment.In the SA-PBA/E/Sr hydrogel system,alginate modified with aminophenylboronic acid(PBA)was synthesized to form boronic acid ester bonds with EGCG and an ionic coordination network with Sr^(2+)ions.The resulting hydrogel exhibits excellent injectability due to its dual-dynamically crosslinked structure,with its formation and mechanical properties being tunable modulated by the PBA substitution degree,EGCG concentration,and Sr^(2+)content.The incorporation of EGCG enables the hydrogel to efficiently scavenge reactive oxygen species(ROS)and mitigate oxidative stress-induced cellular damage under hypoxia.Furthermore,the introduction of Sr^(2+)significantly enhances the migratory capacity of endothelial cells,a critical factor in angiogenesis.In vivo experiments revealed that the injection of SA-PBA/E/Sr hydrogel into the infarcted myocardium of Sprague-Dawley(SD)rats led to reduced ROS levels,alleviated inflammatory responses,suppression of pro-inflammatory M1 macrophage expression,enhancement of anti-inflammatory M2 macrophage expression,and accelerated neovascularization in the damaged tissue.Echocardiographic and histological analyses demonstrated a remarkable increase in ejection fraction and a decreased infarct size,collectively indicating significant cardiac functional recovery.
基金IC is supported by Grant#RG11916B85CDBF76 from Sapienza UniversityVP is supported by Grant#AR120172B8B543B3 from Sapienza University.FP is supported by Grant#A0375-2020-36621 from Regione Lazio(POR-FESR 2014-2021).
文摘Cardiac stromal cells have faced through the years a significant evolution in their definitions concerning their phenotypes,markers,and functions.They are surging to key roles in physiopathology,becoming important targets to be exploited for cardiac repair.In this perspective,we briefly discuss their role in novel therapeutic strategies for enhancing cardiac repair and regeneration.
文摘A left ventricular (LV) free wall rupture is a highly lethal condition. A 75-year-old female who experienced chest pain was diagnosed as having an acute aortic dissection Stanford type A and underwent emergent surgery. Under cardiopulmonary bypass with LV venting through the right superior pulmonary vein, a proximal aortic stamp was formed. The patient was cooled, selective antegrade brain perfusion was performed, and a hemiarch repair was performed. After the patient was transferred to the intensive care unit, her blood pressure suddenly fell to 50 mmHg. She had a blowout rupture in the left ventricular anterolateral free wall. Since the bleeding hall was not large and the damage to the surrounding left ventricular tissue was not very wide, an off-pump multilayered sutureless repair was performed by using three layers of collagen fleece squares with fibrinogen-based impregnation (TachoComb;CSL Behring, Tokyo, Japan) and three layers of gelatin-resorcin-formalin glue reinforced by an equine pericardial patch (Xenomedica;Edwards Lifesciences, LLC, Irvine, CA). The blow-out rupture seemed to be caused by perioperative myocardial infarction generated by the compression of the left ventricular vent to the LV lateral wall. The patient was free from re-rupture or aneurysm enlargement. The thickness of the hemostatic material seemed to help control the bulging of the aneurysm and to prevent further LV aneurysm enlargement and re-rupture.
基金Supported by The German Research Foundation (DFG) and the University of Wuerzburg through the Open Access Publishing Funding Programme
文摘A 74-year-old man was admitted to the cardiac catheterization laboratory with acute myocardial infarction. After successful angioplasty and stent implantation into the right coronary artery, he developed cardiogenic shock the following day. Echocardiography showed ventricular septal rupture. Cardiac magnet resonance imaging (MRI) was performed on the critically ill patient and provided detailed information on size and localization of the ruptured septum by the use of fast MRI sequences. Moreover, the MRI revealed that the ventricular septal rupture was within the myocardial infarction area, which was substantially larger than the rupture. As the patient's condition worsened, he was intubated and had intra-aortic balloon pump implanted, and extracorporeal membrane oxygenation was initiated. During the following days, the patient's situation improved, and surgical correction of the ventricular septal defect could successfully be performed. To the best of our knowledge, this case report is the first description of postinfarction ventricular septal rupture by the use of cardiac MRI in an intensive care patient with cardiogenic shock and subsequent successful surgical repair.
