目的探讨抑郁障碍对慢性收缩性心力衰竭患者血浆中分泌型ST2（sST2）和神经激素（NT—proBNP与Gh—relin）水平及其预后的影响。方法纳入射血分数≤40％，平均年龄（60±12）岁的146例心衰患者，分别接受医院焦虑抑郁量表（HADS）...目的探讨抑郁障碍对慢性收缩性心力衰竭患者血浆中分泌型ST2（sST2）和神经激素（NT—proBNP与Gh—relin）水平及其预后的影响。方法纳入射血分数≤40％，平均年龄（60±12）岁的146例心衰患者，分别接受医院焦虑抑郁量表（HADS）、汉密尔顿抑郁量表（HAMD）、汉密尔顿焦虑量表（HAMA）和明尼苏达心力衰竭生活质量量表（ML-HFQ）的评估，并测定血浆sST2、NT-proBNP和Ghrelin水平。所有患者随访9个月，初级终点是全因死亡和因心衰再次住院。结果与心衰无抑郁障碍组患者相比，心衰合并抑郁障碍的患者（52例，35．6％）血浆sST2水平（55．3ng／mL％41．1ng／mL，P％0．01）和NT—proBNP水平（5886pg／mL＂US．2682pg／mL，P％0．01）显著增高，而Ghrelin水平降低（7．0ng／mL7dS．7．9ng／mL，P=0．041）。sST2和NT—proBNP水平与抑郁障碍独立相关。9个月随访期间抑郁障碍组全因死亡率（32．7％VS．7．4％，P％0．01）和因心衰再住院率（48．1％ vs 27．7％，P〈0．01）显著高于无抑郁障碍组。多因素Cox回归分析显示在校正临床相关变量后抑郁障碍（HR2．24，95％ CI 1．18～4．25，P=0．014）仍是心衰患者全因死亡和心衰再住院的独立危险因素。伴抑郁障碍且sST2〉45．1ng／mL或NT—proBNP〉3286pg／mL的心衰患者全因死亡和心衰再住院的风险显著增加。结论心衰伴抑郁障碍的患者血浆sST2和NT—proBNP水平增高，Ghrelin水平降低。抑郁障碍联合sST2或NT-proBNP对心衰患者不良预后有较高的预测价值。展开更多
Summary： Angiogenic gene therapy and cell-based therapy for peripheral arterial disease （PAD） have been studied intensively currently. This study aimed to investigate whether combining mesenchymal stem cells （MSCs...Summary： Angiogenic gene therapy and cell-based therapy for peripheral arterial disease （PAD） have been studied intensively currently. This study aimed to investigate whether combining mesenchymal stem cells （MSCs）transplantation with ex vivo human hepatocyte growth factor （HGF） gene transfer was more therapeutically efficient than the MSCs therapy alone in a rat model of hindlimb ischemia. One week after establishing hindlimb ischemia models, Sprague-Dawley （SD） rats were randomized to receive HGF gene-modified MSCs transplantation （HGF-MSC group）, untreated MSCs transplantation （MSC group）, or PBS injection （PBS group）, respectively. Three weeks after injection, angiogenesis was significantly induced by both MSCs and HGF-MSCs transplantation, and capillary density was the highest in the HGF-MSC group. The number of transplanted cell-derived endothelial cells was greater in HGF-MSC group than in MSC group after one week treatment. The expression of angiogenic cytokines such as HGF and VEGF in local ischemic muscles was more abundant in HGF-MSC group than in the other two groups. In vitro, the conditioned media obtained from HGF-MSCs cultures exerted proproliferative and promigratory effects on endothelial cells. It is concluded that HGF gene-modified MSCs transplantation therapy may induce more potent angiogenesis than the MSCs therapy alone. Engraftment of MSCs combined with angiogenic gene delivery may be a promising therapeutic strategy for the treatment of severe PAD.展开更多
Myocardial ischemia–reperfusion injury(MIRI)is a major hindrance to the success of cardiac reperfusion therapy.Although increased neutrophil infiltration is a hallmark of MIRI,the subtypes and alterations of neutroph...Myocardial ischemia–reperfusion injury(MIRI)is a major hindrance to the success of cardiac reperfusion therapy.Although increased neutrophil infiltration is a hallmark of MIRI,the subtypes and alterations of neutrophils in this process remain unclear.Here,we performed single-cell sequencing of cardiac CD45^(+)cells isolated from the murine myocardium subjected to MIRI at six-time points.We identified diverse types of infiltrating immune cells and their dynamic changes during MIRI.Cardiac neutrophils showed the most immediate response and largest changes and featured with functionally heterogeneous subpopulations,including Ccl3^(hi)Neu and Ym-1^(hi)Neu,which were increased at 6 h and 1 d after reperfusion,respectively.Ym-1^(hi)Neu selectively expressed genes with protective effects and was,therefore,identified as a novel specific type of cardiac cell in the injured heart.Further analysis indicated that neutrophils and their subtypes orchestrated subsequent immune responses in the cardiac tissues,especially instructing the response of macrophages.The abundance of Ym-1^(hi)Neu was closely correlated with the therapeutic efficacy of MIRI when neutrophils were specifically targeted by anti-Lymphocyte antigen 6 complex locus G6D(Ly6G)or anti-Intercellular cell adhesion molecule-1(ICAM-1)neutralizing antibodies.In addition,a neutrophil subtype with the same phenotype as Ym-1^(hi)Neu was detected in clinical samples and correlated with prognosis.Ym-1 inhibition exacerbated myocardial injury,whereas Ym-1 supplementation significantly ameliorated injury in MIRI mice,which was attributed to the tilt of Ym-1 on the polarization of macrophages toward the repair phenotype in myocardial tissue.Overall,our findings reveal the antiinflammatory phenotype of Ym-1^(hi)Neu and highlight its critical role in myocardial protection during the early stages of MIRI.展开更多
文摘目的探讨抑郁障碍对慢性收缩性心力衰竭患者血浆中分泌型ST2（sST2）和神经激素（NT—proBNP与Gh—relin）水平及其预后的影响。方法纳入射血分数≤40％，平均年龄（60±12）岁的146例心衰患者，分别接受医院焦虑抑郁量表（HADS）、汉密尔顿抑郁量表（HAMD）、汉密尔顿焦虑量表（HAMA）和明尼苏达心力衰竭生活质量量表（ML-HFQ）的评估，并测定血浆sST2、NT-proBNP和Ghrelin水平。所有患者随访9个月，初级终点是全因死亡和因心衰再次住院。结果与心衰无抑郁障碍组患者相比，心衰合并抑郁障碍的患者（52例，35．6％）血浆sST2水平（55．3ng／mL％41．1ng／mL，P％0．01）和NT—proBNP水平（5886pg／mL＂US．2682pg／mL，P％0．01）显著增高，而Ghrelin水平降低（7．0ng／mL7dS．7．9ng／mL，P=0．041）。sST2和NT—proBNP水平与抑郁障碍独立相关。9个月随访期间抑郁障碍组全因死亡率（32．7％VS．7．4％，P％0．01）和因心衰再住院率（48．1％ vs 27．7％，P〈0．01）显著高于无抑郁障碍组。多因素Cox回归分析显示在校正临床相关变量后抑郁障碍（HR2．24，95％ CI 1．18～4．25，P=0．014）仍是心衰患者全因死亡和心衰再住院的独立危险因素。伴抑郁障碍且sST2〉45．1ng／mL或NT—proBNP〉3286pg／mL的心衰患者全因死亡和心衰再住院的风险显著增加。结论心衰伴抑郁障碍的患者血浆sST2和NT—proBNP水平增高，Ghrelin水平降低。抑郁障碍联合sST2或NT-proBNP对心衰患者不良预后有较高的预测价值。
基金supported by a grant from the National Natural Science Foundation of China(No.30470457)
文摘Summary： Angiogenic gene therapy and cell-based therapy for peripheral arterial disease （PAD） have been studied intensively currently. This study aimed to investigate whether combining mesenchymal stem cells （MSCs）transplantation with ex vivo human hepatocyte growth factor （HGF） gene transfer was more therapeutically efficient than the MSCs therapy alone in a rat model of hindlimb ischemia. One week after establishing hindlimb ischemia models, Sprague-Dawley （SD） rats were randomized to receive HGF gene-modified MSCs transplantation （HGF-MSC group）, untreated MSCs transplantation （MSC group）, or PBS injection （PBS group）, respectively. Three weeks after injection, angiogenesis was significantly induced by both MSCs and HGF-MSCs transplantation, and capillary density was the highest in the HGF-MSC group. The number of transplanted cell-derived endothelial cells was greater in HGF-MSC group than in MSC group after one week treatment. The expression of angiogenic cytokines such as HGF and VEGF in local ischemic muscles was more abundant in HGF-MSC group than in the other two groups. In vitro, the conditioned media obtained from HGF-MSCs cultures exerted proproliferative and promigratory effects on endothelial cells. It is concluded that HGF gene-modified MSCs transplantation therapy may induce more potent angiogenesis than the MSCs therapy alone. Engraftment of MSCs combined with angiogenic gene delivery may be a promising therapeutic strategy for the treatment of severe PAD.
基金supported by the National Natural Science Foundation of China(82022076,81974249,82070136,82104488,and 82305194)the Postdoctoral Science Foundation of China(2023M731222,and 2020T130040ZX)the Foundation of Hubei Key Laboratory of Biological Targeted Therapy(2023swbx021)。
文摘Myocardial ischemia–reperfusion injury(MIRI)is a major hindrance to the success of cardiac reperfusion therapy.Although increased neutrophil infiltration is a hallmark of MIRI,the subtypes and alterations of neutrophils in this process remain unclear.Here,we performed single-cell sequencing of cardiac CD45^(+)cells isolated from the murine myocardium subjected to MIRI at six-time points.We identified diverse types of infiltrating immune cells and their dynamic changes during MIRI.Cardiac neutrophils showed the most immediate response and largest changes and featured with functionally heterogeneous subpopulations,including Ccl3^(hi)Neu and Ym-1^(hi)Neu,which were increased at 6 h and 1 d after reperfusion,respectively.Ym-1^(hi)Neu selectively expressed genes with protective effects and was,therefore,identified as a novel specific type of cardiac cell in the injured heart.Further analysis indicated that neutrophils and their subtypes orchestrated subsequent immune responses in the cardiac tissues,especially instructing the response of macrophages.The abundance of Ym-1^(hi)Neu was closely correlated with the therapeutic efficacy of MIRI when neutrophils were specifically targeted by anti-Lymphocyte antigen 6 complex locus G6D(Ly6G)or anti-Intercellular cell adhesion molecule-1(ICAM-1)neutralizing antibodies.In addition,a neutrophil subtype with the same phenotype as Ym-1^(hi)Neu was detected in clinical samples and correlated with prognosis.Ym-1 inhibition exacerbated myocardial injury,whereas Ym-1 supplementation significantly ameliorated injury in MIRI mice,which was attributed to the tilt of Ym-1 on the polarization of macrophages toward the repair phenotype in myocardial tissue.Overall,our findings reveal the antiinflammatory phenotype of Ym-1^(hi)Neu and highlight its critical role in myocardial protection during the early stages of MIRI.
