BACKGROUND Peripheral arterial disease(PAD)has become one of the leading causes of disability and death in diabetic patients.Restoring blood supply to the hindlimbs,especially by promoting arteriogenesis,is currently ...BACKGROUND Peripheral arterial disease(PAD)has become one of the leading causes of disability and death in diabetic patients.Restoring blood supply to the hindlimbs,especially by promoting arteriogenesis,is currently the most effective strategy,in which endothelial cells play an important role.Tongxinluo(TXL)has been widely used for the treatment of cardio-cerebrovascular diseases and extended for diabetes-related vascular disease.AIM To investigate the effect of TXL on diabetic PAD and its underlying mechanisms.METHODS An animal model of diabetic PAD was established by ligating the femoral artery of db/db mice.Laser Doppler imaging and micro-computed tomography(micro-CT)were performed to assess the recovery of blood flow and arteriogenesis.Endothelial cell function related to arteriogenesis and cellular pyroptosis was assessed using histopathology,Western blot analysis,enzyme-linked immunosorbent assay and real-time polymerase chain reaction assays.In vitro,human vascular endothelial cells(HUVECs)and human vascular smooth muscle cells(VSMCs)were pretreated with TXL for 4 h,followed by incubation in high glucose and hypoxia conditions to induce cell injury.Then,indicators of HUVEC pyroptosis and function,HUVECVSMC interactions and the migration of VSMCs were measured.RESULTS Laser Doppler imaging and micro-CT showed that TXL restored blood flow to the hindlimbs and enhanced arteriogenesis.TXL also inhibited endothelial cell pyroptosis via the reactive oxygen species/nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3/Caspase-1/GSDMD signaling pathway.In addition,TXL restored endothelial cell functions,including maintaining the balance of vasodilation,acting as a barrier to reduce inflammation,and enhancing endothelial-smooth muscle cell interactions through the Jagged-1/Notch-1/ephrin-B2 signaling pathway.Similar results were observed in vitro.CONCLUSION TXL has a pro-arteriogenic effect in the treatment of diabetic PAD,and the mechanism may be related to the inhibition of endothelial cell pyroptosis,restoration of endothelial cell function and promotion of endothelial cell-smooth muscle cell interactions.展开更多
Isometric exercise(IE)is a promising intervention of noninvasive revascularization in patients with acute myocardial infarction(AMI).This study aimed to investigate the impact and mechanisms of IE training on arteriog...Isometric exercise(IE)is a promising intervention of noninvasive revascularization in patients with acute myocardial infarction(AMI).This study aimed to investigate the impact and mechanisms of IE training on arteriogenesis in AMI.Male Sprague-Dawley rats were randomly assigned into the sham-operation group(SO),myocardial infarction(MI)group,and 13 IE subgroups treated according to training intensity,frequency,duration,or monocyte chemoattractant protein-1(MCP-1),or/and fibroblast growth factor-2(FGF-2)inhibitors for eight weeks.Our results demonstrated that the IE group achieved superior improvement compared with the MI group in terms of left ventricular ejection fraction(LVEF),myocardial infarction size(MIS),arterial density(AD),monocytes(MNCs),smooth muscle cells(SMCs),endothelial cells(ECs),relative collateral blood flow(RCBF),MCP-1,and FGF-2 at the endpoint.Positive correlations between MCP-1 and MNCs,MNCs and FGF-2,FGF-2 and SMCs,SMCs and AD,as well as AD and RCBF were observed.This study demonstrated that with MI of 100%load 20 times daily for eight weeks,the arteriogenesis was improved,which may be attributed to the recruitment of MNCs and SMCs in remote ischemic myocardium caused by increases in MCP-1 and FGF-2 expression.展开更多
With the high incidence of diabetes around the world,ischemic complications cause a serious influence on people’s production and living.Neovascularization plays a significant role in its development.Therefore,neovasc...With the high incidence of diabetes around the world,ischemic complications cause a serious influence on people’s production and living.Neovascularization plays a significant role in its development.Therefore,neovascularization after diabetic ischemia has aroused attention and has become a hot spot in recent years.Neovascularization is divided into angiogenesis represented by atherosclerosis and arteriogenesis characterized by coronary collateral circulation.When mononuclear macrophages successively migrate to the ischemia anoxic zone after ischemia or hypoxia,they induce the secretion of cytokines,such as vascular endothelial growth factor and hypoxia-inducible factor,activate signaling pathways such as classic Wnt and phosphatidylinositol 3 kinase(PI3K)/protein kinase B(Akt)pathways,trigger oxidative stress response,activate endothelial progenitor cells or enter the glycolysis or lactic acid process and promote the formation of new blood vessels,remodeling them into mature blood vessels and restoring blood supply.However,the hypoglycemic condition has different impacts on neovascularization.Consequently,this review aimed to introduce the mechanisms of neovascularization after diabetic ischemia,increase our understanding of diabetic ischemic complications and their therapies and provide more treatment options for clinical practice and effectively relieve patients’pain.It is believed that in the near future,neovascularization will bring more benefits and hope to patients with diabetes.展开更多
The myocardium adapts to ischemic insults in a variety of ways.One adaptation is the phenomenon of acute preconditioning,which can greatly ameliorate ischemic damage.However,this effect wanes within a few hours and do...The myocardium adapts to ischemic insults in a variety of ways.One adaptation is the phenomenon of acute preconditioning,which can greatly ameliorate ischemic damage.However,this effect wanes within a few hours and does not confer chronic protection.A more chronic adaptation is the so-called second window of preconditioning,which enables protection for a few days.The most potent adaptation invoked by the myocardium to minimize the effects of ischemia is the growth of blood vessels in the heart,angiogenesis and arteriogenesis (collateral growth),which prevent the development of ischemia by enabling flow to a jeopardized region of the heart.This brief review examines the mechanisms underlying angiogenesis and arteriogenesis in the heart.The concept of a redox window,which is an optimal redox state for vascular growth,is discussed along with signaling mechanisms invoked by reactive oxygen species that are stimulated during ischemia-reperfusion.Finally,the review discusses of some of the pathologies,especially the metabolic syndrome,that negatively affect collateral growth through the corruption of redox signaling processes.展开更多
Accumulative evidences have underpinned the nature candidates from Chinese medicine （CM）, particularly CM served as blood activating and stasis resolving （BASR, Huoxue Huayu in Chinese） by targeting tumor-associat...Accumulative evidences have underpinned the nature candidates from Chinese medicine （CM）, particularly CM served as blood activating and stasis resolving （BASR, Huoxue Huayu in Chinese） by targeting tumor-associated angiogenesis. However, recent experiment research on the therapeutic angiogenesis by BASR-CM attracts wide attention and discussion. This opinion review focused on the underlying link between two indications and anticipated that （1） BASR-CM might emphasize on a balanced multi-cytokines network interaction; （2） BASR-CM might address on the nature of diseases prior to differently affecting physiological and pathological angiogenesis; （3） BASR-CM might mainly act on perivascular cells, either promotes arteriogenesis by increasing arteriogenic factors in ischemic diseases, or simultaneously keep a quiescent vasculature to impede angiogenesis in tumor context.展开更多
基金Supported by The Hebei Province Natural Science Foundation,No. H2019106062Key R&D Plan of Hebei Provincial Department of Science and Technology,No. 223777155DResearch Project of Hebei Provincial Administration of Traditional Chinese Medicine,No. 2023179
文摘BACKGROUND Peripheral arterial disease(PAD)has become one of the leading causes of disability and death in diabetic patients.Restoring blood supply to the hindlimbs,especially by promoting arteriogenesis,is currently the most effective strategy,in which endothelial cells play an important role.Tongxinluo(TXL)has been widely used for the treatment of cardio-cerebrovascular diseases and extended for diabetes-related vascular disease.AIM To investigate the effect of TXL on diabetic PAD and its underlying mechanisms.METHODS An animal model of diabetic PAD was established by ligating the femoral artery of db/db mice.Laser Doppler imaging and micro-computed tomography(micro-CT)were performed to assess the recovery of blood flow and arteriogenesis.Endothelial cell function related to arteriogenesis and cellular pyroptosis was assessed using histopathology,Western blot analysis,enzyme-linked immunosorbent assay and real-time polymerase chain reaction assays.In vitro,human vascular endothelial cells(HUVECs)and human vascular smooth muscle cells(VSMCs)were pretreated with TXL for 4 h,followed by incubation in high glucose and hypoxia conditions to induce cell injury.Then,indicators of HUVEC pyroptosis and function,HUVECVSMC interactions and the migration of VSMCs were measured.RESULTS Laser Doppler imaging and micro-CT showed that TXL restored blood flow to the hindlimbs and enhanced arteriogenesis.TXL also inhibited endothelial cell pyroptosis via the reactive oxygen species/nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3/Caspase-1/GSDMD signaling pathway.In addition,TXL restored endothelial cell functions,including maintaining the balance of vasodilation,acting as a barrier to reduce inflammation,and enhancing endothelial-smooth muscle cell interactions through the Jagged-1/Notch-1/ephrin-B2 signaling pathway.Similar results were observed in vitro.CONCLUSION TXL has a pro-arteriogenic effect in the treatment of diabetic PAD,and the mechanism may be related to the inhibition of endothelial cell pyroptosis,restoration of endothelial cell function and promotion of endothelial cell-smooth muscle cell interactions.
基金supported by the research grants from the National Natural Science Foundation of China(Grant No.8177244,No.81902288,and No.82072546)Nanjing Municipal Science and Technology Bureau(Grant No.2019060002).
文摘Isometric exercise(IE)is a promising intervention of noninvasive revascularization in patients with acute myocardial infarction(AMI).This study aimed to investigate the impact and mechanisms of IE training on arteriogenesis in AMI.Male Sprague-Dawley rats were randomly assigned into the sham-operation group(SO),myocardial infarction(MI)group,and 13 IE subgroups treated according to training intensity,frequency,duration,or monocyte chemoattractant protein-1(MCP-1),or/and fibroblast growth factor-2(FGF-2)inhibitors for eight weeks.Our results demonstrated that the IE group achieved superior improvement compared with the MI group in terms of left ventricular ejection fraction(LVEF),myocardial infarction size(MIS),arterial density(AD),monocytes(MNCs),smooth muscle cells(SMCs),endothelial cells(ECs),relative collateral blood flow(RCBF),MCP-1,and FGF-2 at the endpoint.Positive correlations between MCP-1 and MNCs,MNCs and FGF-2,FGF-2 and SMCs,SMCs and AD,as well as AD and RCBF were observed.This study demonstrated that with MI of 100%load 20 times daily for eight weeks,the arteriogenesis was improved,which may be attributed to the recruitment of MNCs and SMCs in remote ischemic myocardium caused by increases in MCP-1 and FGF-2 expression.
基金Supported by the National Natural Science Foundation of China,No.82070455the Related Foundation of Jiangsu Province,No.BK20201225+1 种基金the Medical Innovation Team Project of Jiangsu Province,No.CXTDA2017010the Postgraduate Research and Practice Innovation Program of Jiangsu Province,No.KYCX20_3051.
文摘With the high incidence of diabetes around the world,ischemic complications cause a serious influence on people’s production and living.Neovascularization plays a significant role in its development.Therefore,neovascularization after diabetic ischemia has aroused attention and has become a hot spot in recent years.Neovascularization is divided into angiogenesis represented by atherosclerosis and arteriogenesis characterized by coronary collateral circulation.When mononuclear macrophages successively migrate to the ischemia anoxic zone after ischemia or hypoxia,they induce the secretion of cytokines,such as vascular endothelial growth factor and hypoxia-inducible factor,activate signaling pathways such as classic Wnt and phosphatidylinositol 3 kinase(PI3K)/protein kinase B(Akt)pathways,trigger oxidative stress response,activate endothelial progenitor cells or enter the glycolysis or lactic acid process and promote the formation of new blood vessels,remodeling them into mature blood vessels and restoring blood supply.However,the hypoglycemic condition has different impacts on neovascularization.Consequently,this review aimed to introduce the mechanisms of neovascularization after diabetic ischemia,increase our understanding of diabetic ischemic complications and their therapies and provide more treatment options for clinical practice and effectively relieve patients’pain.It is believed that in the near future,neovascularization will bring more benefits and hope to patients with diabetes.
基金Supported by National Institute of Health Grants No.HL32788, R01 83366,RC1HL100828(to Chilian WM)an American Heart Association Post-doctoral Fellowship,No.09POST2290021 (to Pung YF)
文摘The myocardium adapts to ischemic insults in a variety of ways.One adaptation is the phenomenon of acute preconditioning,which can greatly ameliorate ischemic damage.However,this effect wanes within a few hours and does not confer chronic protection.A more chronic adaptation is the so-called second window of preconditioning,which enables protection for a few days.The most potent adaptation invoked by the myocardium to minimize the effects of ischemia is the growth of blood vessels in the heart,angiogenesis and arteriogenesis (collateral growth),which prevent the development of ischemia by enabling flow to a jeopardized region of the heart.This brief review examines the mechanisms underlying angiogenesis and arteriogenesis in the heart.The concept of a redox window,which is an optimal redox state for vascular growth,is discussed along with signaling mechanisms invoked by reactive oxygen species that are stimulated during ischemia-reperfusion.Finally,the review discusses of some of the pathologies,especially the metabolic syndrome,that negatively affect collateral growth through the corruption of redox signaling processes.
基金Supported by the National Natural Science Foundation of China(Nos.81173174,81403260 and 81573859)China Post-doctoral Science Foundation(No.2014M551639)+4 种基金Natural Science Foundation of Jiangsu Province(No.BK2012854)Postdoctoral Funding in Jiangsu Province(No.1401138C)2013 Program for Excellent Scientific and Technological Innovation Team of Jiangsu Higher Education(No.PPZY2015A070)the Priority Academic Program Development of Jiangsu Higher Education InstitutionsJiangsu College Graduate Research and Innovation Projects(No.CXZZ13_0627)
文摘Accumulative evidences have underpinned the nature candidates from Chinese medicine （CM）, particularly CM served as blood activating and stasis resolving （BASR, Huoxue Huayu in Chinese） by targeting tumor-associated angiogenesis. However, recent experiment research on the therapeutic angiogenesis by BASR-CM attracts wide attention and discussion. This opinion review focused on the underlying link between two indications and anticipated that （1） BASR-CM might emphasize on a balanced multi-cytokines network interaction; （2） BASR-CM might address on the nature of diseases prior to differently affecting physiological and pathological angiogenesis; （3） BASR-CM might mainly act on perivascular cells, either promotes arteriogenesis by increasing arteriogenic factors in ischemic diseases, or simultaneously keep a quiescent vasculature to impede angiogenesis in tumor context.
