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| 1 | Coronary microvascular dysfunction in diabetes mellitus:A review显示文摘The exploration of coronary microcirculatory dysfunction in diabetes has accelerated in recent years.Cardiac function is compromised in diabetes.Diabetic patients manifest accelerated atherosclerosis in coronary arteries.These data are confirmed in diabetic animal mod-els,where lesions of small coronary arteries have been described.These concepts are epitomized in the classic microvascular complications of diabetes,i.e.blindness,kidney failure and distal dry gangrene.Most importantly,accumulating data indicate that insights gained from the link between inflammation and diabetes can yield predictive and prognostic information of considerable clinical utility.This review summarizes the evidence for the predisposing factors and the mechanisms involved in diabetes,and assesses the current state of knowledge regarding the triggers for inflammation in this disease.We evaluate the roles of hyperglycemia,oxidative stress,polyol pathway,protein kinase C,advanced glycation end products,insulin resistance,peroxisome proliferator-activated receptor-γ,inflammation,and diabetic cardiomyopathy as a 'stem cell disease'.Furthermore,we discuss the mechanisms responsible for impaired coronary arteriole function.Finally,we consider how new insights in diabetes may provide innovative therapeutic strategies. | Andrea Picchi Stefano Capobianco Marta Focardi | 2010 | World Journal of Cardiology2010，2，11： | 24 |
| 2 | Vascular endothelial dysfunction and pharmacological treatment显示文摘The endothelium exerts multiple actions involving regulation of vascular permeability and tone, coagulation and fibrinolysis, inflammatory and immunological reactions and cell growth. Alterations of one or more such actions may cause vascular endothelial dysfunction. Different risk factors such as hypercholesterolemia, homocystinemia, hyperglycemia, hypertension, smo-king, inflammation, and aging contribute to the development of endothelial dysfunction. Mechanisms underlying endothelial dysfunction are multiple, including impaired endothelium-derived vasodilators, enhanced endothelium-derived vasoconstrictors, over production of reactive oxygen species and reactive nitrogen species, activation of inflammatory and immune reactions, and imbalance of coagulation and fibrinolysis. Endothelial dysfunction occurs in many cardiovascular diseases, which involves different mechanisms, depending on specific risk factors affecting the disease. Among these mechanisms, a reduction in nitric oxide(NO) bioavailability plays a central role in the development of endothelial dysfunction because NO exerts diverse physiological actions, including vasodilation, anti-inflammation, antiplatelet, antiproliferation and antimigration. Experimental and clinical studies have demonstrated that a variety of currently used or investigational drugs, such as angiotensin-converting enzyme inhibitors, angiotensin AT1 receptors blockers, angiotensin-(1-7), antioxidants, beta-blockers, calcium channel blockers, endothelial NO synthase enhancers, phosphodiesterase 5 inhibitors, sphingosine-1-phosphate and statins, exert endothelial protective effects. Due to the difference in mechanisms of action, these drugs need to be used according to specific mechanisms underlying endothelial dysfunction of the disease. | Jin Bo Su | 2015 | World Journal of Cardiology2015，7，11： | 24 |
| 3 | Vascular dysfunction in diabetes: The endothelial progenitor cells as new therapeutic strategy显示文摘The vascular endothelium is a critical determinant of dia- betes-associated vascular complications, and improving endothelial function is an important target for therapy. Diabetes mellitus contributes to endothelial cell injury and dysfunction. Endothelial progenitor cells (EPCs) play a critical role in maintaining endothelial function and might affect the progression of vascular disease. EPCs are essential to blood vessel formation, can differentiate into mature endothelial cells, and promote the repair of damaged endothelium. In diabetes, the circulating EPC count is low and their functionality is impaired. The me- chanisms that underlie this reduced count and impaired functionality are poorly understood. Knowledge of the status of EPCs is critical for assessing the health of the vascular system, and interventions that increase the number of EPCs and restore their angiogenic activity in diabetes may prove to be particularly beneficial. The pre-sent review outlines current thinking on EPCs' therapeutic potential in endothelial dysfunction in diabetes, as well as evidence-based perspectives regarding their use for vascular regenerative medicine. | Adriana Georgescu | 2011 | World Journal of Diabetes2011，2，6： | 13 |
| 4 | Mechanisms of adaptation of the hepatic vasculature to the deteriorating conditions of blood circulation in liver cirrhosis显示文摘Pub Med, EMBASE, Orphanet, MIDLINE, Google Scholar and Cochrane Library were searched for articles published between 1983 and 2015. Relevant articles were selected by using the following terms: 'Liver cirrhosis', 'Endothelial dysfunction', 'Sinusoidal remodeling', 'Intrahepatic angiogenesis' and 'Pathogenesis of portal hypertension'. Then the reference lists of identified articles were searched for other relevant publications as well. Besides gross hepatic structural disorders related to diffuse fibrosis and formation of regenerative nodules, the complex morphofunctional rearrangement of the hepatic microvascular bed and intrahepatic angiogenesis also play important roles in hemodynamic disturbances in liver cirrhosis. It is characterized by endothelial dysfunction and impaired paracrine interaction between activated stellate hepatocytes and sinusoidal endotheliocytes, sinusoidal remodeling and capillarization, as well as development of the collateral microcirculation. In spite of the fact that complex morphofunctional rearrangement of the hepatic microvascular bed and intrahepatic angiogenesis in liver cirrhosis are the compensatory-adaptive reaction to the deteriorating conditions of blood circulation, they contribute to progression of disease and development of serious complications, in particular, related to portal hypertension.Pub Med,EMBASE,Orphanet,MIDLINE,Google Scholar and Cochrane Library were searched for articles published between 1983 and 2015.Relevant articles were selected by using the following terms:'Liver cirrhosis','Endothelial dysfunction','Sinusoidal remodeling','Intrahepatic angiogenesis'and'Pathogenesis of portal hypertension'.Then the reference lists of identified articles were searched for other relevant publications as well.Besides gross hepatic structural disorders related to diffuse fibrosis and formation of regenerative nodules,the complex morphofunctional rearrangement of the hepatic microvascular bed and intrahepatic angiogenesis also play important roles in hemodynamic disturbances in liver cirrhosis.It is characterized by endothelial dysfunction and impaired paracrine interaction between activated stellate hepatocytes and sinusoidal endotheliocytes,sinusoidal remodeling and capillarization,as well as development of the collateral microcirculation.In spite of the fact that complex morphofunctional rearrangement of the hepatic microvascular bed and intrahepatic angiogenesis in liver cirrhosis are the compensatory-adaptive reaction to the deteriorating conditions of blood circulation,they contribute to progression of disease and development of serious complications,in particular,related to portal hypertension. | Dmitry Victorovich Garbuzenko Nikolay Olegovich Arefyev Dmitry Vladimirovich Belov | 2016 | World Journal of Hepatology2016，8，16： | 11 |
| 5 | Endothelial progenitor cells as factors in neovascularization and endothelial repair显示文摘Endothelial progenitor cells(EPCs)are a heterogeneous population of cells that are provided by the bone marrow and other adult tissue in both animals and humans.They express both hematopoietic and endothelial surface markers,which challenge the classic dogma that the presumed differentiation of cells into angioblasts and subsequent endothelial and vascular differentiation occurred exclusively in embryonic development.This breakthrough stimulated research to understand the mechanism(s)underlying their physiologic function to allow development of new therapeutic options.One focus has been on their ability to form new vessels in injured tissues,and another has been on their ability to repair endothelial damage and restore both monolayer integrity and endothelial function in denuded vessels.Moreover,measures of their density have been shown to be a better predictor of cardiovascular events,both in healthy and coronary artery disease populations than the classical tools used in the clinic to evaluate the risk stratification.In the present paper we review the effects of EPCs on revascularization and endothelial repair in animal models and human studies,in an attempt to better understand their function,which may lead to potential advancement in clinical management. | Stefano Capobianco Venu Chennamaneni Mayank Mittal | 2010 | World Journal of Cardiology2010，2，12： | 7 |
| 6 | Endothelial dysfunction as a predictor of cardiovascular disease in type 1 diabetes显示文摘Macro and microvascular disease are the main cause of morbi-mortality in type 1 diabetes(T1DM).Although there is a clear association between endothelial dysfunction and atherosclerosis in type 2 diabetes,a cause-effect relationship is less clear in T1 DM.Although endothelial dysfunction(ED) precedes atherosclerosis,it is not clear weather,in recent onset T1 DM,it may progress to clinical macrovascular disease.Moreover,endothelial dysfunction may either be reversed spontaneously or in response to intensive glycemic control,long-term exercise training and use of statins.Acute,long-term and post-prandial hyperglycemia as well as duration of diabetes and microalbuminuria are all conditions associated with ED in T1 DM.The pathogenesis of endothelial dysfunction is closely related to oxidative-stress.NAD(P)H oxidase over activity induces excessive superoxide production inside the mitochondrial oxidative chain of endothelial cells,thus reducing nitric oxide bioavailability and resulting in peroxynitrite formation,a potent oxidant agent.Moreover,oxidative stress also uncouples endothelial nitric oxide synthase,which becomes dysfunctional,inducing formation of superoxide.Other important mechanisms are the activation of both the polyol and protein kinase C pathways as well as the presence of advanced glycation end-products.Future studies are needed to evaluate the potential clinical applicability of endothelial dysfunction as a marker for early vascular complications in T1 DM. | Marcello C Bertoluci Gislaine V Cé Antonio MV da Silva Marco V Wainstein Winston Boff Marcia Punales | 2015 | World Journal of Diabetes2015，6，5： | 5 |
| 7 | 胰岛素抵抗: 现在是主要预防的时间?显示文摘 Insulin resistance is a clinical condition characterized by a decrease in sensitivity and responsiveness to the metabolic actions of insulin, so that a given concentration of insulin produces a less-than-expected biological effect. As a result, higher levels of insulin are needed to maintain normal glucose tolerance. Hyperinsulinemia, indeed, is one of the principal characteristics of insulin resistance states. This feature is common in several pathologic conditions, such as type 2 diabetes, obesity, and dyslipidemia, and it is also a prominent component of hypertension, coronary heart disease, and atherosclerosis. The presence of endothelial dysfunction, related to insulin resistance, plays a key role in the development and progression of atherosclerosis in all of these disorders. Insulin resistance represents the earliest detectable abnormality in type 2 diabetes, and is one of the major underlying mechanisms of hypertension and cardiovascular diseases. Its early detection could be of great importance, in order to set a therapeutic attack and to counteract the higher risk of diabetes and cardiovascular diseases. | Valentina Mercurio Guido Carlomagno Valeria Fazio Serafino Fazio | 2012 | World Journal of Cardiology2012，4，1： | 5 |
| 8 | Endothelial and platelet markers in diabetes mellitus type 2显示文摘Diabetes mellitus(DM) is an extremely common disorder which carries a risk of vascular impairment.DM type 2(DM2) can be characterized by the dysfunction of haemostasis manifesting by stimulated coagulation process,disorder of platelet function and decreased fibrinolytic activity.These all are the reasons why DM2 is the most common acquired thrombophilia.Endothelial dysfunction along with platelet hyperactivity are unquestionably involved in the hyperactivation of platelets and clotting factors in DM.As a natural consequence of continuous investigation,many markers of endothelial dysfunction and diabetic thrombocytopathy have been identified and considered for implementation in clinical practice.Endothelial function can be assessed by the evaluation of endothelial markers,circulating molecules synthesised in various amounts by the endothelium.These markers precede the signs of evident microangiopathy.Platelets have an ethiopathogenic relation to the microangiopathy in DM.Their increased activity was confirmed in both types of DM.Predictors of endothelial and platelet disorder could improve the screening of individuals at increased risk,thus leading to the early diagnosis,appropriate treatment,as well as to the effective prevention of the complications of DM2.In the article we deal with the mechanisms involved in the pathogenesis of endothelial and platelet functional abnormalities,endothelial and platelet markers of DM2 considered for implementation in clinical practice and possibilities of their detection. | Peter Kubisz Lucia Staniaková Ján Stako Peter Galajda Marián Mokáň | 2015 | World Journal of Diabetes2015，6，3： | 3 |
| 9 | Coronary microvasculopathy in heart transplantation: Consequences and therapeutic implications显示文摘Despite the progress made in the prevention and treatment of rejection of the transplanted heart, cardiac allograft vasculopathy(CAV) remains the main cause of death in late survival transplanted patients. CAV consists of a progressive diffuse intimal hyperplasia and the proliferation of vascular smooth muscle cells, ending in wall thickening of epicardial vessels, intramyocardial arteries(50-20 μm), arterioles(20-10 μm), and capillaries(< 10 μm). The etiology of CAV remains unclear; both immunologic and non-immunologic mechanisms contribute to endothelial damage with a sustained inflammatory response. The immunological factors involved are Human Leukocyte Antigen compatibility between donor and recipient, alloreactive T cells and the humoral immune system. The non-immunological factors are older donor age, ischemia-reperfusion time, hyperlipidemia and CMV infections. Diagnostic techniques that are able to assess microvascular function are lacking. Intravascular ultrasound and fractional flow reserve, when performed during coronary angiography, are able to detect epicardial coronary artery disease but are not sensitive enough to assess microvascular changes. Some authors have proposed an index of microcircula-tory resistance during maximal hyperemia, which is calculated by dividing pressure by flow(distal pressure multiplied by the hyperemic mean transit time). Non-invasive methods to assess coronary physiology are stress echocardiography, coronary flow reserve by transthoracic Doppler echocardiography, single photon emission computed tomography, and perfusion cardiac magnetic resonance. In this review, we intend to analyze the mechanisms, consequences and therapeutic implications of microvascular dysfunction, including an extended citation of relevant literature data. | Alessandra Vecchiati Sara Tellatin Annalisa Angelini Sabino Iliceto Francesco Tona | 2014 | World Journal of Transplantation2014，4，2： | 3 |
| 10 | Dynamics of circulating microparticles in chronic kidney disease and transplantation:Is it really reliable marker?显示文摘The deterioration of endothelial structure plays a very important role in the development of vascular diseases. It is believed that endothelial dysfunction starts in the early stage of kidney disease and is a risk factor of an unfavorable cardiovascular prognosis. Because a direct assessment of biological states in endothelial cells is not applicable, the measurement of endothelial microparticles(EMPs) detached from endothelium during activation or apoptosis is thought to be a marker of early vascular disease and endothelial dysfunction in children with chronic kidney disease(CKD). Few studies have shown increased circulating EMPs and its relationship with cardiovascular risk factors in patients with CKD.MPs contain membrane proteins and cytosolic material derived from the cell from which they originate. EMPs having CD144, CD 146, CD31+/CD41-, CD51 and CD105 may be used to evaluate the vascular endothelial cell damage and determine asymptomatic patients who might be at higher risk of developing cardiovascular disease in CKD and renal transplant. | Ismail Dursun Sibel Yel Emel Unsur | 2015 | World Journal of Transplantation2015，5，4： | 3 |
| 11 | Impaired coronary microvascular endothelial function in men with metabolic syndrome显示文摘AIM: To assess coronary endothelial function of conduit and resistance vessels in patients with metabolic syndrome (MS). METHODS: Seventy-eight men (mean age, 57 years) with chest pain and angiographically normal coronary arteries were included in the study. Patients with coronary spastic angina were excluded. Changes in coronary artery diameter and coronary blood flow (CBF) in response to acetylcholine (ACh) were determined using quantitative coronary angiography and Doppler velocity measurements. Coronary flow reserve was calculated as the ratio of coronary blood velocity after adenosine triphosphate infusion relative to baseline values. Patients were divided into two groups based on the presence or absence of MS. RESULTS: There were 24 patients in the MS group (31%). The increase in CBF in response to ACh infusion was impaired in the MS group (P < 0.0001) compared to the non-MS group, whereas changes in coronary artery diameter in response to ACh infusion did not differ between the two groups. Multivariate regression analysis revealed that MS was a significant factor associated with the lesser change in CBF induced by ACh infusion at 30 μg/min (P < 0.0001, r 2 = 0.46). CONCLUSION: Coronary endothelial dysfunction was present at the level of resistance vessels but not conduit vessels in the MS patients included in our study. | Hiroki Teragawa Naoya Mitsuba Kenji Nishioka Kentaro Ueda Shingo Kono Yukihito Higashi Kazuaki Chayama Yasuki Kihara | 2010 | World Journal of Cardiology2010，2，7： | 2 |
| 12 | Prognostic value of endothelial dysfunction in type 1 diabetes mellitus显示文摘Patients with diabetes mellitus are at high risk of developing atherosclerosis, associated with higher rates of micro and macro vascular involvement such as coronary artery disease and renal disease. The role of hyperglycemia to induce synthesis of reactive oxygen species by the oxidation of glucose, leading to an increased production of advanced glycosylation end products, as well as inflammation and oxidative stress has been proposed as a possible mechanism in the pathogenesis of endothelial dysfunction(ED). The interaction between C-peptide- the connecting segment of pro-insulin-and nitric oxide in vasodilation is also discussed. Therefore, endothelial dysfunction has been identified as an early marker of vascular disorder in type 1 and type 2 diabetes mellitus. In some other diseases, ED has been considered an independent predictor of vascular disease, regardless of the method used. Studies have demonstrated the importance of endothelial dysfunction as an useful tool for identifying the risk of vascular complications in patients with type 1 diabetes mellitus, particularly as regards to renal impairment. The aim of this review is to clarify the prognostic value of endothelial dysfunction as a marker of vascular disease in these subjects. | Ana Marice Ladeia Raphael Ribeiro Sampaio Maiara CostaHita Luis F Adan | 2014 | World Journal of Diabetes2014，5，5： | 2 |
| 13 | Commutative regulation between endothelial NO synthase and insulin receptor substrate 2 by microRNAs显示文摘Endothelial NO synthase (eNOS) expression is regulated by a number of transcriptional and post-transcriptional mechanisms, but the effects of competing endogenous RNAs (ceRNAs) on eNOS mRNA and the underlying mechanisms are still unknown. Our bioinformatic analysis revealed three highly expressed eNOS-targeting miRNAs (miR-15b, miR-16, and miR-30b) in human endothelial cells (ECs). Among the 1103 mRNA targets of these three miRNAs, 15 mRNAs share a common disease association with eNOS. Gene expression and correlation analysis in patients with cardiovascular diseases identified insulin receptor substrate 2 (IRS2) as the most correlated eNOS-ceRNA. The expression levels of eNOS and IRS2 were coincidentally increased by application of laminar shear but reduced with eNOS or IRS2 siRNA transfection in human ECs, which was impeded by Dicer siRNA treatment. Moreover, luciferase reporter assay showed that these three miRNAs directly target the 3′UTR of eNOS and IRS2. Overexpression of these three miRNAs decreased, whereas inhibition of them increased, both mRNA and protein levels of eNOS and IRS2. Functionally, silencing eNOS suppressed the Akt signal pathway, while IRS2 knockdown reduced NO production in ECs. Thus, we identified eNOS and IRS2 as ceRNAs and revealed a novel mechanism explaining the coincidence of metabolic and cardiovascular diseases. | Xiaoli Sun Huizhen Lv Peng Zhao Jinlong He Qinghua Cui Minxin Wei Shiqing Feng Yi Zhu | 2019 | Journal of Molecular Cell Biology2019，11，6： | 2 |
| 14 | Stem cell therapy for erectile dysfunction显示文摘Erectile dysfunction(ED)is an important health problem that has commonly been clinically treated using phosphodiesterase type 5 inhibitors(PDE5Is).However,PDE5Is are less effective when the structure of the cavernous body has been severely injured,and thus regeneration is required.Stem cell therapy has been investigated as a possible means for regenerating the injured cavernous body.Stem cells are classified into embryonic stem cells and adult stem cells(ASCs),and the intracavernous injection of ASCs has been explored as a therapy in animal ED models.Bone marrowderived mesenchymal stem cells and adipose tissuederived stem cells are major sources of ASCs used for the treatment of ED,and accumulated evidence now suggests that ASCs are useful in the restoration of erectile function and the regeneration of the cavernous body.However,the mechanisms by which ASCs recover erectile function remain controversial.Some studies indicated that ASCs were differentiated into the vascular endothelial cells,vascular smooth muscle cells,and nerve cells that originally resided in the cavernous body,whereas other studies have suggested that ASCs improved erectile function via the secretion of anti-apoptotic and/or proangiogenic cytokines ratherthan differentiation into other cell types.In this paper,we reviewed the characteristics of stem cells used for the treatment of ED,and the possible mechanisms by which these cells exert their effects.We also discussed the problems to be solved before implementation in the clinical setting. | Etsu Suzuki Hiroaki Nishimatsu Yukio Homma | 2014 | World Journal of Clinical Urology2014，3，3： | 2 |
| 15 | miR-101-3p induces vascular endothelial cell dysfunction by targeting tet methylcytosine dioxygenase 2显示文摘Endothelial cell(EC)dysfunction represents an early key event in atherosclerosis.Recently,MicroRNAs have been demonstrated to regulate EC function.miR-101-3p has been discovered to regulate cell apoptosis and proliferation in cardiovascular diseases.Therefore,the aim of the current study was to clarify whether miR-101-3p regulates the dysfunction of vascular endothelial cells.In this study,the transfection of human umbilical vein endothelial cells(HUVECs)with miR-101-3p mimic induced reactive oxygen species(ROS)production,EC dysfunction,and acti-vated nuclear factorB(NF-κB),whereas transfection with miR-101-3p inhibitor alleviated these events.The antioxidant N-acetylcysteine alleviated miR-101-3p-induced EC dysfunction.Moreover,we observed that miR-101-3p inhibited the expression of tet methylcytosine dioxygenase 2(TET2)at the posttranscriptional level,resulting in increased ROS production and activated NF-kB.TET2 overexpression inhibited ROS production,EC dysfunction,and NF-κB activation in miR-101-3p-transfected HUVECs.These results indicate that miR-101-3p induces EC dysfunction by targeting TET2,which regulates ROS production,EC dysfunction,and NF-κB activation.Taken together,our current study reveals a novel pathway associated with EC dysfunction.The modulation of miR-101-3p and TET2 expression levels may serve as a potential target for therapeutic strategies for atherosclerosis. | Qiaoli Chen Xiaoye Li Lingjun Kong Qing Xu Zi Wang Qianzhou Lv | 2020 | Acta Biochimica et Biophysica Sinica2020，52，2： | 2 |
| 16 | Treatment of a patient with congenital analbuminemia with atorvastatin and albumin infusion显示文摘Congenital analbuminemia is a rare autosomic recessive inherited disorder characterized by low plasma albumin and hypercholesterolemia, which may increase cardiovascular risk. Patients are essentially asymptomatic, apart from ease of fatigue, minimal ankle oedema and hypotension. There is no accepted strategy for safely treating both hypercholesterolemia and analbuminemia in order to eventually decrease the atherosclerotic risk. We report a case of congenital analbuminemia(1.0 g/dL) in a 38-year-old male with hypercholesterolemia(range: 406-475 mg/dL) and severe arterial dysfunction [no brachial artery flow-mediated dilation(FMD)]. Long-term, cholesterol-lowering treatment with atorvastatin was associated with the appearance of peripheral edema. Twomonths of infusion with albumin improved FMD(7%) and reduced serum cholesterol(273 mg/dL), supporting the hypothesis of a compensatory role of hypercholesterolemia. Statin treatment, together with periodical albumin infusions, may contribute to the safe reduction of cardiovascular risk. | Maria Del Ben Francesco Angelico Lorenzo Loffredo Francesco Violi | 2013 | World Journal of Clinical Cases2013，1，1： | 1 |
| 17 | Salidroside improves endothelial function and alleviates atherosclerosis by activating a mitochondria-related AMPK/PI3K/Akt/eNOS pathway显示文摘Aim Salidroside (SAL) is a phenylpropanoid glycoside isolated from the medicinal plant Rhodiola rosea. A recent study has reported that SAL can efficiently decrease atherosclerotic plaque formation in low-density lipoprotein receptor - deficient mice. This study was to investigate the molecular mechanism of antiatherogenic effects of SAL. Method Six-week old apoE-/- male mice were fed a high-fat diet for 8 weeks and then were ad- ministered with SAL for another 8 weeks. Atherosclerotic lesion and vascular function were analyzed. Primary cul- tured human umbilical vein endothelial cells (HUVECs) were prepared. Superoxide anion (O2^-), NO produc- tion, mitochondrial membrane potential (△ψm) and intracellular ATP and AMP levels were measured. Expression of eNOS and AMPK were analyzed by Western blot. Result SAL significantly improved endothelial function asso- ciated with increasing eNOS activation thus reduced the atherosclerotic lesion area. SAL increased eNOS-Serl177 phosphorylation and decreased eNOS-Thr495 phosphorylation. SAL significantly activated AMP-activated protein ki- nase (AMPK). Both AMPK inhibitor and AMPK small interfering RNA (siRNA) abolished SAL-induced Akt- Ser473 and eNOS-Serl177 phosphorylation. In contrast, LY294002, the PI3k/Akt pathway inhibitor, abolished SAL-induced phosphorylation and expression of eNOS. SAL decreased cellular ATP content and increased the cel- lular AMP/ATP ratio, which was associated with the activation of AMPK. SAL was found to decrease A^m, which is likely consequence of reduced ATP production. Conclusion The action of SAL to reduce atherosclerotic lesion formation may at least be attributed to its effect on improving endothelial function by promoting nitric oxide (NO) production, which was associated with mitochondria depolarization and subsequent activation of the AMPK/PI3 IC/ Akt/eNOS pathway. Taken together, our data described the effects of SAL on mitochondria, which played critical roles in improving endothelial function in atherosclerosis. | | 2015 | 中国药理学通报2015，31，B11： | 1 |
| 18 | Explaining the increased mortality in type 1 diabetes显示文摘Despite large improvements in the management of glucose levels and in the treatment of cardiovascular risk factors,the mortality rate in individuals with type 1 diabetes(T1D) is still high.Recently,Lind et al found that T1 D individuals with glycated hemoglobin levels of 6.9% or lower had a risk of death from any cause or from cardiovascular causes that is twice as high as the risk for matched controls.T1 D is a chronic disease with an early onset(e.g.,pediatric age) and thus in order to establish a clear correlation between death rate and the glycometabolic control,the whole history of glycemic control should be considered; particularly in the early years of diabetes.The switch from a normoto hyperglycemic milieu in an individual with T1 D in the pediatric age,represents a stressful event that may impact outcomes and death rate many years later.In this paper we will discuss the aforementioned issues,and offer our view on these findings,paying a particular attention to the several alterations occurring in the earliest phases of T1 D and to the many factors that may be associated with the chronic history of T1 D.This may help us to better understand the recently published death rate data and to develop future innovative and effective preventive strategies. | Chiara Mameli Sara Mazzantini Moufida Ben Nasr Paolo Fiorina Andrea E Scaramuzza Gian Vincenzo Zuccotti | 2015 | World Journal of Diabetes2015，6，7： | 1 |
| 19 | G protein-coupled receptor kinase 2 inhibition improves erectile function through amelioration of endothelial dysfunction and oxidative stress in a rat model of type 2 diabetes显示文摘Type 2 diabetes mellitus (T2DM)is a common cause of erectile dysfunction (ED).It has been demonstrated that G protein-coupled receptor kinase 2 (GRK2)overexpression contributes to diabetic endothelial dysfunction and oxidative stress,which also underlies ED in T2DM.We hypothesized that GRK2 overexpressed and attenuated endothelial function of the cavernosal tissue in a rat model of T2DM.T2DM rats were established by feeding with a high-fat diet (HFD)for 2 weeks and then administering two intraperitoneal (IP) injections of a low dose of streptozotocin (STZ),followed by continuous feeding with a HFD for 6 weeks.GRK2 was inhibited by IP injection of paroxetine,a selective GRK2 inhibitor,after STZ injection.Insulin challenge tests,intracavernous pressure (ICP), GRK2 expression,the protein kinase B (Akt)/endothelial nitric oxide synthase (eNOS)pathway,nicotinamide adenine dinucleotide phosphate (NADPH)oxidase subunit gp91phox,nitric oxide (NO),reactive oxygen species (ROS)production,and apoptosis in cavernosal tissue were examined.Less response to insulin injection was observed in T2DM rats 2 weeks after HFD.Markedly increased GRK2 expression,along with impaired Akt/eNOS pathway,reduced NO production,increased gp91phox expression and ROS generation,increased apoptosis and impaired erectile function were found in T2DM rats.inhibition of GRK2 with paroxetine ameliorated Akt/eNOS signaling,restored NO production,downregulated NADPH oxidase,subsequently inhibited ROS generation and apoptosis,and ultimately preserved erectile function.These results indicated that GRK2 upregulation may be an important mechanism underlying T2DM ED,and GRK2 inhibition may be a potential therapeutic strategy for T2DM ED. | Zhi-Hua Wan Yuan-Jie Zhang Lin Chen Yong-Lian Guo Guo-Hao Li Ding Wu Yong Wang | 2019 | Asian Journal of Andrology2019，21，1： | 1 |
| 20 | von Willebrand factor antigen as a therapeutic target of portal hypertension in cirrhosis显示文摘Increased thrombotic potential within the liver sinusoids due to local endothelial production of von Willebrand factor antigen macromolecules could represent an additional therapeutic target of portal hypertension in patients with cirrhosis. In this case, anti-inflammatory and antithrombotic drugs could modulate portal pressure by preventing the formation of intrahepatic platelet-induced microthrombi. | Georgios N Kalambokis Gerasimos Baltayiannis Dimitrios Christodoulou | 2016 | World Journal of Gastroenterology2016，22，19： | 1 |
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