Atherosclerosis is driven by metabolic dysregulation and endothelial dysfunction; however, the precise molecular mechanisms underlying its pathogenesis remain incompletely elucidated. Fibrinogen-like protein 1 (FGL1) is a well-established hepatokine with critical roles in regulating tumorigenesis and metabolic dysfunction, while its involvement in atherogenesis remains unclear. Our clinical and preclinical studies revealed elevated plasma FGL1 levels in atherosclerotic patients and mice, correlating with arterial stenosis severity. Prolonged high-fat diet exposure specifically upregulated hepatic FGL1 expression. Hepatic FGL1 overexpression accelerated atherosclerosis, while liver-specific knockdown reduced plaque burden. Exogenous administration of FGL1 accelerated endothelial injury and atherosclerosis progression. Mechanistically, liver-derived FGL1 accumulates in vascular endothelium through fibrinogen C-terminal domain Trp225-mediated binding to integrin β1's vWFA domain. This interaction promotes the conformational change of integrin β1 and the formation of integrin β1/ILK1 complex, co-activating FAK/ERK and Smad signaling to drive transcriptional reprogramming of endothelial cells. Therapeutic interventions targeting FGL1–integrin β1 axis by integrin β1 blocking antibody, FGL1-neutralizing antibody, or RGD peptide effectively attenuated endothelial injury and atherogenic progression in murine models. These findings establish hepatic FGL1 as a novel endocrine regulator of vascular pathophysiology, highlighting the FGL1–integrin β1 axis as a promising therapeutic target for endothelial protection and atherosclerosis management.

In hypertrophic and failing hearts, fuel metabolism is reprogrammed toward enhanced glycolysis. Here, we identify asprosin, an adipokine, as a critical regulator of this process in pathological cardiac hypertrophy. In patients, circulating asprosin levels correlate with NT-proBNP and EF. Cardiomyocyte-specific asprosin overexpression aggravates hypertrophy, abnormal glycolysis, and impairs mitochondrial ATP production in male mice, whereas its deficiency confers protection against TAC- or Ang II-induced remodeling in male/female mice. Mechanistically, asprosin binds PFKP and inhibits the K48-linked ubiquitination by DTX3L, thereby stabilizing PFKP and driving aberrant glycolysis, PDK4 induction, PDH inhibition, and impaired respiration. Genetic knockdown of PFKP mitigates hypertrophy and fibrosis in male mice, whereas PFKP overexpression abolishes the protective effects conferred by FBN1 knockdown. Moreover, YY1 is identified as a transcriptional activator of asprosin in the hypertrophic hearts of male mice. Here we show that the YY1-asprosin-PFKP-PDK4-PDH axis underlies metabolic remodeling, and we highlight plasma asprosin as a potential early biomarker and therapeutic target for cardiac dysfunction.

Alterations in liver metabolism play a pivotal role in the development and progression of metabolic dysfunction-associated steatotic liver disease (MASLD). Asprosin is reported to be released from white adipose tissue during fasting and targets the liver. However, the role of asprosin, especially from organs other than adipose tissue, in MASLD remains poorly understood. These findings demonstrate that plasma asprosin levels are significantly elevated in MASLD patients and animal models. Additionally, asprosin expression increased in the liver of MASLD mice. Hepatocyte-specific overexpression of asprosin impairs mitochondrial fatty acid β-oxidation (FAO), whereas its knockdown not only enhances FAO in mice but also compensates for fenofibrate's limitations in MASLD treatment. Mechanistic investigations reveal that the interaction of asprosin with FABP5 facilitates its abnormal nuclear localization, and asprosin directly bound to and inhibites peroxisome proliferator-activated receptor elements (PPREs), which negatively regulated PPARα transcriptional activity, and disrupts hepatic FAO pathways. GalNAc-siRNAs targeting hepatic FABP5 ameliorate hepatic steatosis. These findings reveal that the secretory adipose factor asprosin is expected to act as a biological marker for early clinical diagnosis and prognostic evaluation of MASLD. Moreover, targeting hepatic asprosin gene inhibition and GalNAc-siRNAs to inhibit hepatic FABP5 both offer potential therapeutic benefits in the treatment of MASLD.

Restenosis after angioplasty is caused usually by neointima formation characterized by aberrant vascular smooth muscle cell (VSMC) dedifferentiation. Myeloid-derived growth factor (MYDGF), secreted from bone marrow-derived monocytes and macrophages, has been found to have cardioprotective effects. In this study we investigated the effect of MYDGF to postinjury neointimal formation and the underlying mechanisms. Rat carotid arteries balloon-injured model was established. We found that plasma MYDGF content and the level of MYDGF in injured arteries were significantly decreased after balloon injury. Local application of exogenous MYDGF (50 μg/mL) around the injured vessel during balloon injury markedly ameliorated the development of neointimal formation evidenced by relieving the narrow endovascular diameter, improving hemodynamics, and reducing collagen deposition. In addition, local application of MYDGF inhibited VSMC dedifferentiation, which was proved by reversing the elevated levels of osteopontin (OPN) protein and decreased levels of α-smooth muscle actin (α-SMA) in the left carotid arteries. We showed that PDGF-BB (30 ng/mL) stimulated VSMC proliferation, migration and dedifferentiation in vitro; pretreatment with MYDGF (50−200 ng/mL) concentration-dependently eliminated PDGF-BB-induced cell proliferation, migration and dedifferentiation. Molecular docking revealed that MYDGF had the potential to bind with sphingosine-1-phosphate receptor 2 (S1PR2), which was confirmed by SPR assay and Co-IP analysis. Pretreatment with CCG-1423 (Rho signaling inhibitor), JTE-013 (S1PR2 antagonist) or Ripasudil (ROCK inhibitor) circumvented the inhibitory effects of MYDGF on VSMC phenotypic switching through inhibiting S1PR2 or its downstream RhoA-actin monomers (G-actin) /actin filaments (F-actin)-MRTF-A signaling. In summary, this study proves that MYDGF relieves neointimal formation of carotid arteries in response to balloon injury in rats, and suppresses VSMC dedifferentiation induced by PDGF-BB via S1PR2-RhoA-G/F-actin-MRTF-A signaling pathway. In addition, our results provide evidence for cross talk between bone marrow and vasculature.

Background: Circular non-coding RNA (circRNA) has a variety of biological functions. However, the expression profile and potential effects of circRNA on atherosclerosis (AS) and vascular endothelial injury have not been fully elucidated. This study aims to identify the differentially expressed circRNAs in atherosclerotic aortic vessels and predict their potential functions in endothelial injury. Method: ApoE-/- mice were fed with high-fat diet for 12 weeks to induce AS. Atherosclerotic plaques were evaluated by H&E and Masson staining and immunohistochemistry; differentially expressed circRNAs were detected by Arraystar Circular RNA Microarray and verified by RT-PCR; the potential target mircoRNAs of circRNAs were predicted by miRanda, Tarbase, Targetscan and their expression changes were verified by RT-PCR; the potential target genes of mircoRNAs were predicted by Targetscan and verified by Western blot; the signaling pathways that they might annotate or regulate and their potential functions in vascular endothelial injury were predicted by gene enrichment analysis. Results: Fifty two circRNAs were up-regulated more than twice and 47 circRNAs were down-regulated more than 1.5 times in AS aortic vessels. Mmmu_circRNA_36781 and 37699 were up-regulated both in AS aortic vessels and H2O2-treated mouse aortic endothelial cells (MAECs). The expression of miR-30d-3p and miR-140-3p, the target microRNA of circRNA_37699 and circRNA_36781, were downregulated both in AS vessels and H2O2-treated MAECs. On the contrary, MKK6 and TP53RK, the potential target gene of miR-140-3p and miR-30d-3p, were upregulated both in AS aortic roots and H2O2-treated MAECs. Besides, gene enrichment analysis showed that MAPK and PI3K-AKT signaling pathway were the most potential signaling pathways regulated by the differentially expressed circRNAs in atherosclerosis. Conclusions: Mmu_circRNA_36781 (circRNA ABCA1) and 37699 (circRNA KHDRBS1) were significantly up-regulated in AS aortic vessels and H2O2-treated MAECs. They have potential regulatory effects on atherosclerosis and vascular endothelial injury by targeting miR-30d-3p-TP53RK and miR-140-3p-MKK6 axis and their downstream signaling pathways.

Induced pluripotent stem cells (iPSCs)are pluripotent stem cells obtained through transduction of specific transcription factors and reprogramming of human and animal somatic cells,Which are similar to embryonic stem cells.The iPSCs possesses characteristics of unlimited proliferation,self-reneWal and multi-differentiation.This arti-cle mainly summarized current research condition,application value and prospects of iPSCs in cardiovascular area, and its defect in application of current stage.

Objective:To study the effects of perculaneous balloon mitral valvuloplasly on mitral stenosis of patients wish rheumatic hears disease.Methods:123 patients of rheumatic mitral stenosis healed by percusaneouse balloon mitralvalvuloplasty.Left aerial pressure,mitral pressure of gradient and the area of valve orific were recorded before and after PBMV.Results:Left aerial pressure,mitral pressure of gradient decreased after PBMV and the area of valve orific increased after PBMV.Conclusion:PBMV can improve cardiac function on mitral stenosis of patients wish rheumatic hears disease.

【Objective】 The study was done to survey the transcriptional profiles of cytokines,particularly antivirus cytokines mRNA transcriptional profiles of Porcine parvovirus infection,and the host-PPV interaction.【Method】 We used PPV to infect the Porcine Kidney-15 cells,observed the PK-15 cells of inoculation PPV by microscope,measured and analyzed the viral DNA using real-time PCR.We also detected the transcript levels of cytokines MIP-1α,TGF-β1,PGK1 and MURR1 by real-time PCR.【Result】 PPV can induce cytopathic effect in PK-15 cells.The cells can be detected with PPV on 1 h postinoculation(p.i.),and the relative content of PPV DNA achieved 1 800 on 48 h p.i..We found that the transcript levels of MIP-1α and PGK1 increased obviously on 2 h p.i.,then decreased,the transcript level of TGF-β1 increased obviously on 72 h p.i.,the transcript level of MURR1 increased obviously on 24 h p.i.,then decreased after 48 h p.i..【Conclusion】 The levels of antiviral cytokines increased when PPV infected PK-15 cell.

There are conflicting data regarding the effects of transplantation of bone marrow-derived cells (BMDCs) on the severity of diabetes. We therefore inquired whether the competence of BMDCs is preserved on adoptive transfer into diabetic (db/db) mice and how the adoptive transfer of BMDCs affects vascular and metabolic abnormalities in these mice. Recipient db/db mice received infusions of BMDCs prepared from either db/db or non-diabetic heterozygout mice (db/m) mice and effects on endothelium-dependent relaxation, insulin sensitivity, and renal function were evaluated. Recipients of BMDCs from db/m, but not db/db donors showed better glucose control, exhibited striking improvement in endothelium-dependent relaxation in response to acetylcholine, and had partially restored renal function. Improved glucose control was due to enhanced insulin sensitivity, most likely secondary to improved vascular function. Enhanced apoptosis of endothelial progenitor cells under oxidative stress, as well as decreased endothelial progenitor cell numbers were responsible for the apparent functional incompetence of BMDCs from db/db donors. Treatment of db/db mice with Ebselen restored the resistance of both BMDCs and endothelial progenitor cells to oxidative stress, improved acetylcholine-induced vasorelaxation, and reduced proteinuria in db/db recipients of BMDC transplantation. In conclusion, infusion of BMDCs obtained from db/m donors to db/db recipient mice benefited macrovascular function, insulin sensitivity, and nephropathy. BMDCs obtained from db/db mice were functionally incompetent secondary to the increased proportion of apoptotic cells on oxidative stress challenge; their competence was restored by Ebselen therapy.

Objective To evaluate the efficacy and safety of combination therapy with valsartan and hydrochlorothiazide for patients with mild to myderate essential hypertension in north China.Methods One hundred and twenty-three patients were randomly divided into the V80/H12.5(valsartan 80 mg/ hydrochlorothiazide 12.5 mg) group or the V80(valsartan 80 mg) group.Six weeks after treatment,the mean decrease from baseline in sitting systolic blood pressure(SSBP) and sitting diastolic blood pressure(SDBP) were measured.The incidence of side adverse events was also observed.In addition,another 19 patients was also enrolled to accept V80/H12.5 therapy for 4 weeks.Ambulatory blood pressure monitor(ABPM) was conducted before and after drug therapy.Results Six weeks after treatment,compared with baseline,the SSBP and SDBP were significantly decreased in both the V80 group and the V80/H12.5 group.But the decrease from baseline in SSBP was significantly higher in the V80/H12.5 group than the V80 group(P0.05),and there was no difference in the change of SDBP between the two groups(P0.05).There was no significantly difference in therapeutic efficacy between the two groups(P0.05).The incidence of adverse events was also similar in the two groups(P0.05).Furthermore,the results of ABPM also showed that the systolic T/P ratio was 59.6% and the diastolic T/ P ratio was 66.4%.Conclusion Compared with nontherapy with Valsartan 80 mg,the combination therapy with V80/H12.5 can significantly decrease systolic blood pressure and also can decrease diastolic blood pressure.Furthermore,the combination with V80/H12.5 can decrease blood pressure steadily and be well tolerated.

2008年11月,河南焦作某鸡场发生一起疑似鸡传染性支气管炎的疫情.根据鸡传染性支气管炎S1基因序列设计、合成1对引物,应用RT-PCR技术对病死鸡的气管和肾脏等组织进行RT-PCR扩增,扩增出预期目的基因.结合临床症状和病理剖检变化初步诊断为鸡传染性支气管炎.

We isolated a clonal cell line (4E) from kidneys of mice expressing green fluorescent protein controlled by the endothelial-specific Tie2 promoter. When grown in a three-dimensional matrigel matrix they formed a fluorescent capillary network. In vivo angiogenesis assays using growth factor-depleted matrigel implanted plugs promoted a moderate angiogenesis of host endothelial cells. Using vascular endothelial growth factor (VEGF)-A and fibroblast growth factor-2 in the plugs containing 4E-cells resulted in a robust vasculogenesis. Transplantation of 4E cells into mice with acute renal ischemia showed selective engraftment in the ischemic kidney which promoted tubular regeneration by increasing epithelial proliferation and inhibiting apoptosis. This resulted in an accelerated functional recovery 3 days after ischemia. These mice showed a 5-fold increase in tissue VEGF expression compared to controls, but no difference in plasma VEGF level corresponding with better preservation of peritubular capillaries, perhaps due to a local paracrine effect following systemic 4E infusion. One month after ischemia, 9% of engrafted 4E cells expressed green fluorescent protein in the peritubular region while half of them expressed alpha-smooth muscle actin. Our study shows that kidney mesenchymal stem cells are capable of differentiation toward endothelial and smooth muscle cell lineages in vitro and in vivo, support new blood vessel formation in favorable conditions and promote functional recovery of an ischemic kidney.

Metabolic syndrome leads to accelerated development of macro- and microvasculopathy culminating in cardiovascular and renal complications. Using cultured endothelial cells and Zucker diabetic fat rats, we and others have demonstrated that endothelial cells undergo stress-induced premature senescence characterized by the decreased nitric oxide generation and enhanced production of peroxynitrite, in association with the increased expression of p53 and p16INK4a and accumulation of 3-nitrotyrosine-modified proteins. We reasoned that the combination of oxidative and nitrosative stress could be the cause of observed phenotypic switch in endothelial cells and employed for its prevention a selenoorganic compound, ebselen, endowed with both the antioxidant and peroxynitrite scavenging properties. Chronic therapy with ebselen resulted in the decline of the number of prematurely senescent endothelial cells and prevention of macro- and microvascular (renal) complications of metabolic syndrome. Instituting this therapy early after development of vasculopathy resulted in its amelioration. Based on these findings we propose that (a) oxidative and nitrosative stress are critical for the development of cardiovascular complications in metabolic syndrome, (b) stress-induced premature senescence of vascular endothelium represents a mechanistic link between the stressors and macro- and microvasculopathy, and (c) both can be prevented and partially reversed by antioxidant and peroxynitrite scavenging therapies.

随着人们生活水平的提高,糖尿病、冠心病、肿瘤等非传染性疾病的发病率近年来呈逐年上升趋势.糖尿病作为一种与人们生活方式密切相关的代谢性疾病正越来越广泛地影响着人类的健康.钒酸盐具有胰岛素样作用,能够增强组织对胰岛素的敏感性,改善糖尿病人的能量代谢.大量体外实验、动物模型证明,钒酸盐对1型和2型糖尿病患者均有明显降糖效果.血糖安是由我校研制开发的降糖药,其主要成分为原钒酸钠.本实验对血糖安片剂的含量测定方法进行初步探讨.

Resveratrol has been demonstrated to produce a variety of biological actions. Accumulating line of evidence supported the view that resveratrol may exert protective effect on the cardiovascular system. The aim of the study was to assess the antiarrhythmic profile as well as electrophysiological properties of resveratrol. We observe the antiarrhythmic effect of resveratrol on aconitine induced rat arrhythmia, ouabain induced guinea pig arrhythmia, and coronary ligation induced rat arrhythmia animal models. Resveratrol significantly and dose-dependently increased the doses of aconitine and ouabain required to induce the arrhythmia indexes. In coronary ligation induced rat arrhythmia model, resveratrol shortened duration of arrhythmia, decreased incidence of ventricular tachycardia and mortality. Electrophysiological experiment revealed that resveratrol could shorten APD through inhibition of ICa and selective enhancement of IKs without an effect on IKr.

Background: Mesenchymal stem cells (MSCs) can differentiate into cardiomyocytes if an appropriate cellular environment is provided. Notch signals exchanged between neighboring cells through the Notch receptor can eventually dictate cell differentiation. In our Study, we show that MSC differentiation into cardiornyocytes is dependent on the Notch signal.Methods: We created a myocardial infarction model in rat by coronary ligation, administered direct intramyocardial injection of DAPI-labeled MSC immediately, and observed the differentiation of MSCs after 14 days by irnmunofluorescence staining against troponin T. We cultured MSCs and cardiornyocytes in four ways, respectively, in vitro. (1) MSCs cocultured with cardionlyocytes obtained from neonatal rat ventricles in a ratio of 1: 10. (2) The two types of cells were cultured in two chambers separated by a semipermeable membrane as indirect coculture group. (3) Notch receptor-soluble jagged I protein was added to indirect coculture group. (4) Both jagged1 protein and gamma-secretase inhibitor-DAPT were added to indirect coculture group. Two weeks later, we observed the differentiation percentage, respectively, by immunofluorescense staining.Results: We found the differentiation of MSCs which were close to cardiornyocytes in vivo. The differentiation percentage of the four cell Culture group was 30.13 +/- 2.16% 12.52 +/- 1.18%, 26.33 +/- 2.20%, and 13.08 +/- 1.15%.Conclusions: MSCs can differentiate into cardiornyocytes in vitro and in vivo if a cardiomyocyte mcroenvironment is provided. 2. Cell-to-cell interaction is very important for the differentiation of MSCs into cardiornyocytes. 3. Jagged1 protein can activate Notch signal and enhance the differentiation or MSC into cardiomocyte, while the effect can be inhibited by DAPT. (c) 2005 Elsevier Inc. All rights reserved.

山楂Crataegus pinnalifida Bge.系蔷薇科植物,含有多种生物活性物质,如三萜酸、黄酮等.其中黄酮类成分有降压、调血脂、增加冠脉流量、强心、抗肿瘤等药理作用[1].由于山楂果实中果胶含量很高,给提取分离工作带来很大困难,因此对山楂有效成分的定量研究多集中于山楂叶和山楂核.

目的探讨心肌组织中柯萨奇病毒-腺病毒受体（CAR）表达与病毒性心肌病发病的关系。方法应用免疫组化技术检测慢性心肌炎和扩张型心肌病（DCM）心肌组织中CAR的表达;应用巢式聚合酶链反应检测相应心肌组织中柯萨奇B组病毒（CVB）RNA和腺病毒（AV）DNA,并以冠心病和先心病等非感染性心脏疾病心肌组织及意外事故死亡者正常心肌标本为对照组。结果26例心肌炎和39例DCM心肌组织中均检测到较高水平CAR表达（0.011 6±0.003 6）,而对照组仅有较低表达（0.004 0±0.0025）,两组比较差异有非常显著意义（P＜ 0.001）。心肌炎和DCM患者心肌中CVB RNA 阳性率分别为42%和35.9%（平均38.5%）,AV DNA阳性率分别为15.4%和10.3%（平均12.3%）,对照组14例均为阴性。心肌组织病毒核酸阳性者CAR免疫组化面积积分（0.013 1±0.003 4）较阴性者（0.010 1±0.003 0）明显增高（P＜ 0.001）。结论CAR在慢性心肌炎和DCM心肌组织中表达明显增高,心肌组织中CVB和AV感染与CAR表达上调相关,在慢性心肌炎和DCM的发病过程中可能起重要作用。

Objective To study the inhibitory effects and mechanism of HB on the growth of Hep 2 cell.Methods Observing HB inhibitory effect on the growth of Hep 2 cell with MTT assay. Laser scanning confocal microscope was applied to study cell intracellular calcium and the concentration of DNA in cell.Results After Hep 2 cell had been treated with HB(10μg/ml,100μg/ml )for 72h,the survival rate decreased obviously.Its DNA concentration decreased significantly after had been treated with 10 or 20μg/ml HB for 48h( P 0.001 ).On the contrary, cell intracellular calcium increased obviously( P 0.001).Conclusion HB could inhibit the growth of Hep 2 cell which is related to decreasing DNA concentration or overloading of calcium in cell.

Objective To study the extraction methods of flavonoids from hawthorn fruits. Methods Using different methods to extract flavonoids from hawthorn fruits.Results The highest extract rate(2.00%) was got through the method of continuous distillation,then seperating different parts by adsorbent resin. Comparatively high extract rate (1.96%) was got through the method of 60% ethanol ultrasonic extract, then seperating different parts by adsorbent resin. Conclusion 60% ethanol ultrasonic extract then seperating different parts by adsorbent resin is a good method to get flavonoids from hawthorn fruits.