NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
·
2020
·Vol. 394
·期 4
·765-773
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IF 2.05
Gao Jie,Yuan Guanyin,Xu Zhan,Lan Luyao,Xin Wenkuan
Bile acids are endogenous amphiphilic steroids from the metabolites of cholesterol. Studies showed that they might contribute to the pathogenesis of cardiopathy in cholestatic liver diseases. Chenodeoxycholic acid (CDCA) and deoxycholic acid (DCA) is associated with colon cancer, gallstones, and gastrointestinal disorders. However, little information is available regarding their cardiac effects. Here, we reported that CDCA (100 μM) and DCA (100 μM) significantly increased the left ventricular developed pressure of the isolated rat hearts to 122.3 ± 5.6% and 145.1 ± 13.7%, and the maximal rate of the pressure development rising and descending (± dP/dt max ) to 103.4 ± 17.6% and 124.4 ± 37.7% of the basal levels, respectively. They decreased the heart rate and prolonged the RR, QRS, and QT intervals of Langendorff-perfused hearts in a concentration-dependent manner. Moreover, CDCA and DCA increased the developed tension of left ventricular muscle and the cytosolic Ca 2+ concentrations in left ventricular myocytes; these functions positively coordinated with their inotropic effects on hearts. Additionally, CDCA (150 μM) and DCA (100 μM) decreased the sinoatrial node beating rate to 80.6 ± 3.0% and 79.7 ± 0.9% of the basal rate (334.2 ± 10.7 bpm), respectively. These results were consistent with their chronotropic effects. In conclusion, CDCA and DCA induced positive inotropic effects by elevating the Ca 2+ in left ventricular myocytes. They exerted negative chronotropic effects by lowering the pace of the sinoatrial node in rat heart. These results indicated that the potential role of bile acids in cardiopathy related to cholestasis.
研究领域:
药理学
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心血管生理学
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DOI
PubMed
高影响因子
JOURNAL OF CELLULAR PHYSIOLOGY
·
2018
·Vol. 234
·期 7
·11440-11450
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IF 3.923
Zheng-Yu Liu,Hong-Wei Pan,Yan Cao,Jiao Zheng,Yu Zhang,Yi Tang,Jin He,Yong-Jun Hu,Chang-Lu Wang,Qiong-Chao Zou,Qing-Hua Fu,Le Zhang,Jian-Qiang Peng,Jing Ling,Ning Peng,Jing-Jing Rong,Zhao-Fen Zheng
microRNAs (miRs) are essential in the development of heart failure. The aim of this study is to investigate the effect of microRNA-330 (miR-330) on left ventricular remodeling via the TGF-β1/Smad3 signaling pathway by targeting the sex-determining region Y (SRY) in mice with myocardial ischemia–reperfusion injury (MIRI). Differentially expressed gene (DEG) in myocardial ischemia–reperfusion (IR) was screened out and the miR that targeted the DEG was also predicted and verified. A model of MIRI was established to detect the expression of miR-330, SRY, transforming growth factor-β (TGF-β1), and Sekelsky mothers against dpp3 (Smad3). To further investigate the role of miR-330 in MIRI with the involvement of SRY and TGF-β1/Smad3 signaling pathway, the modeled mice were treated with different mimic, inhibitor, or small interfering RNA (siRNA) to observe the changes of the related gene expression, as well as the myocardial infarction size and volume of myocardial collagen. SRY was screened out and verified as a target gene of miR-330. The MIRI mice showed enlarged myocardial infarction size, increased volume of myocardial collagen, increased expression of miR-330, TGF-β1 and Smad3, while decreased the expression of SRY. The MIRI mice treated with miR-330 inhibitor showed decreased myocardial infarction size, the volume of myocardial collagen, and expression of TGF-β1 and Smad3 but promoted expression of SRY. Our findings demonstrated that downregulated miR-330 could suppress left ventricular remodeling to inhibit the activation of the TGF-β1/Smad3 signaling pathway via negatively targeting of SRY in mice with MIRI. This can be a potential target in the strategy to attenuate patient suffering.
研究领域:
心脏病学
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分子生物学
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遗传学
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DOI
PubMed
高影响因子
LANGMUIR
·
2024
·
IF 3.7
Chuangxin Huang,Xin Liu,Lingwei Meng,Hongyi Qu,Qi chen,Qiuliang Wang
Infections and thrombosis remain unsolved problems for implanted cardiovascular devices, such as left ventricular assist devices. Hence, the development of surfaces with improved blood compatibility and antimicrobial properties is imperative to reduce complications after artificial heart implantation. In this work, we report a novel approach to fabricate multifunctional surfaces for left ventricular transplanted ventricular assist devices (LVADs) by immobilizing nitric oxide (NO) generation catalysts and heparin and reducing silver nanoparticles in situ. The general view, structure, and chemical compositions of the pure/modified surfaces were characterized using digital imaging, scanning electron microscope (SEM), atomic force microscope (AFM), water contact angle (WCA), X-ray photoelectron spectroscopy (XPS), and inductively coupled plasma (ICP). All of the results demonstrated that the AgNPs and heparin were successfully immobilized on the surface. The Cu ions and NO release experimental results showed that the immobilized copper ions could catalyze the production of NO from S-nitrosothiols within the biological system. Meanwhile, due to the synergistic anticoagulant effect of NO and surface-immobilized heparin, the fabricated modified surfaces exhibited antiplatelet adhesion activities and good hemocompatibility. Finally, the antimicrobial activity of the samples was evaluated by Escherichia coli and Staphylococcus aureus, and cytocompatibility was measured using human umbilical vein endothelial cells (HUVECs). The results demonstrated that silver nanoparticles (AgNPs) immobilized by surface reduction reaction did not cause any significant inhibition of cell proliferation while providing stable and effective antimicrobial properties. We envision that this simple surface modification strategy with bifunctional activities of antimicrobial and anticoagulant will find widespread use in clinically used indwelling left ventricular assist devices.
研究领域:
生物医学工程
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材料科学
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心血管医学
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DOI
PubMed
高影响因子
BMC Cardiovascular Disorders
·
2024
·Vol. 24
·期 1
·1-13
·
IF 2
Wang Xin,Sun Limin
MI (myocardial infarction) often triggers severe heart failure and is one of the leading causes of death worldwide. Receptor expression-enhancing protein 5 (REEP5), a member of REEPs, acts as regulators of endoplasmic reticulum (ER) affecting cardiac functions. Based on GSE114695 profile data, REEP5 was decreased in the left ventricle of MI mice. However, its role and potential mechanism in MI remain to be investigated. In the present study, the mouse MI model was established by ligation of the left anterior descending artery. REEP5 expression was downregulated in the infarct penumbra area of MI mice. Next, its role during MI was explored by gain-of-function. Interestingly, REEP5 overexpression improved left ventricular function of mice with MI, accompanied with reduced infarct size. In cardiomyocytes, REEP5 overexpression inhibited ER stress, accompanied with repressive phosphorylation of PERK and IRE1α, and the decreased nuclear translocation of ATF6. Subsequently, REEP5 overexpression downregulated the levels of Chop and cleaved caspase-12, further alleviating ER stress-induced apoptosis, which was consistent with the in vivo results. Moreover, REEP5 was found to bind to C-type lectin member 5 A (CLEC5A), a protein that triggers cardiac dysfunction. CLEC5A, whose expression was elevated in hypoxia-induced cell models, led to cardiomyocyte apoptosis. Noteworthily, REEP5 overexpression markedly abolished the effects of CLEC5A on ER stress-induced apoptosis. Taken together, REEP5 mediated the function of CLEC5A to relieve MI via inhibiting ER stress-induced apoptosis in vivo and in vitro. REEP5 may be a promising target for treating MI.
研究领域:
心脏病学
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分子生物学
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细胞生物学
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病理学
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产品关联
DOI
PubMed
高影响因子
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
·
2021
·
IF 4.013
Weihua Wu,Qian Chai,Ziying Zhang
Recent studies have shown that blood glucose fluctuation is associated with complications of diabetes mellitus (DM). SGLT1 (sodium-dependent glucose cotransporter 1), is highly expressed in pathological conditions of heart, and is expressed in cardiomyocytes induced by high glucose. Herein, we constructed a diabetic mouse model with glucose fluctuation to investigate whether SGLT1 is involved in glucose fluctuation-induced cardiac injury. Echocardiography, histology examination, and TUNEL staining were performed to evaluate cardiac dysfunction and damage. To assess glucose fluctuation-induced oxidative stress , reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) levels were measured. To assess mitochondrial dysfunction, mitochondrial membrane potential (MMP), ATP content, mitochondrial respiratory chain complex activity, and expression of mitochondrial fusion and fission proteins were determined. The results indicated that diabetic mice with glucose fluctuation showed elevation of cardiac SGLT1 expression, left ventricular dysfunction , oxidative stress and mitochondrial dysfunction. Knockdown of SGLT1 could abrogate the effects of glucose fluctuation on cardiac injury. Thus, our study highlighted that SGLT1 plays an important role in glucose fluctuation induced cardiac injury through oxidative stress and mitochondrial dysfunction.
研究领域:
糖尿病
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心脏病学
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分子生物学
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病理生理学
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2023
·
IF 5.6
Yang Yang,Cuiting Lin,Qiang Zheng,Leqi Zhang,Yongmei Li,Qinghua Huang,Ting Wu,Zean Zhao,Lu Li,Jian Luo,Yanqing Jiang,Qun Zhang,Xing Wang,Chenglai Xia,Jianxin Pang
Hyperuricemia (HUA) is associated with left ventricular remodeling (LVR) and thereby causes the initiation and development of a large number of cardiovascular diseases. LVR is typically accompanied by cardiomyocyte energy metabolic disorder. The energy supply of cardiomyocytes is provided by glucose and fatty acid (FA) metabolism. Currently, the effect of HUA on cardiomyocytic FA metabolism is unclear. In this study, we demonstrate that UA-induced cardiomyocyte injury is associated with cytoplasmic lipid deposition, which can be ameliorated by the FA metabolism-promoting drug L-carnitine (LC). UA suppresses carnitine palmitoyl transferase 1B (CPT1B), thereby inhibiting FA transport into the mitochondrial inner matrix for elimination. LC intervention can ameliorate HUA-associated left ventricular anterior wall thickening in mice. This study showed that FA transport dysfunction plays is a critical mechanism in both cardiomyocytic injury and HUA-associated LVR and promoting cytoplasmic FA transportation through pharmacological treatment by LC is a valid strategy to attenuate HUA-associated LVR.
研究领域:
心脏病学
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代谢紊乱
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药理学
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产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2025
·
IF 5.6
Lei Wang,Yufeng Bai,Dan Ma,Wenxiu Liu,Zhiyu Shi,Chunnan Liu,Meng Zhao,Huiying Wang,Liying Luo,Jinyu Chi
Hypertension is a risk factor for cardiovascular diseases, primarily through its induction of pathological vascular and ventricular remodeling. TEA domain transcription factor 3 (TEAD3) is a transcription factor highly expressed in myocardial tissues. PDZ domain-containing 1 (PDZK1) has been reported to protect blood vessels. This study discovered decreased expression of TEAD3 and PDZK1 in the aortic tissues of spontaneously hypertensive rats (SHRs). TEAD3 overexpression in SHR vascular smooth muscle cells (VSMCs) driven by the SM22α promoter was achieved through adeno-associated virus delivery. TEAD3 overexpression alleviated aortic remodeling by reducing elastic fiber and collagen deposition. This improvement in vascular structure attenuated hypertension. Subsequently, ventricular remodeling was alleviated by reducing periaortic myocardial fibrosis and left ventricular posterior wall thickness. To elucidate the underlying mechanisms, we overexpressed TEAD3 or PDZK1 in SHR-derived VSMCs via adenoviral infection. Both interventions suppressed VSMC proliferation and migration. Crucially, TEAD3 overexpression upregulated PDZK1 expression, and DNA pull-down assays confirmed direct binding of TEAD3 protein to the PDZK1 promoter. PDZK1 knockdown abolished the anti-proliferative and anti-migratory effects of TEAD3. Further analysis suggested that PDZK1 exerted its protective role by inhibiting the phosphoinositide-3-kinase adaptor protein 1-mediated PI3K/Akt pathway. In conclusion, this study reveals that TEAD3-PDZK1 axis attenuates the abnormal proliferation and migration of VSMCs, which ameliorates aortic and left ventricular remodeling in hypertensive conditions. These findings establish a molecular basis for developing targeted therapies against hypertension-induced cardiovascular remodeling.
研究领域:
心血管研究
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分子生物学
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高血压
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转录调控
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血管生物学
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DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Luoyao Lin,Zongyi Li,Junhua Ke,Tianzi Chen,Zixuan Dong,Xiaoling Fu,Yingjun Wang
Following myocardial infarction (MI), the apoptosis of cardiomyocytes leads to the replacement of orderly myocardial tissue with scar tissue, which can result in arrhythmias and impaired cardiac function, posing serious health risks. Cardiac patches containing bioactive components offer the potential for improvement of cardiac function and attenuation of disease progression, representing a promising therapeutic approach for MI. In this study, adipose-derived active nanoparticles (ADANs) are prepared from natural adipose tissue. ADANs are spherical nanoparticles, rich in adipokines. In vitro experiments demonstrate that ADANs significantly alleviate oxidative stress damage, reducing the proportion of apoptotic cells by 51.64%. Moreover, ADANs exhibit anti-inflammatory properties. Furthermore, by integrating ADANs with a conductive hydrogel and employing 3D printing techniques, a novel biomimetic cardiac patch (Bio-GPP@A) is developed. The Bio-GPP@A exhibits structural, mechanical, and electrical anisotropy similar to natural myocardial tissue. Further in vivo experiments show that Bio-GPP@A significantly mitigates myocardial damage following MI by reducing reactive oxygen species (ROS) levels at the infarction site, inhibiting apoptosis, promoting angiogenesis, effectively suppressing left ventricular remodeling, and restoring cardiac function. In conclusion, this study introduces a novel adipose tissue derived ADANs and develops a biomimetic cardiac patch, Bio-GPP@A, offering a promising therapeutic strategy for MI repair.
研究领域:
心脏病学
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纳米技术
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生物材料
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组织工程
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再生医学
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生物医学工程
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产品关联
DOI
高影响因子
Acta Biomaterialia
·
2022
·
IF 10.633
Yuwen Lu,Tanchen Ren,Hua Zhang,Qiao Jin,Liyin Shen,Mengqi Shan,Xinzhe Zhao,Qichao Chen,Haoli Dai,Lin Yao,Jieqi Xie,Di Ye,Tengxiang Lin,Xiaoqian Hong,Kaicheng Deng,Ting Shen,Jiazhen Pan,Mengyan Jia,Jun Ling,Peng Li,Yue Zhang,Huanan Wang,Lenan Zhuang,Changyou Gao,Jifu Mao,Yang Zhu
Weak tissue adhesion remains a major challenge in clinical translation of microneedle patches. Mimicking the structural features of honeybee stingers, stiff polymeric microneedles with unidirectionally backward-facing barbs were fabricated and embedded into various elastomer films to produce self-interlocking microneedle patches. The spirality of the barbing pattern was adjusted to increase interlocking efficiency. In addition, the micro-bleeding caused by microneedle puncturing adhered the porous surface of the patch substrate to the target tissue via coagulation. In the demonstrative application of myocardial infarction treatment, the bioinspired microneedle patches firmly fixed on challenging beating hearts, significantly reduced cardiac wall stress and strain in the infarct, and maintained left ventricular function and morphology. In addition, the microneedle patch was minimally invasively implanted onto beating porcine heart in 10 minutes, free of sutures and adhesives. Therefore, the honeybee stinger-inspired microneedles could provide an adaptive and convenient means to implant patches for various medical applications. Statement of significance Adhesion between tissue and microneedle patches with smooth microneedles is usually weak. We introduce a novel barbing method of fabricating unidirectionally backward facing barbs with controllable spirality on the microneedles on microneedle patches. The microneedle patches self-interlock on mechanically dynamic beating hearts, similar to honeybee stingers. The micro-bleeding and coagulation on the porous surface provide additional adhesion force. The microneedle patches attenuate left ventricular remodeling via mechanical support and are compatible with minimally invasive implantation.
研究领域:
生物医学工程
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组织工程
·
心脏病学
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材料科学
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产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2025
·
IF 12.9
Zixuan Dong,Song Liu,Xiaobing Liu,Dong He,Qi Chu,Linjie Zhong,Xiangyu Yu,Xiaoling Fu
Diabetes is closely associated with the onset and prognosis of myocardial infarction (MI). However, current treatment strategies primarily focus on addressing MI, often neglecting the detrimental effects of hyperglycemia, a hallmark of diabetes. Hyperglycemia disrupts the crucial transition of macrophages from the M1 to M2 phenotype, thereby exacerbating MI-induced tissue damage and impeding myocardial repair. Mitochondria have emerged as key regulators of macrophage phenotype, suggesting the potential for modulating macrophages through mitochondria transfer. In this study, we developed microvesicles containing active mitochondria (Mito@euMVs), derived from enucleated mesenchymal stem cells. We found that 86.3% of the Mito@euMVs contained mitochondria, with no nuclear material present. Mito@euMVs effectively delivered mitochondria into macrophages, facilitating their transit from M1 to M2 phenotype, even in hyperglycemia. Further in vivo study using a diabetic rat model of MI confirmed their cardiac repair properties. Treatment of Mito@euMVs led to 24.55±4.33% improvement in ejection fraction and 15.48±4.04% in fractional shortening 28 days post-MI in diabetic rats. Additionally, Mito@euMVs mitigated infarcted left ventricular wall thinning and fibrosis, enhanced M2 macrophage phenotype, promoted cardiomyocyte survival. Our study emphasizes the effective modulation of macrophage phenotype via mitochondrial transfer with Mito@euMVs and highlights their promising potential in treating MI.
研究领域:
心脏病学
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糖尿病研究
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再生医学
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细胞生物学
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免疫学
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干细胞治疗
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分子生物学
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生物医学研究
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF DIABETES AND ITS COMPLICATIONS
·
2019
·
IF 2.684
Yongming Pan,Yili Rong,Junjie Huang,Keyan Zhu,Jiaojiao Chen,Chen Yu,Minli Chen
Aims A long-term high-fat/cholesterol (HFC) diet leads to hepatic insulin resistance (IR), which is associated with autonomic dysfunction and cardiovascular diseases risk increasing. However, whether this occurs in Tibetan minipigs remains unknown. We tested that a long-term HFC diet caused hepatic IR and promote cardiovascular disorders in Tibetan minipigs, and are associated with the reduction of cardiovagal tone and baroreflex sensitivity (BRS). Methods Male Tibetan minipigs were fed either a standard diet or a HFC diet, and were euthanized at 12 weeks. Thereafter, the minipigs were tested for biochemical blood indices, glucose tolerance , blood pressure, heart rate variability (HRV), BRS, and insulin receptor substrate (IRS)-associated gene and protein expression levels, as well as cardiac function. Results HFC-fed minipigs developed IR by increasing body weight, total cholesterol , fasting blood glucose and insulin levels, and nonesterified fatty acid (NEFA) and high sensitive C-reactive protein (hs-CRP) levels, glucose intolerance . Increased adipose cell size , hepatic fat deposition , malondialdehyde (MDA) content and NEFA level, down-regulation of IRS1 , IRS2 , PI3K, Akt, p-Akt, Glut2 and PGC1ɑ expression concomitant with up-regulation of mTOR , GSK3β, TNF-ɑ, FOXO1 , p-mTOR and p-p70S6K expression in the liver tissue, as well as hypertension and left ventricular diastolic dysfunction were observed in HFC-fed minipigs. HRV parameters and BRS values were further significantly reduced. Furthermore, multiple linear regression analysis showed that the development of hepatic IR toward cardiovascular disease was associated with low HFnu, RMSSD, BRS and LV −dp/dtmax, high NEFA, high hepatic TG content. Conclusion These data suggest that HFC-fed Tibetan minipigs develop hepatic IR and promote cardiovascular disorders, and are associated with lower cardiovagal tone and BRS.
研究领域:
内分泌学
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心脏病学
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营养学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
·
2021
·
IF 4.384
Lulu An,Jimusi Wuri,Zhitong Zheng,Wenqui Li,Tao Yan
Chemotherapy has several adverse effects to patients, some of which are life-threatening. We hypothesized that Doxorubicin induced microbiome imbalance and intestinal damage may contribute to Doxorubicin induced cardiac dysfunction. Male adult (2–3 months) C57BL/6 mice were administered 3 mg/kg, 5 mg/kg, 7.5 mg/kg,15 mg/kg, 20 mg/kg doses of Doxorubicin. Echocardiography was performed at 7 and 14 days after Doxorubicin administration. 16S rRNA amplicon sequencing was used to characterize microbiome changes. Fecal microbiota transplantation (FMT) was performed to evaluate the role of the microbiota on Doxorubicin induced cardiac dysfunction. Doxorubicin dose dependently increases mortality rate and induces cardiac dysfunction. 5 mg/kg-Doxorubicin significantly induces decreased left ventricular ejection fraction (LVEF) and fraction shortening (FS) as well as increased cardiac fibrosis , inflammation and oxidative stress respond without increasing mortality. 5 mg/kg-Doxorubicin induces significant decreased colorectum length, increased loss of goblet cells, numbers of ulcers and infiltration of lymphocyte clusters and decreased tight junction protein ZO-1, as well as increased plasma endotoxin level measured by ELISA assay. 16S rRNA microbiota analysis shows that Doxorubicin-induced microbiota dysbiosis with decreased community richness compared with normal control mice. FMT to Doxorubicin-5 mg treated mice significantly improved cardiac function by increasing LVEF and FS as well as decreased perivascular and interstitial fibrosis ; increased colorectum length, decreased the loss of goblet cells,infiltration of lymphocyte clusters,the number of ulcers and plasma endotoxin level; improved microbiota composition, function and diversity with increased abundance of Alloprevotella, Prevotellaceae_UCG−001 and Rikenellaceae_RC9_gut_group. We find that normal fecal transplantation improves cardiac function, decreases gut damage and alter microbiota composition induced by Doxorubicin. The microbiota appears to contribute to heart-gut interaction.
研究领域:
药理学
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心脏病学
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微生物学
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免疫学
✓ 已验证
DOI
PubMed
高影响因子
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