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Pubblicazioni recenti - diabetic cardiomyopathy
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Microvascular Disease and Small-Vessel Disease: The Nexus of Multiple Diseases of Women.
J Womens Health (Larchmt)2020 Feb;():. doi: 10.1089/jwh.2019.7826.
Patel Hena, Aggarwal Neelum T, Rao Anupama, Bryant Elizabeth, Sanghani Rupa M, Byrnes Mary, Kalra Dinesh, Dairaghi Leigh, Braun Lynne, Gabriel Sherine, Volgman Annabelle Santos,
Abstract
Microvascular disease, or small-vessel disease, is a multisystem disorder with a common pathophysiological basis that differentially affects various organs in some patients. The prevalence of small-vessel disease in the heart has been found to be higher in women compared with men. Additionally, other diseases prominently affecting women, including heart failure with preserved ejection fraction, Takotsubo cardiomyopathy, cerebral small-vessel disease, preeclampsia, pulmonary arterial hypertension (PAH), endothelial dysfunction in diabetes, diabetic cardiomyopathy, rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis, may have a common etiologic linkage related to microvascular disease. To the best of our knowledge this is the first article to investigate this potential linkage. We sought to identify various diseases with a shared pathophysiology involving microvascular/endothelial dysfunction that primarily affect women, and their potential implications for disease management. Advanced imaging technologies, such as magnetic resonance imaging and positron-emission tomography, enable the detection and increased understanding of microvascular dysfunction in various diseases. Therapies that improve endothelial function, such as those used in PAH, may also be associated with benefits across the full spectrum of microvascular dysfunction. A shared pathology across multiple organ systems highlights the need for a collaborative, multidisciplinary approach among medical subspecialty practitioners who care for women with small-vessel disease. Such an approach may lead to accelerated research in diseases that affect women and their quality of life.
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Akap1 deficiency exacerbates diabetic cardiomyopathy in mice by NDUFS1-mediated mitochondrial dysfunction and apoptosis.
Diabetologia2020 Feb;():. doi: 10.1007/s00125-020-05103-w.
Qi Bingchao, He Linjie, Zhao Ya, Zhang Ling, He Yuanfang, Li Jun, Li Congye, Zhang Bo, Huang Qichao, Xing Jinliang, Li Fei, Li Yan, Ji Lele,
Abstract
AIMS/HYPOTHESIS:
Diabetic cardiomyopathy, characterised by increased oxidative damage and mitochondrial dysfunction, contributes to the increased risk of heart failure in individuals with diabetes. Considering that A-kinase anchoring protein 121 (AKAP1) is localised in the mitochondrial outer membrane and plays key roles in the regulation of mitochondrial function, this study aimed to investigate the role of AKAP1 in diabetic cardiomyopathy and explore its underlying mechanisms.
METHODS:
Loss- and gain-of-function approaches were used to investigate the role of AKAP1 in diabetic cardiomyopathy. Streptozotocin (STZ) was injected into Akap1-knockout (Akap1-KO) mice and their wild-type (WT) littermates to induce diabetes. In addition, primary neonatal cardiomyocytes treated with high glucose were used as a cell model of diabetes. Cardiac function was assessed with echocardiography. Akap1 overexpression was conducted by injecting adeno-associated virus 9 carrying Akap1 (AAV9-Akap1). LC-MS/MS analysis and functional experiments were used to explore underlying molecular mechanisms.
RESULTS:
AKAP1 was downregulated in the hearts of STZ-induced diabetic mouse models. Akap1-KO significantly aggravated cardiac dysfunction in the STZ-treated diabetic mice when compared with WT diabetic littermates, as evidenced by the left ventricular ejection fraction (LVEF; STZ-treated WT mice [WT/STZ] vs STZ-treated Akap1-KO mice [KO/STZ], 51.6% vs 41.6%). Mechanistically, Akap1 deficiency impaired mitochondrial respiratory function characterised by reduced ATP production. Additionally, Akap1 deficiency increased cardiomyocyte apoptosis via enhanced mitochondrial reactive oxygen species (ROS) production. Furthermore, immunoprecipitation and mass spectrometry analysis indicated that AKAP1 interacted with the NADH-ubiquinone oxidoreductase 75 kDa subunit (NDUFS1). Specifically, Akap1 deficiency inhibited complex I activity by preventing translocation of NDUFS1 from the cytosol to mitochondria. Akap1 deficiency was also related to decreased ATP production and enhanced mitochondrial ROS-related apoptosis. In contrast, restoration of AKAP1 expression in the hearts of STZ-treated diabetic mice promoted translocation of NDUFS1 to mitochondria and alleviated diabetic cardiomyopathy in the LVEF (WT/STZ injected with adeno-associated virus carrying gfp [AAV9-gfp] vs WT/STZ AAV9-Akap1, 52.4% vs 59.6%; KO/STZ AAV9-gfp vs KO/STZ AAV9-Akap1, 42.2% vs 57.6%).
CONCLUSIONS/INTERPRETATION:
Our study provides the first evidence that Akap1 deficiency exacerbates diabetic cardiomyopathy by impeding mitochondrial translocation of NDUFS1 to induce mitochondrial dysfunction and cardiomyocyte apoptosis. Our findings suggest that Akap1 upregulation has therapeutic potential for myocardial injury in individuals with diabetes.
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LncRNA MALAT1 regulates diabetic cardiac fibroblasts through the Hippo/YAP signaling pathway.
Biochem Cell Biol2020 Feb;():. doi: 10.1139/bcb-2019-0434.
Liu Jiangwen, Xu Liang, Zhan XiaoRong,
Abstract
Diabetic cardiomyopathy (DCM) is a major diabetes-related microvascular disease. LncRNA MALAT1 is widely expressed in cardiomyocytes responding to hypoxia and high glucose. In this study, cardiac fibroblasts (CFs) were transfected with si-MALAT1 and exposed to high glucose. CFs in high glucose groups were treated with 30 mmoL/L glucose and control CFs were treated with 5.5 mmoL/L glucose. MALAT1 expression in the nucleus and cytoplasm of CFs was detected. CF biological behaviors and collagen production, Hippo/YAP pathway and YAP nuclear localization were measured. DCM mouse models were established to observe pathological changes of myocardium and determine levels of collagen I, Bax and Bcl-2. The interaction between MALAT1 and YAP was analyzed and CREB expression in high-glucose CFs was detected. MALAT1 was upregulated in high-glucose CFs and located in the nucleus. High-glucose increased collagen production, inflammation, cell proliferation and invasion, MST1 and LATS1 phosphorylation and promoted YAP nuclear translocation. These trends in high-glucose CFs and DCM mice were reversed by si-MALAT1. MALAT1 positively regulated YAP nuclear translocation by binding to CREB. CREB was increased in high-glucose CFs but decreased after silencing MALAT1. Taken together, si-MALAT1 reduces inflammation and collagen accumulation in high-glucose CFs and DCM mice via the Hippo/YAP pathway and CREB.
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Melatonin alleviates cardiac fibrosis via inhibiting lncRNA MALAT1/miR-141-mediated NLRP3 inflammasome and TGF-?1/Smads signaling in diabetic cardiomyopathy.
FASEB J2020 Feb;():. doi: 10.1096/fj.201902692R.
Che Hui, Wang Yueqiu, Li Hui, Li Yang, Sahil Abbas, Lv Jie, Liu Yining, Yang Zhenyu, Dong Ruixue, Xue Hongru, Wang Lihong,
Abstract
Melatonin is a hormone produced by the pineal gland, and it has extensive beneficial effects on various tissue and organs; however, whether melatonin has any effect on cardiac fibrosis in the pathogenesis of diabetic cardiomyopathy (DCM) is still unknown. Herein, we found that melatonin administration significantly ameliorated cardiac dysfunction and reduced collagen production by inhibiting TGF-?1/Smads signaling and NLRP3 inflammasome activation, as manifested by downregulating the expression of TGF-?1, p-Smad2, p-Smad3, NLRP3, ASC, cleaved caspase-1, mature IL-1?, and IL-18 in the heart of melatonin-treated mice with diabetes mellitus (DM). Similar beneficial effects of melatonin were consistently observed in high glucose (HG)-treated cardiac fibroblasts (CFs). Moreover, we also found that lncRNA MALAT1 (lncR-MALAT1) was increased along with concomitant decrease in microRNA-141 (miR-141) in DM mice and HG-treated CFs. Furthermore, we established NLRP3 and TGF-?1 as target genes of miR-141 and lncR-MALAT1 as an endogenous sponge or ceRNA to limit the functional availability of miR-141. Finally, we observed that knockdown of miR-141 abrogated anti-fibrosis action of melatonin in HG-treated CFs. Our findings indicate that melatonin produces an antifibrotic effect via inhibiting lncR-MALAT1/miR-141-mediated NLRP3 inflammasome activation and TGF-?1/Smads signaling, and it might be considered a potential agent for the treatment of DCM.
© 2020 Federation of American Societies for Experimental Biology.
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A review on the potential of Resveratrol in prevention and therapy of diabetes and diabetic complications.
Biomed Pharmacother2020 Feb;125():109767. doi: S0753-3322(19)35389-2.
Huang Dan-Dan, Shi Guangjiang, Jiang Yaping, Yao Chao, Zhu Chuanlin,
Abstract
Diabetes mellitus (DM) is a major world health problem and one of the most studied diseases, which are highly prevalent in the whole world, it is frequently associated with severe clinical complications, such as diabetic cardiomyopathy, nephropathy, retinopathy, neuropathy etc. Scientific research is continuously casting about for new monomer molecules from Chinese herbal medicine that could be invoked as candidate drugs for fighting against diabetes and its complications. Resveratrol (RES), a polyphenol phytoalexin, possesses diverse biochemical and physiological actions, including antiplatelet, estrogenic, and anti-inflammatory properties. It is recently gaining scientific interest for RES in controlling blood sugar and fighting against diabetes and its complications properties in various types of diabetic models. These beneficial effects seem to be due to the multiple actions of RES on cellular functions, which make RES become a promising molecule for the treatment of diabetes and diabetic complications. Here, we review the mechanism of action and potential therapeutic use of RES in prevention and mitigation of these diseases in recent ten years to provide a reference for further research and development of RES.
Copyright © 2020 The Authors. Published by Elsevier Masson SAS.. All rights reserved.
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Effects of on Inflammation, Apoptosis, and Organ Toxicity in STZ-Induced Diabetic Cardiomyopathy.
Biomedicines2020 Feb;8(2):. doi: E29.
Alabi Toyin D, Chegou Novel N, Brooks Nicole L, Oguntibeju Oluwafemi O,
Abstract
Persistent hyperglycemia is known to cause enhanced generation of reactive oxygen species in diabetes. Several inflammatory cytokines are induced by oxidative stress, and their release also leads to increased oxidative stress; this makes oxidative stress one of the important factors in the development of chronic inflammation and other immune responses. These have been implicated in the development of diabetic complications such as nephropathy and cardiomyopathy. has been shown to possess antioxidant and anti-inflammatory potentials. The present study investigated the immunomodulatory potential and the antiapoptotic ability of to ameliorate heart toxicity and injury in type II diabetes. Two weeks of fructose (10%) administration followed by single intraperitoneal injection of streptozotocin (40 mg/kg) were used to induce type II diabetes in male Wistar rats. Leaf extract (aqueous) of (200 and 400 mg/kg) was administered orally for six weeks. Blood glucose concentrations and body weights before and after interventions were determined. Interleukin (IL)-1?, IL-6, IL-10, IL-18, monocyte chemoattractant protein 1 (MCP-1), and tumor necrosis factor alpha (TNF?) were measured in the heart homogenates. Catalase (CAT), superoxide dismutase (SOD), total protein, oxygen radical absorbance capacity (ORAC), ferric reducing antioxidant power (FRAP), thiobarbituric acid reactive substances (TBARS), and heart-type fatty acid-binding protein (H-FABP) levels were determined. Expressions of transcription factors (Nrf 2 and NFkB/p65) and apoptotic markers were also investigated in the heart. administration reduced pro-inflammatory cytokines, increased anti-inflammatory markers, and enhanced antioxidant defense in the heart of diabetic treated animals. is a new, promising therapeutic agent that can be explored for the treatment of pathological conditions associated with immune responses and will be a useful tool in the management of associated diabetic complications.
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Unbalance Between Sarcoplasmic Reticulum Ca Uptake and Release: A First Step Toward Ca Triggered Arrhythmias and Cardiac Damage.
Front Physiol2019 ;10():1630. doi: 10.3389/fphys.2019.01630.
Federico Marilén, Valverde Carlos A, Mattiazzi Alicia, Palomeque Julieta,
Abstract
The present review focusses on the regulation and interplay of cardiac SR Ca handling proteins involved in SR Ca uptake and release, i.e., SERCa2/PLN and RyR2. Both RyR2 and SERCA2a/PLN are highly regulated by post-translational modifications and/or different partners' proteins. These control mechanisms guarantee a precise equilibrium between SR Ca reuptake and release. The review then discusses how disruption of this balance alters SR Ca handling and may constitute a first step toward cardiac damage and malignant arrhythmias. In the last part of the review, this concept is exemplified in different cardiac diseases, like prediabetic and diabetic cardiomyopathy, digitalis intoxication and ischemia-reperfusion injury.
Copyright © 2020 Federico, Valverde, Mattiazzi and Palomeque.
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The PGC-1? -HO-1 axis, a powerful antioxidative pathway with potential to attenuate diabetic cardiomyopathy.
Antioxid Redox Signal2020 Feb;():. doi: 10.1089/ars.2019.7989.
Waldman Maayan, Arad Michael, Abraham Nader G, Hochhauser Edith,
Abstract
SIGNIFICANCE:
From studies of diabetic animal models, the downregulation of PGC-1? -HO-1 axis appears to be a crucial event in the development of obesity and diabetic cardiomyopathy (DCM). In this review, we discuss the role of metabolic, and biochemical stressors in the rodent and human pathophysiology of DCM. A crucial contributor for many cardiac pathologies is excessive production of reactive oxygen species (ROS) pathologies which lead to extensive cellular damage by impairing mitochondrial function and directly oxidizing DNA, proteins, and lipid membranes. We discuss the role of ROS production and inflammatory pathways with multiple contributing and confounding factors leading to DCM. Recent Advances: The relevant biochemical pathways critical to a therapeutic approach to treat DCM specifically caloric restriction and its relation to the PGC-1? -HO-1 axis in the attenuation of DCM are elucidated.
CRITICAL ISSUES:
The increased prevalence of Diabetes mellitus type 2 (DM2), a major contributor to unique cardiomyopathy characterized by cardiomyocyte hypertrophy with no effective clinical treatment. This review highlights the role of mitochondrial dysfunction in the development of DCM and potential oxidative targets to attenuate oxidative stress and attenuate DCM.
FUTURE DIRECTIONS:
Targeting the PGC-1? - HO-1 axis is a promising approach to ameliorate diabetic cardiomyopathy through improvement in mitochondrial function and antioxidant defenses. Pharmacological inducer to activate PGC-1? and HO-1 described in this review may be a promising therapeutic approach in the clinical setting.
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The Diabetic Cardiac Fibroblast: Mechanisms Underlying Phenotype and Function.
Int J Mol Sci2020 Feb;21(3):. doi: E970.
Levick Scott P, Widiapradja Alexander,
Abstract
Diabetic cardiomyopathy involves remodeling of the heart in response to diabetes that includes microvascular damage, cardiomyocyte hypertrophy, and cardiac fibrosis. Cardiac fibrosis is a major contributor to diastolic dysfunction that can ultimately result in heart failure with preserved ejection fraction. Cardiac fibroblasts are the final effector cell in the process of cardiac fibrosis. This review article aims to describe the cardiac fibroblast phenotype in response to high-glucose conditions that mimic the diabetic state, as well as to explain the pathways underlying this phenotype. As such, this review focuses on studies conducted on isolated cardiac fibroblasts. We also describe molecules that appear to oppose the pro-fibrotic actions of high glucose on cardiac fibroblasts. This represents a major gap in knowledge in the field that needs to be addressed.
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Use of a Systematic Pharmacological Methodology to Explore the Mechanism of Shengmai Powder in Treating Diabetic Cardiomyopathy.
Med Sci Monit2020 Feb;26():e919029. doi: 10.12659/MSM.919029.
Zhang Shi-Ying, Yang Kai-Lin, Long Zhi-Yong, Li Wei-Qing, Huang Hui-Yong,
Abstract
BACKGROUND Cardiovascular complications, such as diabetic cardiomyopathy (DCM), are the leading cause of death in diabetic patients. Shengmai Powder (SMP) was found to have cardioprotective effects. MATERIAL AND METHODS Based on the systematic pharmacological methodology, this research determined the genes of DCM and the known targets of SMP, predicted potential compounds and targets of SMP, constructed networks for DCM and SMP, and performed network analysis. RESULTS Five network were constructed: (1) the DCM gene PPI network; (2) the Compound-compound target network of SMP; (3) the SMP-DCM PPI network; (4) the Compound-known target network of SMP; (5) and the SMP known target-DCM PPI network. Several DCM and treatment related targets, clusters, signaling pathways, and biological processes were found. CONCLUSIONS SMP is able to regulate glycometabolism-related, lipid metabolism-related, inflammatory response-related, oxidative stress-related signaling pathways, and biological processes and targets, which suggests that SMP may have a therapeutic effect on DCM.
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Diabetic animal fed with high-fat diet prevents the protective effect of myocardial ischemic preconditioning effect in isolated rat heart perfusion model.
J Biochem Mol Toxicol2020 Feb;():e22457. doi: 10.1002/jbt.22457.
Ansari Mahalakshmi, Kurian Gino A,
Abstract
Diabetic heart (diabetes mellitus [DM]) has been shown to attenuate the beneficial effect of ischemic preconditioning (IPC) in rat heart. But the effect of IPC on diabetic rat heart that develops myopathy remains unclear. This study was designed to test the impact of IPC on diabetic cardiomyopathy (DCM) rat heart. Male Wistar rats were grouped as (a) normal, (b) DM (streptozotocin: 65?mg/kg; fed with normal diet), and (c) DCM (streptozotocin: 65?mg/kg; fed with high-fat diet). Isolated rat hearts from each group were randomly subjected to (a) normal perfusion, (b) ischemia-reperfusion (I/R), and (c) IPC procedure. At the end of the perfusion experiments, hearts were analyzed for injury, contractile function, mitochondrial activity, and oxidative stress. The results obtained from hemodynamics, cardiac injury markers, and caspase-3 activity showed that DCM rat displayed prominent I/R-associated cardiac abnormalities than DM rat heart. But the deteriorated physiological performance and cardiac injury were not recovered in both DM and DCM heart by IPC procedure. Unlike normal rat heart, IPC did not reverse mitochondrial dysfunction (determined by electron transport chain enzymes activity, ATP level, and membrane integrity, expression levels of genes like PGC-1?, GSK3?, complex I, II, and V) in DCM and DM rat heart. The present study demonstrated that IPC failed to protect I/R-challenged DCM rat heart, and the underlying pathology was associated with deteriorated mitochondrial function.
© 2020 Wiley Periodicals, Inc.
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Liraglutide reduces hyperglycemia-induced cardiomyocyte death through activating glucagon-like peptide 1 receptor and targeting AMPK pathway.
J Recept Signal Transduct Res2020 Apr;40(2):133-140. doi: 10.1080/10799893.2020.1719517.
Ma Guanqun, Liu Yingwu, Wang Yu, Wen Zhinan, Li Xin, Zhai Hu, Miao Li, Luo Jieying,
Abstract
Hyperglycemia-mediated cardiomyocyte damage is associated with inflammation and AMPK inactivation. The aim of our study is to explore the protective effects exerted by liraglutide on AMPK pathway and glucagon-like peptide 1 receptor in diabetic cardiomyopathy. Cardiomyocytes were treated with high-glucose stress and cardiomyocyte viability was determined (3-(4,5-dimethylthiazol-2-yl)-2,5diphenyltetrazolium bromide assay. Besides, LDH release, immunofluorescence, and qPCR were used to verify the influence of liraglutide on hyperglycemia-treated cardiomyocytes. Hyperglycemia treatment caused inflammation response and oxidative stress were significantly elevated in cardiomyocytes. This alteration could be reversed by liraglutide. Besides, cell viability was reduced whereas apoptosis was increased after exposure to high glucose treatment. However, liraglutide treatment could attenuate apoptosis and reverse cell viability in cardiomyocyte. Further, we found that AMPK pathway was also activated and glucagon-like peptide 1 receptor expression was increased in response to liraglutide treatment. Liraglutide could attenuate hyperglycemia-mediated cardiomyocyte damage through reversing AMPK pathway and upregulating glucagon-like peptide 1 receptor.
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Metoprolol and bisoprolol ameliorate hypertrophy of neonatal rat cardiomyocytes induced by high glucose via the PKC/NF-?B/c-fos signaling pathway.
Exp Ther Med2020 Feb;19(2):871-882. doi: 10.3892/etm.2019.8312.
Wang Min, Lv Qingbo, Zhao Liding, Wang Yao, Luan Yi, Li Zhengwei, Fu Guosheng, Zhang Wenbin,
Abstract
Hyperglycemia caused by diabetes mellitus could increase the risk of diabetic cardiomyopathy. However, to the best of our knowledge, the underlying mechanism of this process is still not fully explored. Thus, developing ways to prevent hyperglycemia can be beneficial for diabetic patients. The present study was designed to investigate the influence of metoprolol and bisoprolol on the cardiomyocytic hypertrophy of neonatal rat cardiomyocytes. Cardiomyocytes were cultured in two types of media: One with low glucose levels and one with high glucose levels. Cardiomyocytes cultured in high glucose were further treated with the following: A protein kinase C (PKC) inhibitor, an NF-?B inhibitor, metoprolol or bisoprolol. The pulsatile frequency, cellular diameter and surface area of cardiomyocytes were measured. Protein content and [H]-leucine incorporation were determined, atrial natriuretic peptide (ANP), ?-myosin heavy chain (?-MHC) and ?-myosin heavy chain (?-MHC) mRNA levels were calculated by reverse transcription-quantitative PCR, while the expression and activation of PKC-?, PKC-?, NF-?B, tumor necrosis factor-? (TNF-?), and c-fos were detected by western blotting. Metoprolol or bisoprolol were also used in combination with PKC inhibitor or NF-?B inhibitor to determine whether the hypertrophic response would be attenuated to a lower extent compared with metroprolol or bisoprolol alone. Cardiomyocytes cultured in high glucose presented increased pulsatile frequency, cellular diameter, surface area, and protein content and synthesis, higher expression of ANP and ?-MHC, and lower ?-MHC expression. High glucose levels also upregulated the expression and activation of PKC-?, PKC-?, NF-?B, TNF-? and c-fos. Metoprolol and bisoprolol partly reversed the above changes, while combined use of metoprolol or bisoprolol with PKC inhibitor or NF-?B inhibitor further ameliorated the hypertrophic response mentioned above to lower levels compared with using metroprolol or bisoprolol alone. In conclusion, metoprolol and bisoprolol could prevent hypertrophy of cardiomyocytes cultured in high glucose by the inhibition of the total and phospho-PKC-?, which could further influence the PKC-?/NF-?B/c-fos signaling pathway.
Copyright: © Wang et al.
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Knockout of farnesoid X receptor aggravates process of diabetic cardiomyopathy.
Diabetes Res Clin Pract2020 Jan;161():108033. doi: S0168-8227(19)31702-4.
Qiang Sujing, Tao Lingyun, Zhou Jie, Wang Qianwan, Wang Kesheng, Lu Meiling, Wang Weifeng, Han Lin, Xue Shaobo, Chen Yan, Zhu Huanhuan, Liu Zheng, Zhang Yue,
Abstract
Previous studies have shown that FXR is involved in glycolipid metabolism, tissue inflammation and regeneration in organs such as the liver, intestines and kidneys. Although FXR has been reported in cardiac tissue, its function in diabetic cardiomyopathy has not been reported. Here, we successfully constructed a diabetic mouse model of FXR and evaluated the effects of FXR knockout on cardiac function in mice by measuring various indicators. We demonstrated that blood glucose levels in diabetic mice are significantly elevated in the case of FXR knockout. Our findings from cardiac ultrasound and tissue HE staining supported that FXR knockout aggravates diabetic cardiomyopathy. Masson staining of myocardial tissue and quantitative detection of ?-SMA by qPCR suggest that FXR knockout exacerbates cardiac fibrosis in diabetic cardiomyopathy. Combined with the results of Oil Red staining and quantitative detection of triglycerides in fresh tissue blocks, we hypothesized that FXR knockout aggravates diabetes-induced cardiac lipid accumulation. Altogether our results revealed a role of the FXR in the diabetic cardiomyopathy, suggesting a possible novel target for the treatment of diabetic cardiomyopathy.
Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.
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Berberine for prevention of dementia associated with diabetes and its comorbidities: A systematic review.
J Integr Med2020 Jan;():. doi: S2095-4964(20)30005-4.
Shinjyo Noriko, Parkinson James, Bell Jimmy, Katsuno Tatsuro, Bligh Annie,
Abstract
BACKGROUND:
A growing number of epidemiological studies indicate that metabolic syndrome (MetS) and its associated features play a key role in the development of certain degenerative brain disorders, including Alzheimer's disease and vascular dementia. Produced by several different medicinal plants, berberine is a bioactive alkaloid with a wide range of pharmacological effects, including antidiabetic effects. However, it is not clear whether berberine could prevent the development of dementia in association with diabetes.
OBJECTIVE:
To give an overview of the therapeutic potential of berberine as a treatment for dementia associated with diabetes.
SEARCH STRATEGY:
Database searches A and B were conducted using PubMed and ScienceDirect. In search A, studies on berberine's antidementia activities were identified using "berberine" and "dementia" as search terms. In search B, recent studies on berberine's effects on diabetes were surveyed using "berberine" and "diabetes" as search terms.
INCLUSION CRITERIA:
Clinical and preclinical studies that investigated berberine's effects associated with MetS and cognitive dysfunction were included.
DATA EXTRACTION AND ANALYSIS:
Data from studies were extracted by one author, and checked by a second; quality assessments were performed independently by two authors.
RESULTS:
In search A, 61 articles were identified, and 22 original research articles were selected. In search B, 458 articles were identified, of which 101 were deemed relevant and selected. Three duplicates were removed, and a total of 120 articles were reviewed for this study. The results demonstrate that berberine exerts beneficial effects directly in the brain: enhancing cholinergic neurotransmission, improving cerebral blood flow, protecting neurons from inflammation, limiting hyperphosphorylation of tau and facilitating ?-amyloid peptide clearance. In addition, evidence is growing that berberine is effective against diabetes and associated disorders, such as atherosclerosis, cardiomyopathy, hypertension, hepatic steatosis, diabetic nephropathy, gut dysbiosis, retinopathy and neuropathy, suggesting indirect benefits for the prevention of dementia.
CONCLUSION:
Berberine could impede the development of dementia via multiple mechanisms: preventing brain damages and enhancing cognition directly in the brain, and indirectly through alleviating risk factors such as metabolic dysfunction, and cardiovascular, kidney and liver diseases. This study provided evidence to support the value of berberine in the prevention of dementia associated with MetS.
Copyright © 2020 Shanghai Changhai Hospital. Published by Elsevier B.V. All rights reserved.
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Tcf3-activated lncRNA Gas5 regulates newborn mouse cardiomyocyte apoptosis in diabetic cardiomyopathy.
J Cell Biochem2020 Jan;():. doi: 10.1002/jcb.29630.
Su Dongsheng, Ju Yansong, Han Wei, Yang Yanhua, Wang Fengyun, Wang Tong, Tang Jianmin,
Abstract
Diabetic cardiomyopathy can cause cardiac dysfunction and eventually lead to heart failure and sudden death. Long noncoding RNA (lncRNA) Gas5 has been reported to play a function in cardiomyocyte. Here we studied the function of Gas5 on newborn mouse cardiomyocyte (NMC) apoptosis to detect its molecular mechanism. High-glucose treatment was implemented to induce the apoptosis of NMC in this study. And terminal deoxynucleotidyl transferase dUTP nick-end labeling assay, JC-1 assay, and flow cytometry analysis were conducted to know about the apoptosis of NMC when Gas5 and Tcf3 were silenced. Meanwhile, RNA pull-down assay and luciferase reporter assay were conducted to verify the binding of RNAs. Finally, rescue assay was implemented to evaluate the influence on apoptosis situation affected by competing endogenous RNA pathways. Tcf3 was found to bind to the Gas5 promoter to activate the expression of Gas5. Meanwhile, Gas5 and Tcf3 were both found to promote the apoptosis of NMC. Also, mmu-miR-320-3p could bind to Gas5 and Tcf3. Moreover, the Gas5/miR-320-3p/Tcf3 pathway was found to modulate the apoptosis of NMC. In conclusion, Tcf3-activated lncRNA Gas5 regulates NMC apoptosis in diabetic cardiomyopathy.
© 2020 Wiley Periodicals, Inc.
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Assessment of the Preventive Effect Against Diabetic Cardiomyopathy of FGF1-Loaded Nanoliposomes Combined With Microbubble Cavitation by Ultrasound.
Front Pharmacol2019 ;10():1535. doi: 10.3389/fphar.2019.01535.
Zheng Lei, Shen Chuan-Li, Li Jian-Min, Ma Yu-Lei, Yan Ning, Tian Xin-Qiao, Zhao Ying-Zheng,
Abstract
Acidic fibroblast growth factor (FGF1) has great potential in preventing diabetic cardiomyopathy. This study aimed to evaluate the preventive effect of FGF1-loaded nanoliposomes (FGF1-nlip) combined with ultrasound-targeted microbubble destruction (UTMD) on diabetic cardiomyopathy (DCM) using ultrasound examination. Nanoliposomes encapsulating FGF1 were prepared by reverse phase evaporation. DM model rats were established by intraperitoneal injection of streptozotocin (STZ), and different forms of FGF1 (FGF1 solution, FGF1-nlip, and FGF1-nlip+UTMD) were used for a 12-week intervention. According to the transthoracic echocardiography and velocity vector imaging (VVI) indexes, the LVEF, LVFS, and VVI indexes (Vs, Sr, SRr) in the FGF1-nlip+UTMD group were significantly higher than those in the DM model group and other FGF1 intervention groups. From the real-time myocardial contrast echocardiography (RT-MCE) indexes, the FGF1-nlip+UTMD group A and A×? showed signi?cant differences from the DM model group and other FGF1 intervention groups. Cardiac catheter hemodynamic testing, CD31 immunohistochemical staining, and electron microscopy also confirmed the same conclusion. These results confirmed that the abnormalities, including myocardial dysfunction and perfusion impairment, could be suppressed to different extents by the twice weekly FGF1 treatments for 12 consecutive weeks (free FGF1, FGF1-nlip, and FGF1-nlip+UTMD), with the strongest improvements observed in the FGF1-nlip+UTMD group. In conclusion, the VVI and RT-MCE techniques can detect left ventricular systolic function and perfusion changes in DM rats, providing a more effective experimental basis for the early detection and treatment evaluation of DCM, which is of great significance for the prevention of DCM.
Copyright © 2020 Zheng, Shen, Li, Ma, Yan, Tian and Zhao.
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Simultaneous inhibition of neprilysin and activation of ACE2 prevented diabetic cardiomyopathy.
Pharmacol Rep2019 Sep;71(5):958-967. doi: 10.1016/j.pharep.2019.05.008.
Malek Vajir, Sharma Nisha, Gaikwad Anil Bhanudas,
Abstract
BACKGROUND:
Neprilysin inhibitors (NEPi) are assisting the renin-angiotensin system (RAS) inhibitors in halting diabetic cardiomyopathy (DCM). Away from conventional tactic, a recent report revealed the renoprotective potential of NEPi and angiotensin-converting enzyme (ACE2) activator combination therapy against diabetic nephropathy. However, this combination so far not evaluated against DCM, thus the present investigation aiming the same.
METHODS:
Streptozotocin-induced (55 mg/kg, ip) type 1 diabetic (T1 D) male Wistar rats were treated with either monotherapy of thiorphan (0.1 mg/kg/day, po) or diminazene aceturate (5 mg/kg/day, po), or their combination therapy, for four weeks. After hemodynamic measurements, all the rats' heart and plasma were collected for biochemistry, ELISA, histopathology, and immunoblotting.
RESULTS:
Metabolic perturbations and failing cardiac functions associated with diabetes were markedly attenuated by combination therapy. Besides, unfavourable alterations in RAS and natriuretic peptides system (NPS) were corrected by combination therapy. Interestingly, combination therapy significantly increased plasma and heart cGMP levels compared to T1D and monotherapy receiving rats. Moreover, rats receiving combination therapy exhibited significant inhibition of activated NF-KB, TGF-p and apoptotic signalling, and a notable reduction in cardiac fibrosis when compared to Tl D rats. Expressions of posttranslational histone modifications markers; H3K4Me2 and its methyltransferases (SET7/9 and RBBP5) were significantly enhanced in T1D hearts, which were significantly reduced by combination therapy.
CONCLUSIONS:
The NEPi and ACE2 activator combination therapy effectively prevented DCM by normalising RAS and NPS activities, increasing cGMP, inhibiting inflammatory, pro-fibrotic and apoptotic signalling, and reversing H3K4Me2 and its methyl transferases expressions.
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Salvianolic acid B improves myocardial function in diabetic cardiomyopathy by suppressing IGFBP3.
J Mol Cell Cardiol2020 Jan;139():98-112. doi: S0022-2828(20)30021-3.
Li Chang-Ling, Liu Bin, Wang Zhao-Yang, Xie Fei, Qiao Wen, Cheng Jie, Kuang Jiang-Ying, Wang Ying, Zhang Ming-Xiang, Liu De-Shan,
Abstract
BACKGROUND:
Salvianolic acid B (Sal B) is the representative component of phenolic acids derived from the dried root and rhizome of Salvia miltiorrhiza Bge. (Labiatae), which has been widely used for the treatment of cardiovascular and cerebrovascular diseases. However, the effect of Sal B on diabetic cardiomyopathy (DCM) is still unclear.
METHODS:
Type 1 diabetes mellitus was induced in C57BL/6 J mice by streptozotocin (STZ) treatment, whereas meanwhile Salvianolic Acid B (Sal B (15 or 30 mg/kg/d) was intraperitoneally injected for 16 weeks. At the end of this period, cardiac function was assessed by echocardiography, and total collagen deposition was evaluated by Masson's trichrome and Picrosirius Red staining. Human umbilical vein endothelial cells exposed to hypoxia were used to investigate the effect of different doses of Sal B on angiogenesis and tube formation in vitro. Transcriptome sequencing was performed to identify potential targets of Sal B.
RESULTS:
Sal B ameliorated left ventricular dysfunction and remodeling, and decreased collagen deposition in the heart of diabetic mice. Administration of Sal B increased the expression of vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2) and VEGFA in a dose-dependent manner and promoted angiogenesis both in vivo and in vitro. Furthermore, Sal B reduced HG-induced insulin-like growth factor-binding protein 3 (IGFBP3) expression, induced the phosphorylation of extracellular signal-regulated protein kinase and protein kinase B (AKT) activities, enhanced cell proliferation, and activated VEGFR2/VEGFA signaling in endothelial cells. The underlying mechanisms involve SalB that enhances IGFBP3 promoter DNA methylation and induce nuclear translocation of IGFBP3 in HUVECs under hypoxia.
CONCLUSIONS:
Sal B promoted angiogenesis and alleviated cardiac fibrosis and cardiac remodeling in DCM by suppressing IGFBP3.
Copyright © 2020 Elsevier Ltd. All rights reserved.
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The Role of Bone Morphogenetic Protein 7 (BMP-7) in Inflammation in Heart Diseases.
Cells2020 Jan;9(2):. doi: E280.
Aluganti Narasimhulu Chandrakala, Singla Dinender K,
Abstract
Bone morphogenetic protein-7 is (BMP-7) is a potent anti-inflammatory growth factor belonging to the Transforming Growth Factor Beta (TGF-?) superfamily. It plays an important role in various biological processes, including embryogenesis, hematopoiesis, neurogenesis and skeletal morphogenesis. BMP-7 stimulates the target cells by binding to specific membrane-bound receptor BMPR 2 and transduces signals through mothers against decapentaplegic (Smads) and mitogen activated protein kinase (MAPK) pathways. To date, rhBMP-7 has been used clinically to induce the differentiation of mesenchymal stem cells bordering the bone fracture site into chondrocytes, osteoclasts, the formation of new bone via calcium deposition and to stimulate the repair of bone fracture. However, its use in cardiovascular diseases, such as atherosclerosis, myocardial infarction, and diabetic cardiomyopathy is currently being explored. More importantly, these cardiovascular diseases are associated with inflammation and infiltrated monocytes where BMP-7 has been demonstrated to be a key player in the differentiation of pro-inflammatory monocytes, or M1 macrophages, into anti-inflammatory M2 macrophages, which reduces developed cardiac dysfunction. Therefore, this review focuses on the molecular mechanisms of BMP-7 treatment in cardiovascular disease and its role as an anti-fibrotic, anti-apoptotic and anti-inflammatory growth factor, which emphasizes its potential therapeutic significance in heart diseases.
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