scholarly journals Ultrasound-targeted Microbubble Destruction Promotes Myocardial Angiogenesis and Functional Improventments in Rat Model of Diabetic Cardiomyopathy

2020 ◽  
Author(s):  
Xijun Zhang ◽  
Haohui Zhu ◽  
Nanqian Zhou ◽  
Zhixin Fang ◽  
Yuping Yang ◽  
...  
Keyword(s):  
Protective Effect ◽  
Diabetic Cardiomyopathy ◽  
Rat Model ◽  
Critical Role ◽  
Therapeutic Angiogenesis ◽  
Diabetic Patients ◽  
Therapeutic Effects ◽  
Novel Approach ◽  
Cardiac Functions ◽  
Cycle Group

Abstract Objective: Microvascular insufficiency takes a critical role in the development of diabetic cardiomyopathy (DCM), therapeutic angiogenesis has been mainly used for the treatment of ischemic diseases. The present study sought to investigate the preclinical performance of SonoVue microbubbles(MBs) combined ultrasound(US) treatment on myocardial angiogenesis in a rat model of DCM and investigate the optimal ultrasonic parameters.Methods and Results: After the DCM model was established, the cardio protective effect of SonoVue MBs using US techniques was examined by histology, morphometry, and echocardiography evaluations. From morphologic observation and echocardiography, the DCM rats had a set of structural abnormalities in the heart compared to the normal rats. The US-MB groups exerted cardio protective effect in DCM rats, improved reparative neovascularization and increased cardiac perfusion, while the 26 cycle group showed significantly therapeutic effects on the cardiac functions in DCM rats.Conclusion: This strategy using SonoVue MB and US can significantly improve or even reverse cardiac dysfunction and pathological abnormalities, especially using the 26 cycle parameters. Under further study, this combined strategy might provide a novel approach for early intervention of DCM in diabetic patients.

scholarly journals Ultrasound-targeted microbubble destruction promotes myocardial angiogenesis and functional improvements in rat model of diabetic cardiomyopathy

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xijun Zhang ◽  
Xinqiao Tian ◽  
Peng Li ◽  
Haohui Zhu ◽  
Nanqian Zhou ◽  
...  
Keyword(s):  
Diabetic Cardiomyopathy ◽  
Rat Model ◽  
Therapeutic Angiogenesis ◽  
Diabetic Patients ◽  
Therapeutic Effects ◽  
Sprague Dawley ◽  
Novel Approach ◽  
Cardiac Functions ◽  
The Us ◽  
Cycle Group

Abstract Background Microvascular insufficiency plays an important role in the development of diabetic cardiomyopathy (DCM), therapeutic angiogenesis has been mainly used for the treatment of ischemic diseases. This study sought to verify the preclinical performance of SonoVue microbubbles (MB) combined ultrasound (US) treatment on myocardial angiogenesis in the rat model of DCM and investigate the optimal ultrasonic parameters. Methods The male Sprague–Dawley (SD) rats were induced DCM by streptozotocin through intraperitoneal injecting and fed with high-fat diet. After the DCM model was established, the rats were divided into the normal group, DCM model group, and US + MB group, while the US + MB group was divided into four subsets according to different pulse lengths (PL) (8 cycles;18 cycle;26 cycle; 36 cycle). After all interventions, all rats underwent conventional echocardiography to examine the cardiac function. The rats were sacrificed and myocardial tissue was examined by histology and morphometry evaluations to detect the myocardial protective effect of SonoVue MBs using US techniques. Results From morphologic observation and echocardiography, the DCM rats had a series of structural abnormalities of cardiac myocardium compared to the normal rats. The US-MB groups exerted cardioprotective effect in DCM rats, improved reparative neovascularization and increased cardiac perfusion, while the 26 cycle group showed significant therapeutic effects on the cardiac functions in DCM rats. Conclusion This strategy using SonoVue MB and US can improve the efficacy of angiogenesis, even reverse the progress of cardiac dysfunction and pathological abnormalities, especially using the 26 cycle parameters. Under further study, this combined strategy might provide a novel approach for early intervention of DCM in diabetic patients.

Protective and Therapeutic Effects of Folic Acid on Cardiac Electrical and Structural Changes in a Rat Model of Diabetic-Cardiomyopathy

2021 ◽  
Vol 0 (0) ◽  
pp. 0-0
Author(s):  
Naness EL-Malkey ◽  
Mariam Michael ◽  
Maher Ibrahim ◽  
Rania Said Moawad ◽  
Maha Abdul Rahman ◽  
...  
Keyword(s):  
Folic Acid ◽  
Diabetic Cardiomyopathy ◽  
Rat Model ◽  
Structural Changes ◽  
Therapeutic Effects

scholarly journals Effects of Dipsacus asperoides Extract on Monosodium Iodoacetate–Induced Osteoarthritis in Rats Based on Gene Expression Profiling

2021 ◽  
Vol 12 ◽  
Author(s):  
Jin Mi Chun ◽  
A Yeong Lee ◽  
Jae Yong Nam ◽  
Kyung Seob Lim ◽  
Mu Seog Choe ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protective Effect ◽  
Gene Expression Profiling ◽  
Rat Model ◽  
Expression Profiling ◽  
Bone Fractures ◽  
Cartilage Tissue ◽  
Histopathological Analysis ◽  
Therapeutic Effects ◽  
Monosodium Iodoacetate

The root of Dipsacus asperoides C. Y. Cheng et T. M. Ai is traditionally used as an analgesic and anti-inflammatory agent to treat pain, rheumatoid arthritis, and bone fractures. However, neither its effects on osteoarthritis (OA) nor its effects on the arthritic cartilage tissue transcriptome have not been fully investigated. In this study, we used a rat model of monosodium iodoacetate- (MIA-) induced OA to investigate the therapeutic effects of a Dipsacus asperoides ethanolic extract (DAE, 200 mg/kg for 21 days). The study first assessed joint diameter, micro-CT scans, and histopathological analysis and then conducted gene expression profiling using RNA sequencing in articular cartilage tissue. We found that DAE treatment ameliorates OA disease phenotypes; it reduced the knee joint diameter and prevented changes in the structural and histological features of the joint, thereby showing that DAE has a protective effect against OA. Based on the results of gene expression profiling and subsequent pathway analysis, we found that several canonical pathways were linked to DAE treatment, including WNT/β-catenin signaling. Taken together, the present results suggest molecular mechanism, involving gene expression changes, by which DAE has a protective effect in a rat model of MIA-induced OA.

scholarly journals Cardioprotective effects of polydatin against myocardial injury in diabetic rats via inhibition of NADPH oxidase and NF-κB activities

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Ying-Ying Tan ◽  
Lei-Xin Chen ◽  
Ling Fang ◽  
Qi Zhang
Keyword(s):  
Nadph Oxidase ◽  
Diabetic Cardiomyopathy ◽  
High Glucose ◽  
Myocardial Injury ◽  
Diabetic Rats ◽  
Left Ventricular ◽  
Diabetic Patients ◽  
Therapeutic Effects ◽  
H9c2 Cells ◽  
Cardioprotective Effects

Abstract Background Diabetic cardiomyopathy is a main cause of the increased morbidity in diabetic patients, no effective treatment is available so far. Polydatin, a resveratrol glucoside isolated from the Polygonum cuspidatum, was found by our and others have antioxidant and cardioprotective activities. Therapeutic effects of polydatin on diabetic cardiomyopathy and the possible mechanisms remains unclear. This study aimed to investigate the cardioprotective effects and underlying mechanisms of polydatin on myocardial injury induced by hyperglycemia. Methods Diabetes in rats was made by high-fat diet combined with multiple low doses of streptozotocin, and then treated with polydatin (100 mg·kg-1·day-1, by gavage) for 8 weeks. Cardiac function was examined by echocardiography. Myocardial tissue and blood samples were collected for histology, protein and metabolic characteristics analysis. In cultured H9c2 cells with 30 mM of glucose, the direct effects of polydatin on myocyte injury were also observed. Results In diabetic rats, polydatin administration significantly improved myocardial dysfunction and attenuated histological abnormalities, as evidenced by elevating left ventricular shortening fraction and ejection fraction, as well as reducing cardiac hypertrophy and interstitial fibrosis. In cultured H9c2 cells, pretreatment of polydatin dose-dependently inhibited high glucose-induced cardiomyocyte injury. Further observation evidenced that polydatin suppressed the increase in the reactive oxygen species levels, NADPH oxidase activity and inflammatory cytokines production induced by hyperglycemia in vivo and in vitro. Polydatin also prevented the increase expression of NOX4, NOX2 and NF-κB in the high glucose -stimulated H9c2 cells and diabetic hearts. Conclusions Our results demonstrate that the cardioprotective effect of polydatin against hyperglycemia-induced myocardial injury is mediated by inhibition of NADPH oxidase and NF-κB activity. The findings may provide a novel understanding the mechanisms of the polydatin to be a potential treatment of diabetic cardiomyopathy.

Diallyl trisulfide and diallyl disulfide ameliorate cardiac dysfunction by suppressing apoptotic and enhancing survival pathways in experimental diabetic rats

2013 ◽  
Vol 114 (3) ◽  
pp. 402-410 ◽  
Author(s):  
Yao-Te Huang ◽  
Chun-Hsu Yao ◽  
Chia-Li Way ◽  
Kung-Wei Lee ◽  
Cheng-Yen Tsai ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Diabetic Cardiomyopathy ◽  
Biological Activities ◽  
Akt Signaling ◽  
Diabetic Rat ◽  
Diabetic Patients ◽  
Diallyl Disulfide ◽  
Therapeutic Effects ◽  
Diallyl Trisulfide ◽  
Akt Signaling Pathway

Cardiovascular disease is one of the major causes of mortality in diabetic patients. Mounting studies have shown that garlic exhibits, possibly through its antioxidant potential, diverse biological activities. In this study, we investigated the alleviating effects of garlic oil (GO) and its two major components, diallyl disulfide (DADS) and diallyl trisulfide (DATS), on diabetic cardiomyopathy in rats. Physiological cardiac parameters were obtained using echocardiography. Apoptotic cells were evaluated using TUNEL and DAPI staining. Protein expression levels were determined using Western blotting analysis. Our findings indicated that in diabetic rat hearts significantly decreased fractional shortening percentage, increased levels of nitrotyrosine, an elevated number of TUNEL-positive cells, enhanced levels of caspase 3 expression, and decreased PI3K-Akt signaling pathway activities were observed. Furthermore, all of these alterations were reversed following both GO and DATS (or DADS) administrations through increasing PI3K-Akt signaling pathway activities and inhibiting both the death receptor-dependent and the mitochondria-dependent apoptotic pathways. In conclusion, this study shows that DATS and DADS, with the efficacy order DATS > DADS, have the therapeutic potential for ameliorating diabetic cardiomyopathy. Furthermore, the therapeutic effects of GO on diabetic cardiomyopathy should be mainly from DATS and DADS.

Abstract 24: Hydrogen Sulfide Potentiates Bone Marrow-derived Angiogenic Progenitor Cell-mediated Ischemic Limb Angiogenesis in Diabetic Animals

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Zhongjian Cheng ◽  
Venkata NS Garikipati ◽  
Emily Nickoloff ◽  
Chunlin Wang ◽  
David Polhemus ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Bone Marrow ◽  
Hydrogen Sulfide ◽  
Critical Role ◽  
Tube Formation ◽  
Microvascular Endothelial Cell ◽  
Diabetic Patients ◽  
No Production ◽  
Therapeutic Effects ◽  
Microvascular Endothelial

Rationale: Critical hindlimb ischemia (CLI) represents an outcome of peripheral artery disease with a high incidence in diabetic patients. Recently, insufficient hydrogen sulfide (H 2 S) production has been implicated in cardiovascular disease. Objective: Explore the role of H 2 S in diabetes-induced bone marrow-derived angiogenic progenitor cells (BMAPC) dysfunction and its therapeutic effects on ischemic hindlimb injury of diabetes. Methods and Results: Diabetic BMAPCs from db/db mice showed decreased intracellular H 2 S production and blunted cystathionine γ-lyase (CSE) expression-an enzyme required for H 2 S generation. High glucose (HG) inhibited H 2 S production, migration and increased apoptosis of BMPAC that was rescued by H 2 S donor diallyl trisulfide (DATS) or overexpression of CSE. Administration DATS or local injection of diabetic BMAPCs overexpressing CSE significantly potentiated BMAPC-mediated blood flow recovery, capillary and arteriole formation, skeletal muscle architecture preservation, cell survival and decrease of perivascular infiltration of monocytes (CD68 + ) cells in ischemic skeletal muscle. Moreover, overexpression of CSE increased diabetic BMAPCs homing and engraftment in ischemic hindlimb. HG-impaired human cardiac microvascular endothelial cells (HCMVECs) tube formation and migration were rescued by DATS or overexpression of CSE. Mechanistically, HG increased threonine-495 phosphorylation of eNOS (eNOS-pT495) and inhibited nitric oxide (NO) production in HCMVECs which were rescued by DATS or overexpression of CSE. Silencing CSE by siRNA impaired tube formation and increased eNOS-pT495 expression in HCMVECs. Finally, HG-treated BMAPCs impaired mouse microvascular endothelial cell tube formation that was rescued by DATS. Conclusions: Our data suggests that CSE downregulation-induced H 2 S insufficient plays a critical role in diabetes-mediated BMAPC dysfunction. Administration of DATS or overexpression of CSE improves diabetic BMAPC-mediated angiogenesis/neovascularization via, at least partially, eNOS inactivation/NO reduction pathways. Our data indicate that H 2 S and overexpression of CSE in diabetic BMAPCs may open novel avenues for cell-based therapeutics of CLI in diabetic patients.

scholarly journals The protective effect of thalidomide on left ventricular function in a rat model of diabetic cardiomyopathy

2010 ◽  
Vol 12 (10) ◽  
pp. 1051-1060 ◽  
Author(s):  
Dae-Hee Kim ◽  
Yong-Jin Kim ◽  
Sung-A Chang ◽  
Hye-Won Lee ◽  
Ha-Na Kim ◽  
...  
Keyword(s):  
Left Ventricular Function ◽  
Protective Effect ◽  
Ventricular Function ◽  
Diabetic Cardiomyopathy ◽  
Rat Model ◽  
Left Ventricular

scholarly journals Bile Acids and Farnesoid X Receptor: Novel Target for the Treatment of Diabetic Cardiomyopathy

2019 ◽  
Vol 20 (10) ◽  
pp. 976-983 ◽  
Author(s):  
Chao Li ◽  
Yunlun Li ◽  
Zhibo Gai
Keyword(s):  
Oxidative Stress ◽  
Bile Acids ◽  
Diabetic Cardiomyopathy ◽  
Critical Role ◽  
Developed Countries ◽  
Farnesoid X Receptor ◽  
World Health ◽  
Common Disease ◽  
Diabetic Patients ◽  
Regulatory Effect

Diabetes mellitus (DM) has become an increasingly common disease with high disability and mortality rates. Diabetes complications are the main cause of diabetes death and about 50% of diabetic patients died from heart disease in developed countries reported by World Health Organization. Diabetic cardiomyopathy (DCM) has been considered as a high incidence and serious complication of DM and plays a key role in the incidence and development of diabetes related heart failure. Metabolism dysregulation is regarded as an important and earlier factor occurred in the pathogenesis of DCM. Insulin resistance, oxidative stress, inflammation and mitochondrial dysfunction also contribute to the development of DCM. Farnesoid X Receptor (FXR) is a member of nuclear receptor superfamily, and plays a critical role in regulating lipid and glucose metabolism, oxidative stress and inflammation. FXR is activated by primary bile acids (BAs) such as chenodeoxycholic acid, cholic acid and synthetic agonists such as obeticholic acid. BAs are the main active ingredients of many natural products and traditional medicines, especially bile or gallstones in animals, such as calculus bovis. Due to the regulatory effect of FXR on glucose and lipid metabolism, oxidative stress and inflammation, the treatment of BAs and FXR agonists for metabolic syndrome and DCM have gained more attention. This review will focus on the pathogenesis of diabetic cardiomyopathy and the regulatory effect of BAs and FXR on DCM.

scholarly journals Protective effect of resveratrol on estrogen deficiency-induced osteoporosis though attenuating NADPH oxidase 4/nuclear factor kappa B pathway by increasing miR-92b-3p expression

2020 ◽  
Vol 34 ◽  
pp. 205873842094176
Author(s):  
Ye Zhang ◽  
Ming-wei Liu ◽  
Yun He ◽  
Ning Deng ◽  
Yan Chen ◽  
...  
Keyword(s):  
Protein Expression ◽  
Protective Effect ◽  
Rat Model ◽  
Cathepsin K ◽  
Estrogen Deficiency ◽  
Pathological Examination ◽  
Enzyme Linked Immunosorbent Assay ◽  
Therapeutic Effects ◽  
Trabecular Thickness ◽  
Gene And Protein Expression

Introduction: Resveratrol (RES) exhibits estrogen-like effects and has potential applications to treatment of osteoporosis caused by estrogen deficiency; however, the specific mechanism of action of RES remains unclear. Here, we examined the therapeutic effects of RES on ovariectomized (OVX) rats with osteoporosis and determined the underlying mechanism. Methods: We established an OVX rat model to study osteoporosis caused by estrogen deficiency. The treatment groups were given orally with RES (50, 100, and 200 mg/day), the estrogen group received 0.8 mg/kg E2 daily via oral route, and the sham-operated and control groups received an equivalent dose of sodium carboxymethylcellulose orally. After 12 weeks of treatment, we used real-time quantitative polymerase chain reaction (PCR) and Western blot analysis to measure the gene and protein expression of miR-92b-3p, Nox4, NF-κBp65, IκB, BMP2, Smad7, and RUNX-2 in bone tissues. Right femur structural parameters were evaluated by micro-CT. Dual-energy X-ray 4500 W was used to determine systemic bone mineral density (BMD). Enzyme-linked immunosorbent assay (ELISA) kits were used to determine the serum levels of bone alkaline phosphatase (BALP), osteoprotegerin (OPG), anti-tartrate acid phosphatase-5b (PTRA5b), and carboxylated terminal peptide (CTX-I). The rat femoral bone specimens were stained using hematoxylin and eosin for pathological examination Results: We observed increased levels of serum estrogen in both ovaries, elevated miR-92b-3p levels in bone tissues, reduced levels of Nox4, NF-κBp65, p-IκB-a, and cathepsin K, and elevated gene and protein expression of BMP2, Smad7, and RUNX-2 in the OVX rat model of osteoporosis after treatment with RES. Elevated levels of BALP, OPG, ALP, and BMD along with reduced levels of TRAP-5b and CTX-I were also observed. The structural model index (SMI) and the trabecular space (Tb. Sp) decreased, while the trabecular thickness (Tb. Th), bone volume fraction (BV/TV), trabecular number (Tb.N), and tissue bone density (Conn.D) increased, thereby improving osteoporosis induced by estrogen deficiency in both ovaries. Conclusion: Cathepsin K expression and Nox4/NF-κB signaling pathway were suppressed by the elevated expression of miR-92b-3p. This inhibition was pivotal in the protective effect of RES against osteoporosis induced by estrogen deficiency in both ovaries. Thus, RES efficiently alleviated osteoporosis induced by estrogen deficiency in rats.

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