Diabetic Cardiovascular Complications Research Articles

Central role of cardiac fibroblasts in myocardial fibrosis of diabetic cardiomyopathy.

Diabetic cardiomyopathy (DCM), a main cardiovascular complication of diabetes, can eventually develop into heart failure and affect the prognosis of patients. Myocardial fibrosis is the main factor causing ventricular wall stiffness and heart failure in DCM. Early control of myocardial fibrosis in DCM is of great significance to prevent or postpone the progression of DCM to heart failure. A growing body of evidence suggests that cardiomyocytes, immunocytes, and endothelial cells involve fibrogenic actions, however, cardiac fibroblasts, the main participants in collagen production, are situated in the most central position in cardiac fibrosis. In this review, we systematically elaborate the source and physiological role of myocardial fibroblasts in the context of DCM, and we also discuss the potential action and mechanism of cardiac fibroblasts in promoting fibrosis, so as to provide guidance for formulating strategies for prevention and treatment of cardiac fibrosis in DCM.

Circadian rhythm of plasminogen activator inhibitor-1 and cardiovascular complications in type 2 diabetes.

Cardiovascular complications are a common death cause in type 2 diabetes patients, as they are often combined. Plasminogen-activator Inhibitor 1 (PAI-1) participates in the development and progression of cardiovascular complications in diabetes. Insulin resistance increases PAI-1 production, and high PAI-1 levels lead to an environment conducive to thrombosis and earlier and more severe vascular disease. Current evidence also suggests that PAI-1 has a rhythmic profile of circadian fluctuations and acrophase in the morning within a single day, which might explain the high morning incidence of cardiovascular events. Thus, PAI-1 is a possible drug target. Although several PAI-1 inhibitors have been developed, none have yet been allowed for clinical use. Research on rhythm has also led to the concept of "chronotherapy", a rhythm-based drug regimen expected to improve the treatment of cardiovascular complications in diabetic patients. Herein, we searched several databases and reviewed relevant articles to describe the circadian rhythm characteristics and endogenous molecular mechanisms of PAI-1, its relationship with insulin resistance, the causes of cardiovascular complications caused by PAI-1, and the current development of PAI-1 inhibitors. We also summarized the possibility of using the circadian rhythm of PAI-1 to treat cardiovascular complications in diabetic patients.

Hyperglycemia-Suppressed SMARCA5 Disrupts Transcriptional Homeostasis to Facilitate Endothelial Dysfunction in Diabetes.

Dysfunction of vascular endothelial cells (ECs) plays a central role in the pathogenesis of cardiovascular complications in diabetes. SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 5 (SMARCA5) is a key regulator of chromatin structure and DNA repair, but its role in ECs remains surprisingly unexplored. The current study was designed to elucidate the regulated expression and function of SMARCA5 in diabetic ECs. SMARCA5 expression was evaluated in ECs from diabetic mouse and human circulating CD34+ cells using quantitative reverse transcription polymerase chain reaction and Western blot. Effects of SMARCA5 manipulation on ECs function were evaluated using cell migration, in vitro tube formation and in vivo wound healing assays. Interaction among oxidative stress, SMARCA5 and transcriptional reprogramming was elucidated using luciferase reporter assay, electrophoretic mobility shift assay and chromatin immunoprecipitation. Endothelial SMARCA5 expression was significantly decreased in diabetic rodents and humans. Hyperglycemia-suppressed SMARCA5 impaired EC migration and tube formation in vitro, and blunted vasculogenesis in vivo. Contrarily, overexpression of SMARCA5 in situ by a SMARCA5 adenovirus-incorporated hydrogel effectively promoted the rate of wound healing in a dorsal skin punch injury model of diabetic mice. Mechanistically, hyperglycemia-elicited oxidative stress suppressed SMARCA5 transactivation in a signal transducer and activator of transcription 3 (STAT3)-dependent manner. Moreover, SMARCA5 maintained transcriptional homeostasis of several pro-angiogenic factors through both direct and indirect chromatin-remodeling mechanisms. In contrast, depletion of SMARCA5 disrupted transcriptional homeostasis to render ECs unresponsive to established angiogenic factors, which ultimately resulted in endothelial dysfunction in diabetes. Suppression of endothelial SMARCA5 contributes to, at least in part, multiple aspects of endothelial dysfunction, which may thereby exacerbate cardiovascular complications in diabetes.

Hypomagnesemia as a Risk Factor and Accelerator for Vascular Aging in Diabetes Mellitus and Chronic Kidney Disease.

The age-old axiom that one is as old as his or her vessels are, calls for ongoing critical re-examination of modifiable risk factors of accelerated vascular ageing in chronic kidney diseases. Attempts to modulate vascular risk with cholesterol-lowering agents have largely failed in advanced chronic kidney disease (CKD). In addition to nitrogen waste products, many pathological biochemical processes also play a role in vascular calcification in chronic kidney damage. Magnesium, a cation vital for the body, may substantially reduce cardiovascular diseases' risk and progression. This narrative review aimed to address the relationship between hypomagnesemia and vascular calcification, which promotes further cardiovascular complications in diabetes, aging, and CKD. Articles with predefined keywords were searched for in the PubMed and Google Scholar databases with specific inclusion and exclusion criteria. We hypothesized that a decrease in serum magnesium levels contributes to increased vascular calcification and thereby increases cardiovascular mortality. In summary, based on existing evidence in the literature, it appears that simple and inexpensive oral magnesium supplementation may reduce the cardiovascular mortality of patients who are already severely affected by such diseases; in this context, the concept of 'normal' vs. 'ideal' serum magnesium levels should be carefully re-examined.

MicroRNA-494 regulates high glucose-induced cardiomyocyte apoptosis and autophagy by PI3K/AKT/mTOR signalling pathway.

Diabetic cardiomyopathy (DCM) is one of the major cardiovascular complications of diabetes. However, the mechanism of DCM is not fully understood. Studies have confirmed that certain microRNAs (miRNAs/miRs) are key regulators of DCM. The aim of this study was to investigate the role and mechanism of microRNA (miR)-494 in cardiomyocyte apoptosis and autophagy induced by high glucose (HG). By establishing a rat DCM model and an HG-treated H9c2 cells injury model, cardiac function was detected by echocardiography, myocardial tissue was stained by immunohistochemistry, and Cell Counting Kit-8 assay and lactate dehydrogenase assay were used to detect the cardiomyocyte injury. Cell apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labelling staining, and western blotting was used to detect death and autophagy. The results showed that the expression level of miR-494 was higher in the myocardial tissue of DCM rats and the myocardial cells of H9c2 treated with HG. Compared with the corresponding negative control groups, miR-494 mimics enhanced HG-induced apoptosis and autophagy, whereas miR-494 inhibitors showed the opposite effect, corresponding PI3K, AKT, and mTOR phosphorylation level has changed. These findings identify that miR-494 could regulate cell apoptosis and autophagy through PI3K/AKT/mTOR signalling pathway, participating in the regulation of cardiomyocyte cell damage after HG. These findings provide new insights for the further study of the molecular mechanism and treatment of DCM.

Role of mitochondrial metabolic disorder and immune infiltration in diabetic cardiomyopathy: new insights from bioinformatics analysis

BackgroundDiabetic cardiomyopathy (DCM) is one of the common cardiovascular complications of diabetes and a leading cause of death in diabetic patients. Mitochondrial metabolism and immune-inflammation are key for DCM pathogenesis, but their crosstalk in DCM remains an open issue. This study explored the separate roles of mitochondrial metabolism and immune microenvironment and their crosstalk in DCM with bioinformatics.MethodsDCM chip data (GSE4745, GSE5606, and GSE6880) were obtained from NCBI GEO, while mitochondrial gene data were downloaded from MitoCarta3.0 database. Differentially expressed genes (DEGs) were screened by GEO2R and processed for GSEA, GO and KEGG pathway analyses. Mitochondria-related DEGs (MitoDEGs) were obtained. A PPI network was constructed, and the hub MitoDEGs closely linked to DCM or heart failure were identified with CytoHubba, MCODE and CTD scores. Transcription factors and target miRNAs of the hub MitoDEGs were predicted with Cytoscape and miRWalk database, respectively, and a regulatory network was established. The immune infiltration pattern in DCM was analyzed with ImmuCellAI, while the relationship between MitoDEGs and immune infiltration abundance was investigated using Spearman method. A rat model of DCM was established to validate the expression of hub MitoDEGs and their relationship with cardiac function.ResultsMitoDEGs in DCM were significantly enriched in pathways involved in mitochondrial metabolism, immunoregulation, and collagen synthesis. Nine hub MitoDEGs closely linked to DCM or heart failure were obtained. Immune analysis revealed significantly increased infiltration of B cells while decreased infiltration of DCs in immune microenvironment of DCM. Spearman analysis demonstrated that the hub MitoDEGs were positively associated with the infiltration of pro-inflammatory immune cells, but negatively associated with the infiltration of anti-inflammatory or regulatory immune cells. In the animal experiment, 4 hub MitoDEGs (Pdk4, Hmgcs2, Decr1, and Ivd) showed an expression trend consistent with bioinformatics analysis result. Additionally, the up-regulation of Pdk4, Hmgcs2, Decr1 and the down-regulation of Ivd were distinctly linked to reduced cardiac function.ConclusionsThis study unraveled the interaction between mitochondrial metabolism and immune microenvironment in DCM, providing new insights into the research on potential pathogenesis of DCM and the exploration of novel targets for medical interventions.

Cholesterol Redistribution in Pancreatic β-Cells: A Flexible Path to Regulate Insulin Secretion.

Pancreatic β-cells, by secreting insulin, play a key role in the control of glucose homeostasis, and their dysfunction is the basis of diabetes development. The metabolic milieu created by high blood glucose and lipids is known to play a role in this process. In the last decades, cholesterol has attracted significant attention, not only because it critically controls β-cell function but also because it is the target of lipid-lowering therapies proposed for preventing the cardiovascular complications in diabetes. Despite the remarkable progress, understanding the molecular mechanisms responsible for cholesterol-mediated β-cell function remains an open and attractive area of investigation. Studies indicate that β-cells not only regulate the total cholesterol level but also its redistribution within organelles, a process mediated by vesicular and non-vesicular transport. The aim of this review is to summarize the most current view of how cholesterol homeostasis is maintained in pancreatic β-cells and to provide new insights on the mechanisms by which cholesterol is dynamically distributed among organelles to preserve their functionality. While cholesterol may affect virtually any activity of the β-cell, the intent of this review is to focus on early steps of insulin synthesis and secretion, an area still largely unexplored.

MOTS-c repairs myocardial damage by inhibiting the CCN1/ERK1/2/EGR1 pathway in diabetic rats.

Cardiac structure remodeling and dysfunction are common complications of diabetes, often leading to serious cardiovascular events. MOTS-c, a mitochondria-derived peptide, regulates metabolic homeostasis by accelerating glucose uptake and improving insulin sensitivity. Plasma levels of MOTS-c are decreased in patients with diabetes. MOTS-c can improve vascular endothelial function, making it a novel therapeutic target for the cardiovascular complications of diabetes. We investigated the effects of MOTS-c on cardiac structure and function and analyzed transcriptomic characteristics in diabetic rats. Our results indicate that treatment with MOTS-c for 8-week repaired myocardial mitochondrial damage and preserved cardiac systolic and diastolic function. Transcriptomic analysis revealed that MOTS-c altered 47 disease causing genes. Functional enrichment analysis indicated MOTS-c attenuated diabetic heart disease involved apoptosis, immunoregulation, angiogenesis and fatty acid metabolism. Moreover, MOTS-c reduced myocardial apoptosis by downregulating CCN1 genes and thereby inhibiting the activation of ERK1/2 and the expression of its downstream EGR1 gene. Our findings identify potential therapeutic targets for the treatment of T2D and diabetic cardiomyopathy.

Epicardial Adipose Tissue and Diabetic Cardiomyopathy.

Diabetes is a long-term chronic disease, and cardiovascular disease is the leading cause of death. Diabetic cardiomyopathy (DCM), one of the cardiovascular complications of diabetes, has many uncertain factors. Epicardial fat, as the heart fat bank, functions as fatty tissue and is the heart's endocrine organ. The existence of diabetes affects the distribution of heart fat and promotes the secretion of adipokine. In different pathological conditions, it can promote the secretion of pro-inflammatory adipokine, reactive oxygen species, oxidative stress, and even autophagy, thus affecting cardiac function. In this paper, we will elaborate on the mechanism of epicardial fat in the pathogenesis of diabetic cardiomyopathy.

Serum Pentosidine is Associated with Cardiac Dysfunction and Atherosclerosis in T2DM.

The purpose of this paper is to investigate the relationship between serum pentosidine levels and cardiac function and vascular disease in diabetic patients, and to provide a new reference indicator for the early detection of diabetic cardiovascular complications. This was a cross-sectional study. One hundred and twenty-two patients with type 2 diabetes were grouped by LVEF quartiles to compare the differences between their clinical data and serum pentosidine levels. Also, the correlation between serum pentosidine and clinical indicators was assessed. The effect of serum pentosidine on cardiac function and vascular stiffness was analyzed by multiple stepwise regression. Serum pentosidine levels were higher in patients with LVEF ≤57%. Serum pentosidine levels were positively correlated with waist-to-hip ratio, hemoglobin, AIP, baPWV, LVESD, and ARD, and negatively correlated with LVEF. Low serum pentosidine was associated with increased LVESD; high pentosidine was significantly associated with increased ARD, high AIP and high baPWV. The results suggest that serum pentosidine, a member of AGEs, may reflect cardiac remodeling and dysfunction as well as atherosclerosis.

Ambulatory Blood Pressure Monitoring as Predictor of Diabetic Cardiovascular Complications

Ambulatory Blood Pressure Monitoring as Predictor of Diabetic Cardiovascular Complications

Real role of growth factor receptor-binding protein 10: Linking lipid metabolism to diabetes cardiovascular complications.

Cardiovascular complications of patients with type 2 diabetes mellitus (T2DM) threaten the health and life of numerous individuals. Recently, growth factor receptor-binding protein 10 (GRB10) was found to play a pivotal role in vascular complications of T2DM, which participates in the regulation of lipid metabolism of T2DM patients. The genetic variation of GRB10 rs1800504 is closely related to the risk of coronary heart disease in patients with T2DM. The development of GRB10 as a key mediator in the association of lipid metabolism with cardiovascular complications in T2DM is detailed in and may provide new potential concerns for the study of cardiovascular complications in T2DM patients.

Salvianolic acid A regulates pyroptosis of endothelial cells via directly targeting PKM2 and ameliorates diabetic atherosclerosis.

Rescuing endothelial cells from pyroptotic cell death emerges as a potential therapeutic strategy to combat diabetic atherosclerosis. Salvianolic acid A (SAA) is a major water-soluble phenolic acid in the Salvia miltiorrhiza Bunge, which has been used in traditional Chinese medicine (TCM) and health food products for a long time. This study investigated whether SAA-regulated pyruvate kinase M2 (PKM2) functions to protect endothelial cells. In streptozotocin (STZ)-induced diabetic ApoE-/- mice subjected to a Western diet, SAA attenuated atherosclerotic plaque formation and inhibited pathological changes in the aorta. In addition, SAA significantly prevented NLRP3 inflammasome activation and pyroptosis of endothelial cells in the diabetic atherosclerotic aortic sinus or those exposed to high glucose. Mechanistically, PKM2 was verified to be the main target of SAA. We further revealed that SAA directly interacts with PKM2 at its activator pocket, inhibits phosphorylation of Y105, and hinders the nuclear translocation of PKM2. Also, SAA consistently decreased high glucose-induced overproduction of lactate and partially lactate-dependent phosphorylation of PKR (a regulator of the NLRP3 inflammasome). Further assay on Phenylalanine (PKM2 activity inhibitor) proved that SAA exhibits the function in high glucose-induced pyroptosis of endothelial cells dependently on PKM2 regulation. Furthermore, an assay on c16 (inhibitor of PKR activity) with co-phenylalanine demonstrated that the regulation of the phosphorylated PKR partially drives PKM2-dependent SAA modulation of cell pyroptosis. Therefore, this article reports on the novel function of SAA in the pyroptosis of endothelial cells and diabetic atherosclerosis, which provides important insights into immunometabolism reprogramming that is important for diabetic cardiovascular disease complications therapy.

Mutual Regulation between Redox and Hypoxia-Inducible Factors in Cardiovascular and Renal Complications of Diabetes.

Oxidative stress and hypoxia-inducible factors (HIFs) have been implicated in the pathogenesis of diabetic cardiovascular and renal diseases. Reactive oxygen species (ROS) mediate physiological and pathophysiological processes, being involved in the modulation of cell signaling, differentiation, and survival, but also in cyto- and genotoxic damage. As master regulators of glycolytic metabolism and oxygen homeostasis, HIFs have been largely studied for their role in cell survival in hypoxic conditions. However, in addition to hypoxia, other stimuli can regulate HIFs stability and transcriptional activity, even in normoxic conditions. Among these, a regulatory role of ROS and their byproducts on HIFs, particularly the HIF-1α isoform, has received growing attention in recent years. On the other hand, HIF-1α and HIF-2α exert mutually antagonistic effects on oxidative damage. In diabetes, redox-mediated HIF-1α deregulation contributes to the onset and progression of cardiovascular and renal complications, and recent findings suggest that deranged HIF signaling induced by hyperglycemia and other cellular stressors associated with metabolic disorders may cause mitochondrial dysfunction, oxidative stress, and inflammation. Understanding the mechanisms of mutual regulation between HIFs and redox factors and the specific contribution of the two main isoforms of HIF-α is fundamental to identify new therapeutic targets for vascular complications of diabetes.

Associations of Obesity Indices with Bone Mineral Densities and Risk of Osteoporosis Stratified Across Diabetic Vascular Disease in T2DM Patients.

To evaluate associations of obesity indices with bone mineral densities (BMD) and risk of osteoporosis in T2DM patients totally and stratified across presence of any diabetic cardiovascular complications. Cross-sectional analyses of baseline information on a cohort of 250 T2DM patients were conducted in Xiamen, China. Obesity indices included body weight, height, body mass index (BMI), waist and waist hip ratio (WHR). BMD was measured using dual-energy X-ray absorptiometry at three different sites, and osteoporosis was defined based on the minimum T-scores of BMD. Presence of any diabetic vascular complications was confirmed by checking their medical records histories. Among the 250 T2DM patients, 50 (20.0%) were defined as osteoporosis. Multivariable linear regression and multivariable logistic regression analyses showed that igher obesity indices, including body weight, BMI and waist, but neither body height nor waist hip ratio, were positively associated with the minimum T-scores of BMD and had significantly decreased risk of osteoporosis. Stratified analyses across presence of any of diabetic vascular complications showed similar results for those with any of diabetic vascular complications, while no significant association between obesity indices and minimum T-scores of BMD was found for those without. Postmenopausal women (vs men) and ever drinking were significantly associated with increased risk of osteoporosis, and the adjusted odds ratios (95% CIs) were 5.165 (1.762-15.138, p = 0.003) and 3.789 (1.087-13.214, p = 0.037), respectively. None of metabolic profiles, including systolic and diastolic blood pressure, triglyceride, total cholesterol, high-density lipoprotein cholesterol, HbA1c and blood uric acid, was significantly associated with either minimum T-scores of BMD or risk of osteoporosis. Associations of obesity indices with either BMD or risk of osteoporosis in T2DM patients varied by presence of any diabetic vascular complication and should be not interpreted as causal without considering the often-unmeasured effect modification by health status.

Resveratrol improves diabetic cardiomyopathy by preventing asymmetric dimethylarginine-caused peroxisome proliferator-activated receptor-γ coactivator-1α acetylation

ObjectivesCardiac protection of resveratrol is related to the improvement of mitochondrial function through sirtuin1 (SIRT1) activation and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) deacetylation. Asymmetric dimethylarginine (ADMA) as an endogenous inhibitor of nitric oxide synthases is associated with diabetic cardiovascular complications and has a cross-talk with lysine acetylation. This study was to determine whether resveratrol reverses ADMA's pathogenic role in diabetic cardiomyopathy and elucidate the underlying mechanisms in type 2 diabetic (T2DM) rats and cardiomyocytes. MethodsT2DM Rats were induced by high-fat diet plus small-dose streptozotocin injection (35 mg/kg). Resveratrol was given by gavage (50 mg/kg/d) to some rats for 16w. Cardiac function was measured by echocardiography, and PGC-1α acetylation was detected by immunoprecipitation. Mitochondrial DNA and ATP contents were analyzed to evaluate mitochondrial biogenesis and function. ResultsEndogenous ADMA accumulation and its signal disorders were associated with cardiac and mitochondrial dysfunctions in accompany with increased PGC-1α acetylation and decreased PGC-1α expression in the myocardium of T2DM rats compared with control rats. Resveratrol treatment attenuated ADMA accumulation, cardiac and mitochondrial dysfunctions in parallel with reversing altered PGC-1α expression and acetylation in the myocardium of T2DM rats. Exogenous ADMA not only reproduced mitochondrial dysfunction and cardiac hypertrophy but also reduced PGC-1α expression and enhanced PGC-1α acetylation in accompany of down-regulating SIRT1 and up-regulating acetyltransferase expression, all of which could be prevented by resveratrol pretreatment in cardiomyocytes. ConclusionsThese results indicate that ADMA promotes PGC-1α acetylation as a potential therapeutic target for resveratrol of management diabetic cardiomyopathy in T2DM rats.

Exosomes from human umbilical cord mesenchymal stem cells protect aortas in Db/db mice characterized by combination of metabolomics and proteomics

Diabetic cardiovascular complication is a common systemic disease with high morbidity and mortality worldwide. We hypothesise that exosomes derived from human umbilical cord mesenchymal stem cells (hUCMSCs-exos) can rescue these disorders and alleviate vascular remodeling in diabetes. Morphological, non-targeted metabolomics and 4D label-free proteomics techniques were used to analyze the aortas of db/m mice as normal control group (NCA), saline treated db/db mice (DMA), and hUCMSCs-exos treated db/db mice (DMTA), and to clarify the molecular mechanism of the protection of hUCMSCs-exos in vascular remodeling from a new point of view. The results showed that 74 metabolites were changed significantly in diabetic aortas, of which 15 were almost restored by hUCMSCs-exos. In proteomics, 30 potential targets such as Stromal cell-derived factor 2-like protein 1, Leukemia inhibitory factor receptor, Peroxisomal membrane protein and E3 ubiquitin-protein ligase MYCBP2 were detected. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway-based analysis showed that Central carbon metabolism in cancer and Galactose metabolism pathway were up-regulated to near normal by hUCMSCs-exos in metabolomics, with janus associated kinase-signal transducer and activator of transcription (JAK-STAT) pathway displayed in proteomics. According to bioinformatics and integrated analysis, these targeted molecules of hUCMSCs-exos to attenuate the vascular remodeling were mainly associated with regulation of energy metabolism, oxidative stress, inflammation, and cellular communications. This study provided a reference for the therapy of diabetes-induced cardiovascular complications.

Integrating pharmacological evaluation and computational identification for deciphering the action mechanism of Yunpi-Huoxue-Sanjie formula alleviates diabetic cardiomyopathy.

Background: Yunpi-Huoxue-Sanjie (YP-SJ) formula is a Chinese herbal formula with unique advantages for the treatment of diabetic cardiovascular complications, such as Diabetic cardiomyopathy (DCM). However, potential targets and molecular mechanisms remain unclear. Therefore, our research was designed to evaluate rat myocardial morphology, fat metabolism and oxidative stress to verify myocardial protective effect of YP-SJ formula in vivo. And then to explore and validate its probable mechanism through network pharmacology and experiments in vitro and in vivo. Methods: In this study, DCM rats were randomly divided into five groups: control group, model group, and three YP-SJ formula groups (low-dose, middle-dose, and high-dose groups). Experimental rats were treated with 6 g/kg/d, 12 g/kg/d and 24 g/kg/d YP-SJ formula by gavage for 10 weeks, respectively. Cardiac function of rats was measured by high-resolution small-animal imaging system. The cells were divided into control group, high glucose group, high glucose + control serum group, high glucose + dosed serum group, high glucose + NC-siRNA group, high glucose + siRNA-FoxO1 group. The extent of autophagy was measured by flow cytometry, immunofluorescence, and western blotting. Results: It was found that YP-SJ formula could effectively improve cardiac systolic function in DCM rats. We identified 46 major candidate YP-SJ formula targets that are closely related to the progression of DCM. Enrichment analysis revealed key targets of YP-SJ formula related to environmental information processing, organic systems, and the metabolic occurrence of reactive oxygen species. Meanwhile, we verified that YP-SJ formula can increase the expression of forkhead box protein O1 (FoxO1), autophagy-related protein 7 (Atg7), Beclin 1, and light chain 3 (LC3), and decrease the expression of phosphorylated FoxO1 in vitro and in vivo. The results showed that YP-SJ formula could activate the FoxO1 signaling pathway associated with DCM rats. Further experiments showed that YP-SJ formula could improve cardiac function by regulating autophagy. Conclusion: YP-SJ formula treats DCM by modulating targets that play a key role in autophagy, improving myocardial function through a multi-component, multi-level, multi-target, multi-pathway, and multi-mechanism approach.

Macrophage Glucose Metabolism Reprogramming and Cardiovascular Complications of Diabetes

Macrophages are the main participants in the pathogenesis of many chronic inflammatory and autoimmune diseases, including diabetes, and cardiovascular complications mediated by abnormal activation of macrophages caused by various reasons are the main causes of morbidity and death in patients with diabetes. Different environmental stimuli can easily lead to glucose metabolism reprogramming in macrophages, resulting in a series of changes in metabolization-related enzymes, metabolites and metabolic pathways. Glucose metabolism reprogramming is closely related to M1 polarization and M2 polarization of macrophages, for example, M1 macrophages tend to anaerobic glycolysis while M2 macrophages tend to aerobic metabolism, and different polarization of macrophages is closely related to various diseases. Therefore, this paper reviews the mechanism and inducing factors of reprogramming of glucose metabolic pathways, as well as the effect of these pathways on macrophage polarization, so as to provide services for clinical research and treatment of the occurrence and development of cardiovascular complications in the context of chronic inflammation of diabetes.

Ameliorative potentials of the ethanolic extract from Lycium chinense leaf extract against diabetic cardiomyopathy. Insight into oxido-inflammatory and apoptosis modulation

The prevalence of cardiovascular complications in diabetes has become one of the major cause of diabetes related morbidity/mortality. The onset and progression of diabetic cardiomyopathy (DCM) has been majorly linked to lipid alterations, oxidative stress, inflammation and apoptosis. This present study investigated the cardioprotective role of Lycium chinense leaf extract (LCME) in fructose/streptozotocin induced diabetic rats. Diabetic animals were orally gavaged with LCME (100 and 400 mg/kg) for five weeks. The results indicated that diabetic rats showed increased blood glucose concentration, serum cardiac function markers (troponin T, creatine kinase-MB, aspartate aminotransferase and lactate dehydrogenase) and lipid profile (triglycerides and cholesterol). In addition, the cardiac tissues of diabetic rats showed increased levels of nuclear factor-κB (NF-κB), tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL 1β), interleukin 6 (IL-6), caspase-3 and malondialdehyde as well as significantly reduced activities of catalase, superoxide dismutase, reduced glutathione and glutathione peroxidase. LCME significantly ameliorated hyperglycemia and markedly decreased serum concentrations of troponin T, creatine kinase-MB, aspartate aminotransferase and lactate dehydrogenase, triglycerides and cholesterol. Furthermore, LCME notably suppressed cardiac oxido-inflammatory mediators and boosted cardiac antioxidant defense. Histopathologically, LCME restored cardiac structural alterations and also suppressed the immunohistochemical expression of collagen IV, smooth muscle alpha-actin (α-SMA) and p53, while Bcl2 expression was significantly increased. In conclusion, our result indicated that LCME protected against diabetic cardiomyopathy suppressing oxidative stress, inflammation, apoptosis and fibrosis.