• 3-SRA-2023-1417-S-B Breakthrough-T1D
• RFA-DK-23-021 Special Diabetes Program for Type 1 Diabetes
• The Leona M. & Harry B. Helmsley Charitable Trust
• U24 DK133700 NIDDK NIH HHS
• U24 DK133700 National Institutes of Diabetes and Digestive and Kidney Diseases
• U24 DK133700 National Institutes of Diabetes and Digestive and Kidney Diseases

• Angiogenesis
• Diabetes mellitus
• Diabetic foot ulcers
• Diabetic wound
• Timing of treatment

• AGEs
• AOPP
• Chaostheory
• albuminuria
• glycoxidation
• microvascular complications
• type 2 diabetes

• Diabetic cardiomyopathy
• Inflammatory
• Pyroptosis
• Therapeutic strategy

• Pyroptosis/drug effects
• Pyroptosis/physiology
• Diabetic Cardiomyopathies/therapy
• Diabetic Cardiomyopathies/prevention & control
• Humans
• Animals
• Signal Transduction/drug effects
• Myocardium/pathology
• Myocardium/metabolism

• HFpEF
• HFrEF
• SGLT2-i
• continuous monitoring of ketone levels
• diabetic cardiomyopathy
• diabetic ketoacidosis
• epidemiologic studies
• heart failure
• hospitalization
• ketonemia
• patient education
• sodium–glucose cotransporter-2 inhibitors
• type 1 diabetes

• King Saud University

• Diabetic kidney disease
• Gut microbiota
• Metabolites
• Pathway
• Therapeutics

• Humans
• Diabetic Nephropathies/metabolism
• Biomarkers/metabolism
• Gastrointestinal Microbiome
• Metabolomics/methods

• AGE
• AGER
• PET
• RAGE
• SPECT
• fluorescence
• molecular imaging

• Humans
• Glycation End Products, Advanced/metabolism
• Receptor for Advanced Glycation End Products/metabolism
• Maillard Reaction
• Diabetes Mellitus/metabolism
• Inflammation

• Cancer Center at Illinois
• DIR/WK/2017/01 Polish Ministry of Education and Science
• 10/E-389/SPUB/SP/2020 Polish Ministry of Education and Science

• diabetes
• human bone mesenchymal stem cell-derived extracellular vesicles
• human coronary artery endothelial cells
• metabolic syndrome

• Animals
• Humans
• Coronary Vessels/metabolism
• Endothelial Cells/metabolism
• Cells, Cultured
• Extracellular Vesicles/metabolism
• Mesenchymal Stem Cells/metabolism
• Diabetes Mellitus/metabolism

• R01 HL046716 NHLBI NIH HHS
• T32 HL160517 NHLBI NIH HHS
• R56 HL133624 NHLBI NIH HHS
• T32 GM065085 NIGMS NIH HHS
• R01 HL128831 NHLBI NIH HHS
• R24 GM137786 NIGMS NIH HHS
• HHS | National Institutes of Health (NIH)
• Rhode Island Foundation

• Obstructive coronary artery disease
• pericoronary adipose tissue
• plain computed tomography
• preliminary screening
• radiomics
• type 2 diabetes

• Advanced glycation end products
• Anti-advanced glycation end products strategies
• Cardiovascular complications
• Endothelial cells
• Hyperglycemia
• Oxidative stress
• Reactive oxygen species
• Receptor of advanced glycation end products
• Type 2 diabetes mellitus

• autophagy
• diabetes
• endothelial cells
• pathological characteristics
• vascular endothelial injury

• Humans
• Quality of Life
• Diabetes Mellitus
• Insulin Resistance
• Oxidative Stress
• Vascular System Injuries
• Autophagy

Background: Diabetes mellitus leads to endothelial dysfunction and accumulation of oxygen radicals. Sulfasalazine-induced Nrf2 activation reduces oxidative stress in vessels. Thus, in the present study, we investigated the effects of sulfasalazine on endothelial dysfunction induced by high glucose. We also ascribed the underlying mechanism involved in glucose-induced endothelial dysfunction.

Methods: For this experiment we used 80 Wistar Albino rats thoracic aorta to calculate the dose response curve of noradrenaline and acetylcholine. Vessels were incubated in normal and high glucose for 2 h. To investigate glucose and sulfasalazine effects the vessels of the high glucose group were pre-treated with sulfasalazine (300 mM), JNK inhibitor (SP600125), and ERK inhibitor (U0126) for 30 min. The dose response curve was calculated through organ bath. The eNOS, TAS, TOS, and HO-1 levels were estimated by commercially available ELISA kits.

Results: In the high glucose group, the E_max for contraction was significantly higher (p < 0.001), and E_max for relaxation was lower than that of control. These functional changes were parallel with the low levels of eNOS (p < 0.05). High glucose vessel treated with sulfasalazine showed low E_max value for contraction (p < 0.001) however, the E_max for relaxation was significantly high (p < 0.001) when compared to high glucose group. In the JNK group, E_max for contraction and relaxation was inhibited (p < 0.001) compared to sulfasalazine treated vessels. HO—1 enzyme levels were significantly low (p < 0.01) with sulfasalazine but higher with ERK inhibitor (p < 0.05).

Conclusion: High glucose induced endothelial dysfunction and sulfasalazine reduced damage in high glucose vessels by activating eNOS, antioxidant effect through HO-1 enzymes and particularly inducing Nrf2 via the ERK and JNK pathways.

• heart failure with preserved ejection fraction
• pathophysiology
• therapies
• type 2 diabetes mellitus

• Diabetes Mellitus, Type 2/complications
• Diabetes Mellitus, Type 2/therapy
• Heart Failure/therapy
• Humans
• Risk Factors
• Stroke Volume/physiology

• National Natural Science Foundation of China
• Chinese Academy of Medical Sciences

• Advanced glycation end products
• Skin auto fluorescence
• Type 2 diabetes

• AGE-RAGE signalling
• Advanced glycation end products
• Atherosclerosis
• Inflammation
• RAGE receptors

• Atherosclerosis/metabolism
• Glycation End Products, Advanced/metabolism
• Humans
• Plaque, Atherosclerotic
• Receptor for Advanced Glycation End Products/metabolism
• Signal Transduction

Patients with chronic kidney disease (CKD) are more prone to oxidative stress and chronic inflammation, which may lead to an increase in the synthesis of advanced glycation end products (AGEs). Because AGEs are mostly removed by healthy kidneys, AGE accumulation is a result of both increased production and decreased kidney clearance. On the other hand, AGEs may potentially hasten decreasing kidney function in CKD patients, and are independently related to all-cause mortality. They are one of the non-traditional risk factors that play a significant role in the underlying processes that lead to excessive cardiovascular disease in CKD patients. When AGEs interact with their cell-bound receptor (RAGE), cell dysfunction is initiated by activating nuclear factor kappa-B (NF-κB), increasing the production and release of inflammatory cytokines. Alterations in the AGE-RAGE system have been related to the development of several chronic kidney diseases. Soluble RAGE (sRAGE) is a decoy receptor that suppresses membrane-bound RAGE activation and AGE-RAGE-related toxicity. sRAGE, and more specifically, the AGE/sRAGE ratio, may be promising tools for predicting the prognosis of kidney diseases. In the present review, we discuss the potential role of AGEs and sRAGE as biomarkers in different kidney pathologies.

• advanced glycation end products (AGEs)
• chronic kidney disease (CKD)
• soluble receptor for AGEs (sRAGE)

• Biomarkers
• Cardiovascular Diseases
• Glycation End Products, Advanced
• Humans
• Inflammation
• Receptor for Advanced Glycation End Products
• Renal Insufficiency, Chronic

• diabetes
• diabetic cardiomyopathy
• endothelial dysfunction
• metabolism
• oxidative stress

• Diabetes Mellitus/pathology
• Diabetic Cardiomyopathies/etiology
• Diabetic Cardiomyopathies/metabolism
• Heart Failure/complications
• Humans
• Hyperglycemia/complications
• Myocardium/pathology
• Oxidative Stress/physiology

• National Natural Science Foundation of China

The accumulation of advanced glycation end products (AGEs) have been implicated in the development and progression of diabetic vasculopathy. However, the role of profilin-1 as a multifunctional actin-binding protein in AGEs-induced atherosclerosis (AS) is largely unknown.

To explore the potential role of profilin-1 in the pathogenesis of AS induced by AGEs, particularly in relation to the Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) signaling pathway.

Eighty-nine individuals undergoing coronary angiography were enrolled in the study. Plasma cytokine levels were detected using ELISA kits. Rat aortic vascular smooth muscle cells (RASMCs) were incubated with different compounds for different times. Cell proliferation was determined by performing the MTT assay and EdU staining. An AGEs-induced vascular remodeling model was established in rats and histological and immunohistochemical analyses were performed. The mRNA and protein levels were detected using real-time PCR and Western blot analysis, respectively. In vivo, shRNA transfection was performed to verify the role of profilin-1 in AGEs-induced proatherogenic mediator release and aortic remodeling. Statistical analyses were performed using SPSS 22.0 software.

Compared with the control group, plasma levels of profilin-1 and receptor for AGEs (RAGE) were significantly increased in patients with coronary artery disease, especially in those complicated with diabetes mellitus (P < 0.01). The levels of profilin-1 were positively correlated with the levels of RAGE (P < 0.01); additionally, the levels of both molecules were positively associated with the degree of coronary artery stenosis (P < 0.01). In vivo, tail vein injections of AGEs induced the release of proatherogenic mediators, such as asymmetric dimethylarginine, intercellular adhesion molecule-1, and the N-terminus of procollagen III peptide, concomitant with apparent aortic morphological changes and significantly upregulated expression of the profilin-1 mRNA and protein in the thoracic aorta (P < 0.05 or P < 0.01). Downregulation of profilin-1 expression with an shRNA significantly attenuated AGEs-induced proatherogenic mediator release (P < 0.05) and aortic remodeling. In vitro, incubation of vascular smooth muscle cells (VSMCs) with AGEs significantly promoted cell proliferation and upregulated the expression of the profilin-1 mRNA and protein (P < 0.05). AGEs (200 μg/mL, 24 h) significantly upregulated the expression of the STAT3 mRNA and protein and JAK2 protein, which was blocked by a JAK2 inhibitor (T3042-1) and/or STAT3 inhibitor (T6308-1) (P < 0.05). In addition, pretreatment with T3042-1 or T6308-1 significantly inhibited AGEs-induced RASMC proliferation (P < 0.05).

AGEs induce proatherogenic events such as VSMC proliferation, proatherogenic mediator release, and vascular remodeling, changes that can be attenuated by silencing profilin-1 expression. These results suggest a crucial role for profilin-1 in AGEs-induced vasculopathy.

• Advanced glycation end products
• Profilin-1
• Diabetic macroangiopathy
• Atherosclerosis
• Vascular remodeling
• Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway

• RAGE
• collateral vessels
• satellite cells

Diabetes mellitus is estimated to affect up to 700 million people by the year 2045, contributing to an immense health and economic burden. People living with diabetes have a higher risk of developing numerous debilitating vascular complications, leading to an increased need for medical care, a reduced quality of life and increased risk of early death. Current treatments are not satisfactory for many patients who suffer from impaired angiogenesis in response to ischaemia, increasing their risk of ischaemic cardiovascular conditions. These vascular pathologies are characterised by endothelial dysfunction and abnormal angiogenesis, amongst a host of impaired signaling pathways. Therapeutic stimulation of angiogenesis holds promise for the treatment of diabetic vascular complications that stem from impaired ischaemic responses. However, despite significant effort and research, there are no established therapies that directly stimulate angiogenesis to improve ischaemic complications such as ischaemic heart disease and peripheral artery disease, highlighting the immense unmet need. However, despite significant effort and research, there are no established therapies that directly stimulate angiogenesis in a clinical setting, highlighting the immense unmet need. MicroRNAs (miRNAs) are emerging as powerful targets for multifaceted diseases including diabetes and cardiovascular disease. This review highlights the potential role of microRNAs as therapeutic targets for rescuing diabetes-impaired angiogenesis, with a specific focus on miR-181c, which we have previously identified as an important angiogenic regulator. Here we summarise the pathways currently known to be regulated by miR-181c, which include the classical angiogenesis pathways that are dysregulated in diabetes, mitochondrial function and axonal guidance, and describe how these relate both directly and indirectly to angiogenesis. The pleiotropic actions of miR-181c across multiple key angiogenic signaling pathways and critical cellular processes highlight its therapeutic potential as a novel target for treating diabetic vascular complications.

• apoptosis
• axon guidance
• endothelial dysfunction
• hypoxia
• migration
• mitochondrial function
• proliferation

• Acute coronary syndrome
• Carbonyl stress
• Methylglyoxal
• Type 2 diabetes mellitus

The apolipoprotein E (ApoE) gene polymorphism has been found to influence plasma lipid concentration, and its correlation with peripheral arterial disease (PAD) has been investigated. However, it is unclear whether ApoE is associated with PAD in Chinese type 2 diabetes mellitus (T2DM) patients. Therefore, our study is aimed at investigating the relationship between the ApoE gene polymorphism and PAD in Chinese T2DM patients.

A total of 192 T2DM patients were divided into two groups: T2DM and T2DM with PAD. The clinical and biochemical parameters were obtained. Polymerase chain reaction was used to identify the genotypes of ApoE. The multivariable logistic regression analysis was used to identify the possible risk factor for PAD.

There were no significant differences in the genotype and allele frequencies of ApoE between the T2DM and T2DM with PAD groups. However, the T2DM with PAD group tended to have more ε4/ε4/

These results demonstrated that there was no evidence of a relationship between ApoE and PAD.

Vitamin D deficiency can lead to the increased severity and prevalence of metabolic disorders. However, the relationship between levels of 25-hydroxyvitamin D (25(OH)D) and peripheral arterial disease (PAD) is controversial. Therefore, the purpose of our study was to explore the relationship between 25(OH)D levels and PAD in middle-aged and elderly type 2 diabetes mellitus (T2DM) patients in China.

In this study, a total of 183 patients with T2DM were enrolled and categorized into groups with or without PAD. Clinical and biochemical parameters were assessed, and a Pearson analysis was used to identify a possible association between levels of 25(OH)D and glycated hemoglobin (HbA1c). Some biochemical parameters were also assessed in the T2DM patients with PAD according to vitamin D status. Interactions were also explored among HbA1c control, 25(OH)D levels, and PAD. The possible risk factors for PAD were measured by multivariable logistic regression analyses.

Firstly, the parameters including age, HbA1c, and disease duration between T2DM and T2DM+PAD groups showed significantly different. In addition, the frequency of smoking in the group of T2DM patients was significantly less than that in the T2DM patients with the PAD group, while the frequency of well-controlled HbA1c in the patients with T2DM was significantly higher. There is a trend that the levels of 25(OH)D and HbA1c are correlated, but no interactions among vitamin D deficiency, HbA1c control, and PAD were found. However, HbA1c significantly differed between groups with vitamin D deficiency and insufficiency in the T2DM patients with PAD. According to the multivariate logistic regression analyses, the PAD risk factors of T2DM patients were family history of diabetes, smoking, age, disease duration, HbA1c, and LDL.

The findings demonstrate that the deficiency of vitamin D level is not related to PAD, but HbA1c may be linked to the presence of PAD in middle-aged and elderly patients with T2DM in China.

Evidence exists regarding the association between advanced glycation end products and different cardiovascular disease subclinical processes, such as arterial stiffness and atherosclerosis. With this systematic review and meta-analysis, we aimed to provide a synthesis of the evidence regarding the association of arterial stiffness measured by pulse wave velocity and atherosclerosis measured by carotid intima media thickness with skin autofluorescence. A systematic search was performed using: MEDLINE (PubMed), SCOPUS, and Web of Science, until 30 March 2020. Cross-sectional studies or baseline data from prospective longitudinal studies were considered. The DerSimonian and Laird method was used to calculate the pooled estimates of correlation coefficients and the corresponding 95% confidence intervals (CI) for the association of pulse wave velocity and carotid intima media thickness with skin autofluorescence. Twenty-five studies were included in the systematic review and meta-analysis, including 6306 subjects. The pooled correlation coefficient was 0.25 (95% CI: 0.18, 0.31) for pulse wave velocity and skin autofluorescence, and 0.31 (95% CI: 0.25, 0.38) for carotid intima media thickness and skin autofluorescence. This systematic review and meta-analysis provide a synthesis of the evidence showing a positive weak association of pulse wave velocity and carotid intima media thickness with skin autofluorescence.

• advanced glycation end products
• arterial stiffness
• cardiovascular disease
• carotid intima media thickness
• pulse wave velocity
• skin autofluorescence

• Ankle Brachial Index
• Biomarkers
• Carotid Intima-Media Thickness
• Cross-Sectional Studies
• Glycation End Products, Advanced/metabolism
• Humans
• Prospective Studies
• Pulse Wave Analysis
• Skin
• Vascular Diseases/diagnosis
• Vascular Stiffness

• advanced glycation end products
• cardiovascular diseases
• diet

• Cardiovascular Diseases/epidemiology
• Cardiovascular Diseases/metabolism
• Cardiovascular Diseases/prevention & control
• Diet/adverse effects
• Diet, Healthy
• Diet, Mediterranean
• Glycation End Products, Advanced/metabolism
• Humans
• Protective Factors
• Receptor for Advanced Glycation End Products/metabolism
• Risk Assessment
• Risk Factors
• Risk Reduction Behavior
• Signal Transduction

Growing evidence supports the role of advanced glycation end products (AGEs) in the development of diabetic vascular complications and cardiovascular diseases (CVDs). We have shown that high-molecular-weight AGEs (HMW-AGEs), present in our Western diet, impair cardiac function. Whether HMW-AGEs affect vascular function remains unknown. In this study, we aimed to investigate the impact of chronic HMW-AGEs exposure on vascular function and structure. Adult male Sprague Dawley rats were daily injected with HMW-AGEs or control solution for 6 weeks. HMW-AGEs animals showed intracardiac pressure overload, characterized by increased systolic and mean pressures. The contraction response to PE was increased in aortic rings from the HMW-AGEs group. Relaxation in response to ACh, but not SNP, was impaired by HMW-AGEs. This was associated with reduced plasma cyclic GMP levels. SOD restored ACh-induced relaxation of HMW-AGEs animals to control levels, accompanied by a reduced half-maximal effective dose (EC₅₀). Finally, collagen deposition and intima-media thickness of the aortic vessel wall were increased with HMW-AGEs. Our data demonstrate that chronic HMW-AGEs exposure causes adverse vascular remodelling. This is characterised by disturbed vasomotor function due to increased oxidative stress and structural changes in the aorta, suggesting an important contribution of HMW-AGEs in the development of CVDs.

• AGEs
• ARHGAP18
• Diabetic foot
• Endothelial cells
• RhoA/ROCK signaling pathway

Endothelial dysfunction and intima-media thickness of common carotid arteries (IMT-CC) are considered subclinical markers of atherosclerotic cardiovascular disease (ASCVD). Advanced glycation end products (AGEs) are increased in type 2 diabetes mellitus (T2DM) patients, compared with non-diabetics, being implicated in micro- and macrovascular complications. Our aim was to compare serum AGEs levels and subclinical atherosclerotic markers between patients with established and newly diagnosed T2DM. Among 540 patients with T2DM and coronary heart disease from the CORDIOPREV study, 350 patients had established T2DM and 190 patients had newly diagnosed T2DM. Serum levels of AGEs (methylglyoxal (MG) and N-carboxymethyl lysine (CML)) and subclinical atherosclerotic markers (brachial flow-mediated vasodilation (FMD) and IMT-CC) were measured. AGEs levels (all p < 0.001) and IMT-CC (p = 0.025) were higher in patients with established vs. newly diagnosed T2DM, whereas FMD did not differ between the two groups. Patients with established T2DM and severe endothelial dysfunction (i.e., FMD < 2%) had higher serum MG levels, IMT-CC, HOMA-IR and fasting insulin levels than those with newly diagnosed T2DM and non-severe endothelial dysfunction (i.e., FMD ≥ 2%) (all p < 0.05). Serum CML levels were greater in patients with established vs. newly diagnosed T2DM, regardless of endothelial dysfunction severity. Serum AGEs levels and IMT-CC were significantly higher in patients with established vs. newly diagnosed T2DM, highlighting the progressively increased risk of ASCVD in the course of T2DM. Establishing therapeutic strategies to reduce AGEs production and delay the onset of cardiovascular complications in newly diagnosed T2DM patients or minimize ASCVD risk in established T2DM patients is needed.

• CORDIOPREV
• N-carboxymethyl lysine
• advanced glycation end products
• endothelial dysfunction
• flow-mediated vasodilation
• intima-media thickness of common carotid arteries
• methylglyoxal
• type 2 diabetes mellitus

• Diabetes mellitus
• anticoagulation
• antiplatelets
• cardiovascular disease
• clopidogrel
• myocardial infarction

• Anticoagulants/therapeutic use
• Diabetes Mellitus/drug therapy
• Drug Therapy, Combination
• Fibrinolytic Agents/therapeutic use
• Humans
• Platelet Aggregation Inhibitors/therapeutic use
• Secondary Prevention

• Advanced glycation end products
• Carotid arteries
• Contraction
• Thromboxane-prostanoid receptor
• Uridine diphosphate
• Vascular smooth muscle

• Angiogenesis
• Diabetes
• Inflammation
• Proliferative retinopathy
• VEGF
• Vitreous

• advanced glycation end products
• catalpol
• endothelial dysfunction
• nitric oxide

• Advanced glycation end products (AGEs)
• Coronary artery disease
• Endothelium
• Platelets
• RAGE
• Stent restenosis

• Animals
• Coronary Artery Disease/etiology
• Coronary Artery Disease/genetics
• Coronary Artery Disease/metabolism
• Coronary Artery Disease/therapy
• Glycation End Products, Advanced/metabolism
• Glycation End Products, Advanced/physiology
• Humans
• Molecular Targeted Therapy/methods
• Myocytes, Smooth Muscle/metabolism
• Oxidative Stress/physiology
• Receptor for Advanced Glycation End Products/metabolism
• Receptor for Advanced Glycation End Products/physiology
• Signal Transduction/physiology

• cardiomyopathy
• diabetes
• diabetic cardiovascular complications
• endothelium
• heart failure
• metabolism
• vascular

• Animals
• Diabetes Complications/physiopathology
• Diabetes Mellitus, Type 1/complications
• Diabetes Mellitus, Type 1/physiopathology
• Diabetes Mellitus, Type 2/complications
• Diabetes Mellitus, Type 2/physiopathology
• Diabetic Angiopathies/etiology
• Diabetic Angiopathies/physiopathology
• Diabetic Cardiomyopathies/etiology
• Diabetic Cardiomyopathies/physiopathology
• Endothelium, Vascular/physiopathology
• Glycolysis/physiology
• Human Umbilical Vein Endothelial Cells
• Humans
• Hyperglycemia/complications
• Mitochondria/physiology
• Nitric Oxide/antagonists & inhibitors
• Oxidative Stress/physiology

• P30 DK020595 NIDDK NIH HHS

• AGEs
• PAD
• RAGE
• atherosclerosis

• mechanosensor
• passive leg movement
• vascular function

• Krüppel‐like factor 2
• advanced glycosylation end products
• chronic kidney disease
• endothelial dysfunction
• uremia

• Animals
• Blood Proteins/metabolism
• Cell Survival/drug effects
• Cells, Cultured
• Disease Models, Animal
• Down-Regulation
• Glycation End Products, Advanced/toxicity
• Human Umbilical Vein Endothelial Cells/drug effects
• Human Umbilical Vein Endothelial Cells/metabolism
• Human Umbilical Vein Endothelial Cells/pathology
• Humans
• Kruppel-Like Transcription Factors/metabolism
• Protein Binding
• Reactive Oxygen Species/metabolism
• Receptor for Advanced Glycation End Products/agonists
• Receptor for Advanced Glycation End Products/metabolism
• Renal Dialysis
• Renal Insufficiency, Chronic/blood
• Renal Insufficiency, Chronic/therapy
• Serum Albumin, Bovine/toxicity
• Sus scrofa
• Transcription Factor RelA/metabolism
• Uremia/blood
• Uremia/therapy

• K08 HL121131 NHLBI NIH HHS
• R00 HL116786 NHLBI NIH HHS
• T32 GM063483 NIGMS NIH HHS
• I01 BX002390 BLRD VA
• K99 HL116786 NHLBI NIH HHS

• diabetes
• glycation
• myo-inositol oxygenase
• reactive oxygen species

Cardiac injury, including hypertrophy and fibrosis, induced by advanced glycation end products (AGEs) has an important function in the onset and development of diabetic cardiomyopathy. Profilin-1, a ubiquitously expressed and multifunctional actin-binding protein, has been reported to be an important mediator in cardiac hypertrophy and fibrosis. However, whether profilin-1 is involved in AGE-induced cardiac hypertrophy and fibrosis remains to be determined. Therefore, the present study aimed to investigate the function of profilin-1 in cardiac injury induced by AGEs. The model of cardiac injury was established by chronic tail vein injection of AGEs (50 mg/kg/day for 8 weeks) in Sprague-Dawley rats. Rats were randomly assigned to control, AGEs, AGEs + profilin-1 shRNA adenovirus vectors (AGEs + S)or AGEs + control adenovirus vectors (AGEs + V) groups. Profilin-1 shRNA adenovirus vectors were injected via the tail vein to knockdown profilin-1 expression at a dose of 3×10⁹ plaque forming units every 4 weeks. Echocardiography was performed to measure cardiac contractile function. Cardiac tissues were stained with Masson's trichrome stain to evaluate ventricular remodeling. The serum levels of procollagen type III N-terminal peptide were detected by ELISA. The expression of profilin-1, receptor for AGEs (RAGE), Rho, p65, atrial natriuretic peptide, β-myosin heavy chain, matrix metalloproteinase (MMP)-2 and MMP-9 were determined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and/or western blot analysis and immunohistochemistry staining. The results demonstrated that chronic injection of exogenous AGEs led to cardiac dysfunction, hypertrophy and fibrosis, as determined by echocardiography, Masson trichrome staining and the expression of associated genes. The expression of profilin-1 was markedly increased in heart tissue at the mRNA and protein level following AGE administration, as determined by RT-qPCR and western blotting, which was further confirmed by immunohistochemistry staining. Furthermore, the expression of RAGE, Rho and p65 was also increased at the protein level. Notably, knockdown of profilin-1 expression ameliorated AGE-induced cardiac injury and reduced the expression of RAGE, Rho and p65. These results indicate an important role for profilin-1 in AGE-induced cardiac injury, which may provide a novel therapeutic target for patients with diabetic heart failure.