scholarly journals The Role of a Selective P2Y6 Receptor Antagonist, MRS2578, on the Formation of Angiotensin II-Induced Abdominal Aortic Aneurysms

2020 ◽  
Vol 2020 ◽  
pp. 1-15 ◽  
Author(s):  
Xiao Du ◽  
Shilan Zhang ◽  
Qunyan Xiang ◽  
Jingyuan Chen ◽  
Feng Tian ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Aortic Aneurysms ◽  
Control Group ◽  
Placebo Control ◽  
High Dose ◽  
Ang Ii ◽  
Abdominal Aortic ◽  
Significant Difference ◽  
Expression And Activity

Objective. The P2Y6 receptor has been shown to be involved in many cardiovascular diseases, including hypertension and atherosclerosis. The study is aimed at exploring the role of the P2Y6 receptor in Ang II-induced abdominal aortic aneurysm (AAA) formation in apolipoprotein E-deficient (apoE-/-) mice by using its selective antagonist. Methods. Male apoE-/- mice were fed with high-fat diet and infused with angiotensin (Ang) II (1000 ng/kg/min) for 4 weeks to induce AAA or saline as controls. Mice were divided into four groups: normal saline (NS, placebo control) group (n=8), Ang II+vehicle (Ang II) group (n=14), Ang II-low dose MRS2578 (Ang II+MRS-16 mg) group (n=14), and Ang II-high dose MRS2578 (Ang II+MRS-32 mg) group (n=14). Daily intraperitoneal injection with vehicle or MRS2578 was pretreated one week before Ang II infusion. On postoperative day 10, aorta imaging of each group was taken by ultrasonography. After 4 weeks of Ang II infusion, the excised aortas were processed for diameter measurement and quantification of aneurysm severity and tissue characteristics; the blood samples were collected for measurement of the lipid profile and levels of cytokines. Verhoeff’s Van Gieson (EVG) staining and immunochemistry staining were performed to evaluate disruption of the extracellular matrix (ECM) and infiltration of macrophages. Expression and activity of matrix metalloproteinases (MMPs) was measured by gelatin zymography. Results. Treatment with MRS2578 made no significant difference in AAA formation, and maximal aortic diameter yet caused higher AAA rupture-induced mortality from 7% (Ang II) to 21.4% (Ang II+MRS-16 mg) or 42.9% (Ang II+MRS-32 mg), respectively (p<0.05). Consistently, the severity of aneurysm tended to be more deteriorated in MRS2578-treated groups, especially the high-dosage group. The ratios of type III and IV aneurysm were much higher in the MRS2578-coadministered groups (p<0.05). Furthermore, histological analyses showed that administration of MRS2578 significantly increased infiltration of macrophages, expression of monocyte chemotactic protein 1 (MCP-1) and vascular cell adhesion molecule-1 (VCAM-1), and activities of MMP-2 and MMP-9 followed by aggravating degradation elastin in vivo (p<0.05). However, the multiple effects of MRS2578 on the development of AAA are independent of changes in systolic blood pressure and lipid profiles. Conclusions. The present study demonstrated that administration of MRS2578 exacerbated the progression and rupture of experimental AAA through promoting proinflammatory response and MMP expression and activity, which indicated a crucial role of the P2Y6 receptor in AAA development. Clinical Relevance. Purinergic P2Y receptors have attracted much attention since the P2Y12 receptor antagonist had been successfully applied in clinical practice. Elucidating the underlying mechanisms of AAA and exploring potential therapeutic strategies are essential to prevent its progression and reduce the mortality rate.

Effects of long-term chloroquine administration on the natural history of aortic aneurysms in mice

2015 ◽  
Vol 93 (8) ◽  
pp. 641-648 ◽  
Author(s):  
Azza Ramadan ◽  
Mark D. Wheatcroft ◽  
Adrian Quan ◽  
Krishna K. Singh ◽  
Fina Lovren ◽  
...  
Keyword(s):  
Natural History ◽  
Thrombus Formation ◽  
Aortic Aneurysms ◽  
Ang Ii ◽  
Abdominal Aortic ◽  
Suprarenal Aorta ◽  
History Of ◽  
Categorical Distribution

Autophagy regulates cellular homeostasis and integrates the cellular pro-survival machinery. We investigated the role of autophagy in the natural history of murine abdominal aortic aneurysms (AAA). ApoE−/− mice were implanted with saline- or angiotensin II (Ang-II)-filled miniosmotic pumps then treated with either the autophagy inhibitor chloroquine (CQ; 50 mg·(kg body mass)–1·day–1, by intraperitoneal injection) or saline. Ang-II-elicited aneurysmal expansion of the suprarenal aorta coupled with thrombus formation were apparent 8 weeks later. CQ had no impact on the incidence (50% for Ang-II compared with 46.2% for Ang-II + CQ; P = NS) and categorical distribution of aneurysms. The markedly reduced survival rate observed with Ang-II (57.1% for Ang-II compared with 100% for saline; P < 0.05) was unaffected by CQ (61.5% for Ang-II + CQ; P = NS compared with Ang-II). CQ did not affect the mean maximum suprarenal aortic diameter (1.91 ± 0.19 mm for Ang-II compared with 1.97 ± 0.21 mm for Ang-II + CQ; P = NS). Elastin fragmentation, collagen accumulation, and smooth muscle attrition, which were higher in Ang-II-treated mice, were unaffected by CQ treatment. Long-term CQ administration does not affect the natural history and prognosis of experimental AAA, suggesting that global loss of autophagy is unlikely to be a causal factor in the development of aortic aneurysms. Manipulation of autophagy as a mechanism to reduce AAA may need re-evaluation.

Abstract 667: The Role of Aortic Wall-Nuclear Factor- kappa B (NF-kB) Signaling in Formation of Dissecting Aortic Aneurysms

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Talha Ijaz ◽  
Hong Sun ◽  
Adrian Recinos ◽  
Ronald G Tilton ◽  
Allan R Brasier
Keyword(s):  
Flow Cytometry ◽  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Aortic Wall ◽  
Aortic Rupture ◽  
Aortic Aneurysms ◽  
Tunel Staining ◽  
Abdominal Aortic ◽  
Significant Difference

Introduction: Abdominal aortic aneurysm is a devastating disease since it can lead to aortic rupture and instantaneous death. We previously demonstrated that IL-6 secreted from the aortic wall is necessary for the development of abdominal aortic aneurysm and dissection (AAD). Since IL-6 is a NF-kB/RelA dependant gene, we investigated the role of aortic wall- NF-kB/RelA signaling in the development of AAD. Methods and Results: To test the role of aortic wall-RelA, we utilized Cre-Lox technology to delete RelA from aortic cells. Tamoxifen-inducible, Col1a2-promoter driven Cre mice (Col1a2-Cre) were crossed with mT/mG Cre-reporter mice to determine which aortic cells undergo genetic recombination after Cre activation. Flow cytometry analysis of the aortic wall indicated that 88% of the genetically recombined cells were SMCs and 8% were fibroblasts. Next, RelA floxed (RelA f/f) mice, generated in our lab, were crossed with Col1a2-Cre mice. RelA f/f Cre+ and RelA f/f Cre- were stimulated with tamoxifen for 10 days to generate aortic-RelA deficient (Ao-RelA-/-) or wild-type (Ao-RelA+/+) transgenics. Flow cytometry, qRT-PCR, and immunohistochemistry analysis suggested a depletion of aortic-RelA greater than 60%. To test the role of Ao-RelA in AAD, Ao-RelA -/- (n= 20) and Ao-RelA +/+ (n=14) mice were infused with angiotensin II for 7 days. Surprisingly, 20% of Ao-RelA-/- mice died from development of AAD and aortic rupture while no deaths were observed in Ao-RelA+/+ group. In addition, 40% of Ao-RelA-/- mice developed AAD compared to 14% of Ao-RelA+/+ mice. There was no significant difference in TUNEL staining or ERTR7+ fibroblast population between the two groups. Conclusion: Our studies suggest that aortic wall-RelA may be necessary for protection from AAD.

The Role of Serum Calprotectin as a New Marker in Abdominal Aortic Aneurysms – A Preliminary Report

2020 ◽  
Vol 21 ◽  
Author(s):  
Willy Hauzer ◽  
Stanisław Ferenc ◽  
Joanna Rosińczuk ◽  
Jan Gnus
Keyword(s):  
Healthy Subjects ◽  
Polyclonal Antibodies ◽  
Aortic Aneurysms ◽  
Control Group ◽  
Study Group ◽  
Abdominal Aortic ◽  
Peroxidase Enzyme ◽  
Calprotectin Level ◽  
Twofold Decrease

Background: Abdominal aortic aneurysm (AAA) remains a surgical challenge. There are many recognizable markers associated with the formation of AAA. Previous experiments carried out on animal models have shown a correlation between serum calprotectin and the occurrence of AAA. Objective: This study aimed to evaluate the level of calprotectin as a potential diagnostic biomarker in patients with diagnosed AAA. Method: The study group consisted of 75 patients aged 35–75 years who were assigned to two groups: a control group (n=43) of healthy subjects without AAA and a study group (n=32) of patients with a diagnosed AAA. The first calprotectin test was performed upon patient admission to the hospital, and the second control test was performed after three months. The concentration of calprotectin in plasma was determined using the immunoenzymatic method (ELISA) with the commercially available Assaypro Kit (AssayMax™ Human Calprotectin ELISA Kit), as well as the sandwich method with polyclonal antibodies to human calprotectin and peroxidase enzyme. Results & Discussion: Serum calprotectin levels in AAA patients were three times higher than in healthy subjects (p<0.05). A statistically significant a twofold decrease in calprotectin concentration was observed after AAA surgery in comparison with the control group (p<0.05). Conclusion: Calprotectin levels can be an important marker in the detection of AAA. In conclusion, AAA patients showed a threefold increase in serum calprotectin level and a twofold decrease in this marker after AAA surgery.

scholarly journals Tissue microRNA expression in aortic aneurysm dissection

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
A Goliopoulou ◽  
E Oikonomou ◽  
M Gazouli ◽  
N Koumalos ◽  
D Lymperiadis ◽  
...  
Keyword(s):  
Aortic Wall ◽  
Rna Extraction ◽  
Tissue Expression ◽  
Microrna Expression ◽  
Aortic Aneurysms ◽  
Control Group ◽  
Aortic Dilatation ◽  
Elisa Method ◽  
Significant Difference

Abstract Background Dissection and other complications of ascending aortic aneurysms are potentially life-threatening. Several factors may be implicated in aneurysm progression and dissection. The role of tissue microRNAs may be of interest. Purpose To examine how serum biomarkers and tissue expression of microRNAs are associated with thoracic aortic aneurysms and dissection. Methods We compared three groups of patients; 21 patients with aneurysm of the aortic root, ascending aorta or aortic arch undergoing scheduled repair, 11 patients with acute Stanford type A aortic dissection who underwent emergency surgery and 18 patients with normal aortic diameter undergoing other cardiac surgery (control group). Prior to surgery, peripheral blood samples were obtained from patients, to assess osteoprotegerin and adiponectin levels with the ELISA method. Tissue samples from ascending aortic wall were obtained from patients during surgery. Following appropriate storage and homogenization, tissue Matrix Metalloproteinases (MMPs) 2 and 9 were measured with the ELISA method, while tissue microRNAs 29 and 195 were measured using qrtPCR, after RNA extraction. Results There was no significant difference among control, aneurysm and dissection groups in terms of age (62±10 years vs 66±12 years vs 59±12 years, p=0.052), gender distribution (77.8% male vs 81% male vs 90% male, p=0.28) or BMI (28.51±2.92 kg/m2 vs 25.72±3.09 kg/m2 vs 27.02±3.2 kg/m2, p=0.76). There was also no difference among control, aneurysm and dissection groups regarding hypertension (72% vs 62% vs 73%, p=0.73), diabetes mellitus (22% vs 19% vs 36%, p=0.54), smoking (44% vs 29% vs 46%, p=0.09) or dyslipidemia (78% vs 43% vs 55%, p=0.08). The groups of control subjects, aneurysms and dissections did not differ in osteoprotegerin [44 (28, 52) pmol/l vs 31 (28, 37) pmol/l vs 45 (24, 71) pmol/l, p=0.17], adiponectin [6,65 (2,39, 9,79) μg/ml vs 5,28 (2,34, 6,98) μg/ml vs 4,13 (2,49, 7,52) μg/ml, p=0.43], tissue MMP2 [0.97 (0.42, 27.66) ng/ml vs 9.12 (1.72, 61.49) ng/ml vs 2.51 (0.22, 235.72) ng/ml, p=0.34] and tissue MMP9 levels [0.96 (0.29, 8.56) ng/ml vs 10.31 (1.18, 25.58) ng/ml vs 2.76 (0.63, 54.83) ng/ml, p=0.09] (Figure 1). Importantly, tissue expression of mir29 was 2.11-fold higher in the dissection group (p=0.001) and 2.99-fold higher in the aneurysm group (p&lt;0.001) compared to the control group. Tissue expression of mir195 was 2.72-fold higher in the dissection group (p&lt;0.001) and 2.00-fold lower in the aneurysm group (p=0.08) compared to the control group (Figure 2). Conclusions These findings highlight the role of epigenetic modifications through altered microRNA tissue expression in aortic wall synthesis, extracellular matrix degradation and progress of aneurysm formation and dissection. The exact role of microRNA expression in aortic dilatation and dissection, as well as their role as potential biomarkers, merit further validation. FUNDunding Acknowledgement Type of funding sources: None. Figure 1 Figure 2

scholarly journals Roles and functions of exosomal miRNA in abdominal aortic aneurysm

2020 ◽  
Author(s):  
YuBo Zhao ◽  
Shuwei Wan ◽  
Chuang Li ◽  
Yaming Guo ◽  
Gaopo Cai ◽  
...  
Keyword(s):  
Mapk Pathway ◽  
Aortic Aneurysms ◽  
Functional Enrichment ◽  
Mirna Sequence ◽  
Control Group ◽  
Abdominal Aortic ◽  
Exosomal Mirnas ◽  
Significant Difference ◽  
Healthy Control ◽  
Experimental Group

Abstract Background and objective: abdominal aortic aneurysms（AAAs）are the permanent dilatation of the abdominal aorta, ruptured AAA is a serious threat to the patient's life. It’s hardly known about exosomal miRNAs in AAA. The main purpose of this article is to screen miRNAs which differentially expressed in exosomes from normal people and patients with AAA, and to understand the mechanism of work.Material and methods: The plasma of healthy control group and patients with AAA were collected, and the RNAs from exosomes was isolated and sequenced. The mature miRNA sequence of miRBase 21 database was used to identify the known type and expression of miRNAs. DEGseq software was used to analyze the types of miRNAs with significant difference between the experimental group and the control group ( P ＜ 0.05, | log 2 (FoldChange) | ≥ 1 ). The targets of miRNAs were detected by miRTarBase, miRDB, TargetScan and miRWalk software. Targets were analyzed based on Kyoto encyclopedia of genes and genomes（ KEGG ）biological pathway and gene ontology（ GO ）functional enrichment analysis. Conclusion: miRNAs in exosomes regulate in the progress of AAA by activating PI3K-Akt/mTOR and MAPK pathway, and its mechanism needs more research. Background and objective: abdominal aortic aneurysms（AAAs）are the permanent dilatation of the abdominal aorta, ruptured AAA is a serious threat to the patient's life. It’s hardly known about exosomal miRNAs in AAA. The main purpose of this article is to screen miRNAs which differentially expressed in exosomes from normal people and patients with AAA, and to understand the mechanism of work. Material and methods: The plasma of healthy control group and patients with AAA were collected, and the RNAs from exosomes was isolated and sequenced. The mature miRNA sequence of miRBase 21 database was used to identify the known type and expression of miRNAs. DEGseq software was used to analyze the types of miRNAs with significant difference between the experimental group and the control group ( P ＜ 0.05, | log 2 (FoldChange) | ≥ 1 ). The targets of miRNAs were detected by miRTarBase, miRDB, TargetScan and miRWalk software. Targets were analyzed based on Kyoto encyclopedia of genes and genomes（ KEGG ）biological pathway and gene ontology（ GO ）functional enrichment analysis.Conclusion: miRNAs in exosomes regulate in the progress of AAA by activating PI3K-Akt/mTOR and MAPK pathway, and its mechanism needs more research.

Regulation of jejunal sodium and water absorption by angiotensin subtype receptors

1998 ◽  
Vol 275 (2) ◽  
pp. R515-R523 ◽  
Author(s):  
Xiao-Hong Jin ◽  
Zhi-Qin Wang ◽  
Helmy M. Siragy ◽  
Richard L. Guerrant ◽  
Robert M. Carey
Keyword(s):  
Water Absorption ◽  
Receptor Antagonist ◽  
Low Dose ◽  
Fluid Transport ◽  
Sodium Intake ◽  
High Dose ◽  
Ang Ii ◽  
Fluid Absorption ◽  
Dose Dependent Increase

The purpose of this study was to determine the precise role of angiotensin subtype-1 (AT1) and -2 (AT2) receptors and the mechanisms by which they act to alter fluid transport in the rat jejunum. In rats on normal sodium intake, ANG II at low dose stimulated net jejunal fluid absorption, whereas at a high dose the peptide inhibited absorption. Low-dose ANG II-stimulated fluid absorption was blocked completely by the specific AT2receptor antagonist PD-123319 (PD) but was unchanged by the AT1receptor antagonist losartan (Los). The AT2receptor agonist CGP-42112A, caused an inversely dose-dependent increase in fluid absorption, which also was totally prevented by PD but was unaltered by Los. Conversely, high-dose ANG II inhibition of absorption was blocked by Los but not by PD. In animals receiving normal sodium intake, neither Los nor PD alone altered fluid absorption. In sodium-restricted animals, however, Los alone increased absorption and PD alone inhibited absorption. In rats on normal sodium intake, low-dose ANG II increased jejunal interstitial and luminal (loop) fluid concentrations of cGMP. These increases in cGMP were blocked with PD but not with Los. 8-Bromoguanosine-3′,5′-cyclic monophosphate administered via the mesenteric artery or the submucosal interstitial space markedly increased absorption, but it inhibited absorption when administered into the loop. High-dose ANG II decreased jejunal interstitial and loop fluid cAMP and increased PGE2. The increase in PGE2was blocked by Los but not by PD. The data demonstrate that ANG II mediates jejunal sodium and water absorption by an action at the AT2receptor involving cGMP formation. The data also show that ANG II inhibits absorption via the AT1receptor by a mechanism that is both negatively coupled to cAMP and increases jejunal PGE2production.

scholarly journals Reduced Nhe1 (Na + -H + Exchanger-1) Function Protects ApoE-Deficient Mice From Ang II (Angiotensin II)–Induced Abdominal Aortic Aneurysms

Hypertension ◽  
2020 ◽  
Vol 76 (1) ◽  
pp. 87-100
Author(s):  
Cong-Lin Liu ◽  
Xin Liu ◽  
Yunzhe Wang ◽  
Zhiyong Deng ◽  
Tianxiao Liu ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Cell Apoptosis ◽  
Near Infrared ◽  
Gelatin Zymography ◽  
Aortic Aneurysms ◽  
Ang Ii ◽  
Abdominal Aortic ◽  
Ige Mediated ◽  
Human And Mouse

IgE-mediated activation of Nhe1 (Na + -H + exchanger-1) induces aortic cell extracellular acidification and promotes cell apoptosis. A pH-sensitive probe pHrodo identified acidic regions at positions of macrophage accumulation, IgE expression, and cell apoptosis in human and mouse abdominal aortic aneurysm (AAA) lesions. Ang II (angiotensin II)–induced AAA in Nhe1-insufficient Apoe −/− Nhe1 +/− mice and Apoe −/− Nhe1 +/+ littermates tested Nhe1 activity in experimental AAA, because Nhe1 −/− mice develop ataxia and epileptic-like seizures and die early. Nhe1 insufficiency reduced AAA incidence and size, lesion macrophage and T-cell accumulation, collagen deposition, elastin fragmentation, cell apoptosis, smooth muscle cell loss, and MMP (matrix metalloproteinase) activity. Nhe1 insufficiency also reduced blood pressure and the plasma apoptosis marker TCTP (translationally controlled tumor protein) but did not affect plasma IgE. While pHrodo localized the acidic regions to macrophage clusters, IgE expression, and cell apoptosis in AAA lesions from Apoe −/− Nhe1 +/+ mice, such acidic areas were much smaller in lesions from Apoe −/− Nhe1 +/− mice. Nhe1-FcεR1 colocalization in macrophages from AAA lesions support a role of IgE-mediated Nhe1 activation. Gelatin zymography, immunoblot, and real-time polymerase chain reaction analyses demonstrated that Nhe1 insufficiency reduced the MMP activity, cysteinyl cathepsin expression, IgE-induced apoptosis, and NF-κB activation in macrophages and blocked IgE-induced adhesion molecule expression in endothelial cells. A near-infrared fluorescent probe (LS662) together with fluorescence reflectance imaging of intact aortas showed reduced acidity in AAA lesions from Nhe-1-insufficient mice. This study revealed extracellular acidity at regions rich in macrophages, IgE expression, and cell apoptosis in human and mouse AAA lesions and established a direct role of Nhe1 in AAA pathogenesis.

scholarly journals Do Hernias Contribute to Increased Severity of Aneurysmal Disease among Abdominal Aortic Aneurysm Patients?

Aorta ◽  
2021 ◽  
Author(s):  
Irene Hinterseher ◽  
Milena Miszczuk ◽  
Florian Corvinus ◽  
Carolin Zimmermann ◽  
Mariana Estrelinha ◽  
...  
Keyword(s):  
Univariate Analysis ◽  
Aortic Aneurysms ◽  
Control Group ◽  
Exact Test ◽  
Group 4 ◽  
Inguinal Hernias ◽  
Abdominal Aortic ◽  
Significant Difference ◽  
High Prevalence ◽  
Chi Squared

Abstract Background Connective tissue disorders could contribute to the pathogenesis of both abdominal aortic aneurysms (AAA) and hernias. We tested the hypothesis that hernias in AAA patients contribute to increased severity of the aneurysmal disease. Methods A questionnaire was used to collect information from 195 AAA patients divided into four groups: (1) survivors (n = 22) of ruptured AAA, (2) patients (n = 90) after elective open repair, (3) patients (n = 43) after elective endovascular repair (EVAR), and (4) patients (n = 40) under surveillance of AAA. The control group consisted of 100 patients without AAA whose abdominal computed tomography (CT) scans were examined for the presence of hernias. Mann–Whitney U-test, Chi-squared (χ 2) test, or Fisher's exact test (as appropriate) were used for statistical analyses. Multivariate logistic regression was used to control for potential confounding variables such as sex and age. Results The prevalence of inguinal hernias was significantly higher in the AAA than the control group (25 vs. 9%, p = 0.001) and did not differ between the AAA subgroups (9, 24, 35, and 23% in subgroups 1 through 4, respectively, p = 0.15) based on univariate analysis. The prevalence of inguinal hernias did not differ (p = 0.15) between the two open surgery groups (groups 1 and 2), or when comparing all three operative procedures as a combined group to group 4 (p = 0.73). The prevalences of incisional hernias were 18 and 24% for groups 1 and 2, respectively, with no significant difference (p = 0.39). Inguinal hernia demonstrated a significant association with AAA on multivariate analysis (p = 0.006; odds ratio [OR] = 4.00; 95% confidence interval [CI] = 1.49–10.66). Conclusions Our study confirms previous observations that patients with AAA have a high prevalence of hernias. Our results suggest that hernias do not contribute to increased severity of the aneurysmal disease.

Effectiveness Of Toilet Training Education On Mother's Behavior And Toddler Age Toilet Training Ability (18-36 Months)

2020 ◽  
Vol 5 (2) ◽  
pp. 49-55
Author(s):  
Hafiko Andresni ◽  
Zahtamal Zahtamal ◽  
Winda Septiani ◽  
Mitra Mitra ◽  
Lita Lita
Keyword(s):  
Sampling Technique ◽  
T Test ◽  
The Body ◽  
Toilet Training ◽  
Wilcoxon Test ◽  
Control Group ◽  
Maternal Knowledge ◽  
Control Group Design ◽  
Significant Difference

ABSTRACT Toilet training is an effort to train children to be able to control and urinate (BAK) and defecate (BAB). Toilet training is one of the main tasks of children at toddler age. Toilet training is one of the main tasks of children in toddler age which is very important to be done to create independence in children in controlling BAK and BAB and children know the parts of the body and their functions. Data in 2012 shows that ± 60% of parents do not teach toilet training to children from an early age. The aim of the study was to find out the effectiveness of toilet training education on maternal behavior and toilet skills in toddler age training (18-36 months). The study was conducted in July-August 2018. This type of quantitative research used the design of the Quasy pretest and posttest experiment with non-equivalent control group design. Samples were 36 mothers and 36 children with purposive sampling technique. Data analysis used Paired t test, Wilcoxon test, Man-Whitney test an Independent t test. The results showed that toilet training education through lecture methods, modules and maze games was more effective than toilet training education through lecture and leaflet methods on children's knowledge and abilities. Conversely, for the role of mothers in supervision there is no significant difference in effectiveness. Health education is recommended in health promotion programs to increase maternal knowledge, the role of mothers and the ability of toilet training children independently. Keywords: Toilet training, Lecture method, Module, Maze game, Leaflet, Knowledge, Role of mother, Children's ability.

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