Publications by authors named "Yingnan Dai"

8 Publications

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Ivabradine protects rats against myocardial infarction through reinforcing autophagy via inhibiting PI3K/AKT/mTOR/p70S6K pathway.

Bioengineered 2021 Dec;12(1):1826-1837

Department of Cardiology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, P.R. China.

Ivabradine (Iva), a heart rate reducing agent that specifically inhibits the pacemaker ionic current, has been demonstrated to be cardioprotective in many cardiovascular diseases. Autophagy is an evolutionarily conserved metabolic process that regulates cardiac homeostasis. This study is aimed to explore whether autophagy is functionally involved in the cardioprotective effect of Iva in a rat model of myocardial infarction (MI). We observed that Iva treatment (po, 10 mg/kg/day) showed significant recovery on the hemodynamics parameters in MI rats, including left ventricular systolic pressure, left ventricular end diastolic pressure, and maximal ascending/descending rate of left ventricular pressure. Also, Iva treatment dramatically decreased infarct size, inhibited myocardial apoptosis, and reduced the levels of pro-inflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 in MI rats. Moreover, Iva treatment enhanced autophagy and inhibited PI3K/AKT/mTOR/p70S6K pathway in MI rats. Simultaneously, we observed that autophagy enhancer rapamycin (ip, 10 mg/kg/day) showed similar cardioprotective effects with Iva. Furthermore, we observed that addition of autophagy inhibitor 3-methyladenine (ip, 10 mg/kg/day) counteracted the therapeutic effect of Iva, addressing that Iva attenuated post-MI cardiac injury by enhancing autophagy. In summary, these findings demonstrated that Iva attenuated MI in rats by enhancing autophagy, and PI3K/AKT/mTOR/p70S6K pathway might be involved in the process. Autophagy activation by Iva may be a potential therapeutic strategy for the treatment of MI.
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http://dx.doi.org/10.1080/21655979.2021.1925008DOI Listing
December 2021

Down-regulation of lncRNA KCNQ1OT1 protects against myocardial ischemia/reperfusion injury following acute myocardial infarction.

Biochem Biophys Res Commun 2017 09 2;491(4):1026-1033. Epub 2017 Aug 2.

Department of Cardiology, The First Affiliated Hospital of Medical College of Xi'AN JIAOTONG University, Xian, Shanxi 710061, China. Electronic address:

This study aimed to investigate the protective effects of long non-coding RNA KCNQ1OT1 against myocardial ischemia/reperfusion (I/R) injury following acute myocardial infarction, as well as its regulatory mechanism. We used the cardiac muscle H9c2 cells under condition of oxygen glucose deprivation followed by reperfusion (OGD/R) to induce myocardial I/R injury. Then H9C2 cells were transfected with si-NC, si-KCNQ1OT1, pc-NC, pc-KCNQ1OT1, si-AdipoR1 and si-AdipoR2, respectively. The myocardial cell viability and apoptosis were respectively detected. In addition, the expression levels of inflammatory factors, apoptosis-related proteins and p38 MAPK/NF-κB pathway-related proteins were detected. Besides, an inhibitor of p38 MAPK/NF-κB pathway SB203580 was used to treat cells to verify the relationship between KCNQ1OT1 and p38 MAPK/NF-κB pathway. The expression of KCNQ1OT1 was significantly up-regulated in OGD/R-induced myocardial H9C2 cells. The OGD/R-induced decreased cell viability and AdipoR1 expression could be reversed after suppression of KCNQ1OT1. In addition, suppression of KCNQ1OT1 reduced OGD/R-induced increased expressions of TNF-α, IL-6 and IL-1β and OGD/R-induced increased cell apoptosis, which were reversed after knockdown of AdipoR1. Besides, suppression of KCNQ1OT1 significantly down-regulated the OGD/R-induced increased expression of p-p38 and p-NF-κB, which were also reversed after knockdown of AdipoR1. Moreover, SB203580, an inhibitor of p38 MAPK/NF-κB signal pathway, could further enhance the inhibitory effects of KCNQ1OT1 suppression on the expression of p-p38, TNF-α, IL-6, IL-1β and p-NF-κB in OGD/R-induced myocardial H9C2 cells. Suppression of KCNQ1OT1 may prevent myocardial I/R injury following acute myocardial infarction via regulating AdipoR1 and involving in p38 MAPK/NF-κB signal pathway.
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http://dx.doi.org/10.1016/j.bbrc.2017.08.005DOI Listing
September 2017

Association of folate metabolism gene polymorphisms and haplotype combination with pulmonary embolism risk in Chinese Han population.

Mamm Genome 2017 06 12;28(5-6):220-226. Epub 2017 May 12.

Department of Cardiology, The Fourth Affiliated Hospital of Harbin Medical University, Yiyuan Street No. 37 of Nangang District, Harbin City, 150001, Heilongjiang Province, China.

In this study, we aimed to investigate the association of four single nucleotide polymorphisms (SNPs) (MTHFR 677 C > T, MTHFR 1298 A > C, MTR 2756 A > G and MTRR 66 A > G), gene-gene interaction and haplotype combination with pulmonary embolism (PE) risk based on Chinese Han population. Logistic regression was performed to investigate association between four SNPs within folate metabolism gene and PE risk, and GMDR model was used to investigate the additional gene-gene interactions among the four SNPs. Logistic analysis showed that rs1801133 and rs1801131 in MTHFR gene were associated with increased PE risk in both additive and dominant models. The carriers with homozygous mutant of rs1801133 polymorphism and homozygous of rs1801131 were associated with increased PE risk, and ORs (95% CI) were 1.71(1.24-2.21) and 1.58 (1.24-2.01), respectively. We also found a significant gene-gene interaction between rs1801133 and rs1801131 on PE. Overall, the cross-validation consistency of this two-locus model was 10/10, and the testing accuracy was 60.72%, after adjusting for covariates. Haplotype containing the rs1801133- T and rs1801131- C alleles were associated with a statistically increased PE risk, OR (95% CI) = 2.68 (1.28-4.13), P < 0.001. We found that rs1801133 and rs1801131 within MTHFR gene, their interaction, and haplotype containing the rs1801133- T and rs1801131- C alleles were all associated with PE risk.
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http://dx.doi.org/10.1007/s00335-017-9692-9DOI Listing
June 2017

MicroRNA-9 inhibits high glucose-induced proliferation, differentiation and collagen accumulation of cardiac fibroblasts by down-regulation of TGFBR2.

Biosci Rep 2016 12 29;36(6). Epub 2016 Nov 29.

Vasculocardiology Department, The Fourth Affiliated Hospital of Harbin Medical University, Harbin 150001, China

To investigate the effects of miR-9 on high glucose (HG)-induced cardiac fibrosis in human cardiac fibroblasts (HCFs), and to establish the mechanism underlying these effects. HCFs were transfected with miR-9 inhibitor or mimic, and then treated with normal or HG. Cell viability and proliferation were detected by using the Cell Counting Kit-8 (CCK-8) assay and Brdu-ELISA assay. Cell differentiation and collagen accumulation of HCFs were detected by qRT-PCR and Western blot assays respectively. The mRNA and protein expressions of transforming growth factor-β receptor type II (TGFBR2) were determined by qRT-PCR and Western blotting. Up-regulation of miR-9 dramatically improved HG-induced increases in cell proliferation, differentiation and collagen accumulation of HCFs. Moreover, bioinformatics analysis predicted that the TGFBR2 was a potential target gene of miR-9 Luciferase reporter assay demonstrated that miR-9 could directly target TGFBR2. Inhibition of TGFBR2 had the similar effect as miR-9 overexpression. Down-regulation of TGFBR2 in HCFs transfected with miR-9 inhibitor partially reversed the protective effect of miR-9 overexpression on HG-induced cardiac fibrosis in HCFs. Up-regulation of miR-9 ameliorates HG-induced proliferation, differentiation and collagen accumulation of HCFs by down-regulation of TGFBR2. These results provide further evidence for protective effect of miR-9 overexpression on HG-induced cardiac fibrosis.
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http://dx.doi.org/10.1042/BSR20160346DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5293584PMC
December 2016

Resveratrol lowers blood pressure in spontaneously hypertensive rats via calcium-dependent endothelial NO production.

Clin Exp Hypertens 2016 28;38(3):287-93. Epub 2016 Mar 28.

a Department of Cardiology , The First Affiliated Hospital of Medical College, Xi'an Jiao Tong University , Xi'an , China.

Objective: Resveratrol, a polyphenol of natural compounds, has beneficial cardiovascular effects, many of which are mediated by nitric oxide (NO). Resveratrol increases intracellular calcium and activates AMP-activated protein kinase (AMPK), all of which could increase NO production. We hypothesized that resveratrol via a calcium-dependent NO production lowers blood pressure (BP) in spontaneously hypertensive rats (SHR).

Methods: Acetylcholine (Ach)-induced endothelium-dependent relaxations in rat aortas were examined by organ chamber. Blood pressures were determined by radiotelemetry methods.

Results: Incubation of isolated aortas from SHR with resveratrol dramatically improved vasorelaxation induced by Ach. Preincubation of aortas with endothelial NO synthase (eNOS) inhibitor or calcium chelant blunted the effects of resveratrol on Ach-induced relaxation, as wells as NO production and eNOS phosphorylation. In animal studies, administration of resveratrol significantly lowered systemic BP in SHR.

Conclusion: Resveratrol increases endothelial NO production to improve endothelial dysfunction and lowers BP in hypertensive rats, which depends on calcium-eNOS activation.
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http://dx.doi.org/10.3109/10641963.2015.1089882DOI Listing
December 2016

Neck circumference and future cardiovascular events in a high-risk population--A prospective cohort study.

Lipids Health Dis 2016 Mar 5;15:46. Epub 2016 Mar 5.

The Fourth Affiliated Hospital of Harbin Medical University, 37 Yiyuan Street, Habin, 150001, China.

Background: The distribution of adipose tissue has been evaluated in relation to cardiovascular risk factors and biochemical components of the metabolic syndrome. Neck circumference (NC) has been shown to have a strong relationship with cardiovascular disease (CVD) and may be a novel indicator of CVD. The aim of this study was to compare the incidence of CVD events in cohorts with different NC distributions, and to correlate NC with future CVD events and relative mortality.

Methods: A prospective cohort study was performed on 12,151 high-risk cardiology outpatients from 2004 until 2014. Anthropometric parameters like body mass index, NC, waist circumference, and hip circumference were measured at baseline and follow-up and compared in different cohorts with high, medium, and low NC. Fatal and non-fatal CVD events were compared in the follow-up study, and survival analysis was conducted. Independent Chi-square tests were performed to compare the incidence of CVD events and mortality among the cohorts and analyze the interactions.

Results: The subjects comprised of 6696 women and 5819 men who completed a mean 8.8-year follow-up. All of the participants had two or more CVD risk factors at baseline. At the end of the study, 4049 CVD events had occurred in 2304 participants. The incidence of non-fatal CVD events was 14.08, 16,65, and 25.21 % in the low-NC, medium-NC, and high-NC cohorts, respectively (p < 0.001). The all-cause mortality was 9.77, 11.93, and 19.31 %, and CVD mortality, 4.00, 6.29, and 8.01 %, respectively (p < 0.001). Compared with baseline, the number of CVD risk factors in participants had increased from 2.6, 3.0, and 3.4 to 3.5, 4.1, and 4.7 in the low-, medium-, and high-NC cohorts (34, 36, and 38 %), respectively. The event-free survival rate was 95.32, 80.15, and 75.47 %, respectively.

Conclusions: A higher NC indicated a higher incidence of future fatal and non-fatal CVD events and all-cause mortality in both male and female high-risk participants. CVD risk factors increased more in the higher NC group. NC as a novel indicator of CVD showed good predictive ability for CVD events and mortality in a high-risk population.
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http://dx.doi.org/10.1186/s12944-016-0218-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4779588PMC
March 2016

Effect of continuous positive airway pressure on blood pressure in hypertensive patients with coronary artery bypass grafting and obstructive sleep apnea.

Int J Clin Exp Med 2014 15;7(11):4308-15. Epub 2014 Nov 15.

Department of Cardiovascular Medicine, The Fourth Affiliated Hospital of Harbin Medical University No. 37 Yiyuan Street, Nangang District, Harbin 150001, China.

Background: Previous studies have documented that obstructive sleep apnea (OSA) increases the incidence of hypertension, respiratory failure and unexpected post-operative deaths during night in coronary artery bypass grafting (CABG) patients. We hypothesized that continuous positive airway pressure (CPAP) reduces blood pressure in these patients.

Methods: We conducted a prospective, controlled study in 51 patients. The subjects received CPAP treatment were defined as CPAP group, whereas those refused to use CPAP were served as controls. Blood pressure was measured by 24 h ambulatory blood pressure at baseline and at six months.

Results: Fifty-one patients completed the study. CPAP group and controls had similar characteristics. Compared with the control group, the 24-h SBP and 24-h DBP in the CPAP group had a tendency towards lower levels, but the differences were not statistically significant. But the change of SBP in CPAP treatment was significantly higher than controls (CPAP: 10.0 ± 13.5 mm Hg vs.

Control: 2.9 ± 10.5 mm Hg, P = 0.040). The rate of hypertension control was improved in the CPAP treatment, but had no statistical difference compared to the controls (CPAP, 76.0% vs. CONTROL, 61.5%; P = 0.260). Compared with controls, the proportion of non-dipping hypertension had a markedly improvement in the CPAP group (CONTROL, 46.2% vs. CPAP, 16.0%; P = 0.034).

Conclusions: CPAP therapy decreased SBP and improved the status of non-dipping hypertension and alleviated daytime somnolence in hypertensive patients with CABG and OSA on standardized antihypertensive treatment. But DBP and hypertension control did not significantly change compared with the control group.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4276204PMC
December 2014

Visualization of network target crosstalk optimizes drug synergism in myocardial ischemia.

PLoS One 2014 5;9(2):e88137. Epub 2014 Feb 5.

Department of Endocrinology, the Fourth Affiliated Hospital of Harbin Medical University, Harbin, China.

Numerous drugs and compounds have been validated as protecting against myocardial ischemia (MI), a leading cause of heart failure; however, synergistic possibilities among them have not been systematically explored. Thus, there appears to be significant room for optimization in the field of drug combination therapy for MI. Here, we propose an easy approach for the identification and optimization of MI-related synergistic drug combinations via visualization of the crosstalk between networks of drug targets corresponding to different drugs (each drug has a unique network of targets). As an example, in the present study, 28 target crosstalk networks (TCNs) of random pairwise combinations of 8 MI-related drugs (curcumin, capsaicin, celecoxib, raloxifene, silibinin, sulforaphane, tacrolimus, and tamoxifen) were established to illustrate the proposed method. The TCNs revealed a high likelihood of synergy between curcumin and the other drugs, which was confirmed by in vitro experiments. Further drug combination optimization showed a synergistic protective effect of curcumin, celecoxib, and sililinin in combination against H₂O₂-induced ischemic injury of cardiomyocytes at a relatively low concentration of 500 nM. This result is in agreement with the earlier finding of a denser and modular functional crosstalk between their networks of targets in the regulation of cell apoptosis. Our study offers a simple approach to rapidly search for and optimize potent synergistic drug combinations, which can be used for identifying better MI therapeutic strategies. Some new light was also shed on the characteristic features of drug synergy, suggesting that it is possible to apply this method to other complex human diseases.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0088137PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3914923PMC
September 2014