Optoelectronic Synapses Based on MXene/Violet Phosphorus van der Waals Heterojunctions for Visual-Olfactory Crossmodal Perception.

The crossmodal interaction of different senses, which is an important basis for learning and memory in the human brain, is highly desired to be mimicked at the device level for developing neuromorphic crossmodal perception, but related researches are scarce. Here, we demonstrate an optoelectronic synapse for vision-olfactory crossmodal perception based on MXene/violet phosphorus (VP) van der Waals heterojunctions. Benefiting from the efficient separation and transport of photogenerated carriers facilitated by conductive MXene, the photoelectric responsivity of VP is dramatically enhanced by 7 orders of magnitude, reaching up to 7.7 A W-1. Excited by ultraviolet light, multiple synaptic functions, including excitatory postsynaptic currents, paired-pulse facilitation, short/long-term plasticity and "learning-experience" behavior, were demonstrated with a low power consumption. Furthermore, the proposed optoelectronic synapse exhibits distinct synaptic behaviors in different gas environments, enabling it to simulate the interaction of visual and olfactory information for crossmodal perception. This work demonstrates the great potential of VP in optoelectronics and provides a promising platform for applications such as virtual reality and neurorobotics.

Prevalence and genetic analysis of triplicated α-globin gene in Ganzhou region using high-throughput sequencing.

α-globin gene triplication carriers were not anemic in general, while some studies found that α-globin gene triplication coinherited with heterozygous ß-thalassemia may cause adverse clinical symptoms, which yet lacks sufficient evidence in large populations. In this study, we investigated the prevalence and distribution of α-globin gene triplication as well as the phenotypic characteristics of α-globin gene triplication coinherited with heterozygous ß-thalassemia in Ganzhou city, southern China. During 2021-2022, a total of 73,967 random individuals who received routine health examinations before marriage were genotyped for globin gene mutations by high-throughput sequencing. Among them, 1,443 were α-globin gene triplication carriers, with a carrier rate of 1.95%. The most prevalent mutation was αααanti3.7/αα (43.10%), followed by αααanti4.2/αα (38.12%). 42 individuals had coinherited α-globin gene triplication and heterozygous ß-thalassemia. However, they did not differ from the individuals with heterozygous ß-thalassemia and normal α-globin (αα/αα) in terms of mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) levels. In addition, heterogenous clinical phenotypes were found in two individuals with the same genotype. Our study established a database of Ganzhou α-globin gene triplication and provided practical advice for the clinical diagnosis of α-globin gene triplication.

A 47,XXY Pregnant Woman without the SRY Gene.

Individuals with a 47,XXY karyotype usually present with a male phenotype due to the additional Y chromosome. In this paper, we describe a 47,XXY female who was pregnant with a fetus of the same karyotype based on chromosome analysis of amniotic fluid cells. Further analysis of her Y chromosome indicated that the additional Y chromosome contains no SRY gene on the short arm but carries the azoospermia factor region on the long arm, including azoospermia factor a, b and c (AZFa, AZFb, AZFc). This region may influence her female phenotype. Fertile females with a 47,XXY karyotype and loss of SRY are extremely rare. This paper is the first report of a 47,XXY pregnant woman with a normal phenotype and may enrich our knowledge on 47,XXY individuals.

Modification with CREKA Improves Cell Retention in a Rat Model of Myocardial Ischemia Reperfusion.

Poor cell homing limits the efficacy of cardiac cellular therapy. The homing peptide, cysteine-arginine-glutamic acid-lysine-alanine (CREKA), targets fibrin effectively which is involved in the repair process of tissue injury. Here, we assessed if CREKA-modified stem cells had enhanced fibrin-mediated homing ability resulting in better functional recovery and structural preservation in a rat myocardial injury model. CREKA-modified mesenchymal stem cells (CREKA-MSCs) were obtained via membrane fusion with CREKA-modified liposomes. The fibrin targeting ability of CREKA-MSCs was examined both in vitro and in vivo. Under both static and flow conditions in vitro, CREKA significantly enhanced MSCs binding ability to fibrin clots (2.6- and 2.3-fold, respectively). CREKA-MSCs showed 6.5-fold higher accumulation than unmodified MSCs in injured rat myocardium one day after administration, resulting in better structural preservation and functional recovery. Fibrin is, therefore, a novel target for enhancing homing of transplanted cells to injured myocardium, and the delivery system of fibrin-targeting is on behalf of a universalizable platform technology for regenerative medicine. Stem Cells 2019;37:663-676.

Mineralocorticoid receptor deficiency improves the therapeutic effects of mesenchymal stem cells for myocardial infarction via enhanced cell survival.

The poor survival of stem cells seriously limits their therapeutic efficacy for myocardial infarction (MI). Mineralocorticoid receptor (MR) activation plays an important role in the pathogenesis of multiple cardiovascular diseases. Here, we examined whether MR silencing in bone marrow derived mesenchymal stem cells (MSCs) could improve MSCs' survival and enhance their cardioprotective effects in MI. MSCs from male Sprague-Dawley rats were transfected with adenoviral small interfering RNA to silence MR (siRNA-MR). MR silencing decreased hypoxia-induced MSCs' apoptosis, as demonstrated by Annexin V/7-AAD staining. The mechanisms contributing to the beneficial effects of MR depletion were associated with inhibiting intracellular reactive oxygen species production and increased Bcl-2/Bax ratio. In vivo study, 1 × 106 of MSCs with or without siRNA-MR were injected into rat hearts immediately after MI. Depletion of MR could improve the MSCs' survival significantly in infarcted myocardium, associated with more cardiac function improvement and smaller infarct size. Capillary density were also significantly higher in siRNA group with increased expression of vascular endothelial growth factor. Our study demonstrated that silencing MR promoted MSCs' survival and repair efficacy in ischaemic hearts. MR might be a potential target for enhancing the efficacy of cell therapy in ischaemic heart disease.

Prophylactic Atrial Fibrillation Ablation in Atrial Flutter Patients without Atrial Fibrillation: A Meta-Analysis with Trial Sequential Analysis.

BACKGROUND New-onset atrial fibrillation (AF) is common after atrial flutter (AFL) ablation, but it was unclear whether AF ablation could reduce the incidence of AF in AFL patients without AF history. The present meta-analysis was conducted to evaluate the benefit of prophylactic AF ablation in reducing the occurrence of AF in typical AFL patients. MATERIAL AND METHODS We systematically searched PubMed, EMBASE, and the Cochrane Library from inception to December 2017 for randomized controlled trials (RCTs) that assessed the efficacy of AF ablation in reducing the occurrence of AF in AFL patients without AF. Trial sequential analysis (TSA) was used to control random errors and calculate the required information size. RESULTS Four trials (n=357 patients) met the inclusion criteria and were included in our meta-analysis. The incidence of AF after AFL ablation was 46.4%. We observed that prophylactic AF ablation reduced the AF incidence compared with simple AFL ablation (26.1% versus 46.4%, RR: 0.57, 95% CIs: 0.42-0.76, P=0.0002) with a prolonged procedure duration (P<0.00001) and fluoroscopy time (P=0.004). Further TSA indicated that more RCTs were needed to reach more conclusive results. There was no significant difference in clinical complications (P=0.33) between the 2 groups. CONCLUSIONS This meta-analysis provides evidence that prophylactic AF ablation may be more effective than simple AFL ablation in reducing AF incidence after AFL ablation. Large prospective RCTs are warranted to confirm the benefit of prophylactic AF ablation in AFL patients without AF history.

Association of pre-ablation level of potential blood markers with atrial fibrillation recurrence after catheter ablation: a meta-analysis.

AIMS: The meta-analysis was aimed to search for candidate blood markers whose pre-ablation level was associated with atrial fibrillation (AF) recurrence after radiofrequency catheter ablation (RFCA). METHODS AND RESULTS: A systematic literature search of PubMed, EMBASE, Springer Link, Web of Science, Wiley-Cochrane library, and supplemented with Google scholar search engine was performed. Thirty-six studies covering 11 blood markers were qualified for this meta-analysis. Compared with the nonrecurrence group, the recurrence group had increased pre-ablation level of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), N-terminal pro-brain natriuretic peptide (NT-pro-BNP), interleukin-6 (IL-6), C-reactive protein, low density lipoprotein (LDL), and tissue inhibitor of metal loproteinase-2 (TIMP-2) [standardized mean difference (95% confidence interval): 0.37 (0.13-0.61), 0.77 (0.40-1.14), 1.25 (0.64-1.87), 0.37 (0.21-0.52), 0.35 (0.10-0.60), 0.24 (0.07-0.42), 0.17 (0.00-0.34), respectively], while no statistical difference of pre-ablation level of white blood cell, total cholesterol, triglyceride, and transforming growth factor-ß1 was found. Subgroup analysis demonstrated that ANP was associated with AF recurrence in participants who had no concomitant structural heart diseases (SHD); however, not in participants who had SHD, C-reactive protein was associated with AF recurrence in Asian studies, whereas not in European studies. CONCLUSION: Increased pre-ablation level of ANP, BNP, NT-pro-BNP, IL-6, C-reactive protein, LDL, and TIMP-2 was associated with greater risk of AF recurrence after RFCA.

Long-Term Effects of Atrial Ganglionated Plexi Ablation on Function and Structure of Sinoatrial and Atrioventricular Node in Canine.

BACKGROUND: Long-term effects of ganglionated plexi (GP) ablation on sinoatrial node (SAN) and atrioventricular node (AVN) remain unclear. This study is to investigate the long-term effects of ablation of cardiac anterior right GP (ARGP) and inferior right GP (IRGP) on function and structure of SAN and AVN in canine. METHODS: Thirty-two dogs were randomly divided into an operated group (n = 24) and sham-operated group (n = 8). ARGP and IRGP were ablated in operated group which was randomly divided into three subgroups according to the period of evaluation after operation (1 month, 6 months, 12 months). The functional and histological characteristics of SAN and AVN, as well as the expression of connexin (Cx) 43 and Cx 45 in SAN and AVN, were evaluated before and after ablation. RESULTS: Resting heart rate was increased and AVN effective refractory period was prolonged and sinus node recovery time (SNRT) and corrected SNRT were shortened immediately after ablation. These changes were reverted to preablation level after 1 month. At 1 month, ventricular rate during atrial fibrillation was slowed, atria-His intervals were prolonged, and Cx43 and Cx45 expression in SAN and AVN were downregulated. At 6 months, all changes were reverted to preablation level. The histological characteristics of SAN and AVN did not change. CONCLUSION: Ablation of ARGP and IRGP has short-term effects on function and structure of SAN and AVN rather than long-term effects, which suggests that ablation of ARGP and IRGP is safe. Atrioventricular conduction dysfunction after ablation may be related to downregulated Cx43 and Cx45 expression in AVN.

Long-Term Effects of Ganglionated Plexi Ablation on Electrophysiological Characteristics and Neuron Remodeling in Target Atrial Tissues in a Canine Model.

BACKGROUND: The long-term effects of ganglionated plexi ablation on electrophysiological characteristics and neuron remodeling in target atrial tissues remain unclear. METHODS AND RESULTS: Dogs in group 1 (control, n=8) were not subjected to ganglionated plexi ablation and observed for 1 month, and dogs in groups 2 to 4 (ablation groups, n=8 each) underwent ablation of the right-sided ganglionated plexi and observed for 1, 6, and 12 months, respectively. Atrial electrophysiological characteristics were examined before ablation, immediately and continuously after ablation. Target atrial tissues were subjected to immunohistochemical staining and Western blot analysis. Atrial effective refractory period was significantly prolonged immediately after ablation (P<0.001), and persisted for 1 month (P<0.05). Nerve densities decreased 1 month after ablation (P<0.001). These parameters reverted to preablation levels after 6 and 12 months. In the ablation groups, atrial fibrillation was induced in 5 of 8 dogs after 1 month and in all animals after 6 and 12 months. Atrial fibrillation was not observed in the control group and in the experimental groups immediately after ablation. Moreover, the expression of the growth-associated protein 43 was upregulated after ablation. CONCLUSIONS: Ganglionated plexi ablation effectively prolonged atrial effective refractory period for a short period, but the long-term effects on atrial effective refractory period and the suppression of atrial fibrillation induction were not persistent. Targeted atrial neuron remodeling may be an important mechanism underlying the observed electrophysiological changes.

MicroRNA profiling of atrial fibrillation in canines: miR-206 modulates intrinsic cardiac autonomic nerve remodeling by regulating SOD1.

BACKGROUND: A critical mechanism in atrial fibrillation (AF) is cardiac autonomic nerve remodeling (ANR). MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at the post-transcriptional level. Numerous miRNAs are involved in diseases of the nervous and cardiovascular systems. OBJECTIVE: We aimed to assess the underlying role of miRNAs in regulating cardiac ANR in AF by right atrial tachypacing (A-TP) in canines. METHODS AND RESULTS: Following 4-week A-TP, the superior left ganglionated plexuses (SLGPs), which are embedded in the fat pads of the left atrium, were subjected to miRNA expression profiling to screen preferentially expressed miRNAs. Sixteen miRNAs showed significantly differential expression between the control and A-TP groups, including miR-206, miR-203, miR-224 and miR-137. In particular, we focused on miR-206, which was elevated ~10-fold in A-TP dogs. Forced expression of miR-206 through lentiviral infection based on A-TP in vivo significantly shortened the atrial effective refractory period (AERP) (81 ± 7 vs. 98 ± 7 ms, P < 0.05). Immunohistochemical analysis showed that the regeneration of nerves increased more than 2-fold by miR-206 overexpression (P < 0.01). The expression of superoxide dismutase 1 (SOD1) was repressed by miR-206 overexpression by Western blot and luciferase assay, indicative of SOD1 as a direct target of miR-206. Overexpression of miR-206 increased reactive oxygen species (ROS) levels in vitro and in vivo, whereas miR-206 silencing attenuated irradiation- or A-TP-induced ROS. Knockdown of SOD1 effectively abolished ROS reduction caused by miR-206 silencing. CONCLUSIONS: Our results found the differential expression of miRNAs in response to ANR in AF and elucidated the important role of miR-206 by targeting SOD1. The study illustrated the novel molecular mechanism of ANR and indicated a potential therapeutic target for AF.

Rosuvastatin attenuates atrial structural remodelling in rats with myocardial infarction through the inhibition of the p38 MAPK signalling pathway.

OBJECTIVE: The purpose of this study was to verify the hypothesis that rosuvastatin attenuates atrial structural remodelling in rats with myocardial infarction (MI) through the regulation of the p38 mitogen-activated protein kinase (MAPK) signalling pathway. METHODS: A total of 66 rats were used in this study to establish a model of MI. The 56 rats that survived the first 24h after surgery were randomly divided into four groups: the control group (C group), the rosuvastatin group (R group), the low-dose torasemide group (T1 group), and the high-dose torasemide group (T2 group). The four groups of rats received daily intragastric administration of normal saline, rosuvastatin, or torasemide (T1: 1mg/kg body weight; T2: 2mg/kg body weight) for a total of four weeks. The rats in the sham-operated group (n=14) also received daily intragastric administration of normal saline for four weeks. After four weeks of intervention, the left ventricular end-diastolic pressure (LVEDP) was measured in all groups of rats by haemodynamic methods. The rats were then sacrificed, and the left atrial tissues were collected. The collagen volume fractions (CVFs) in the left atrial tissues were determined using Masson's trichrome staining. The expression of phosphorylated p38 (P-p38) MAPK in the left atrial tissues was examined by immunohistochemistry and western blot analysis. RESULTS: The results showed that LVEDP, CVF, and P-p38 MAPK expression were drastically elevated in the four MI groups in comparison to the sham-operated group (p<0.001). Rosuvastatin elevated the left ventricular fractional shortening (LVFS) and left ventricular ejection fraction (LVEF). Both rosuvastatin and torasemide improved the haemodynamic parameters. No significant difference was detected in LVEDP between the R group and the T1 group (p=0.37). In contrast, LVEDP was significantly higher in the R group than in the T2 group (p <0.05). CVF (%) was markedly decreased in the R group compared to the C, T1, and T2 groups (decreased by 47.4%, 28%, and 20.1%, respectively). Immunohistochemical analysis showed that the indices of P-p38 MAPK positive cells were significantly decreased in the R group in comparison with the C, T1, and T2 groups (decreased by 44.6%, 36.6%, and 21.4%, respectively). Western blot analysis demonstrated that P-p38 MAPK expression was markedly reduced in the R group compared with the C and T1 groups (reduced by 67% and 40.5%, respectively). The level of P-p38 MAPK in the R group was slightly higher than in the T2 group. However, the difference was not statistically significant (p>0.05). CONCLUSION: Rosuvastatin attenuates atrial structural remodelling in rats with MI. The mechanism underlying this phenomenon may be associated with the downregulation of P-p38 MAPK by rosuvastatin.

Transcriptome analysis of canine cardiac fat pads: involvement of two novel long non-coding RNAs in atrial fibrillation neural remodeling.

Intrinsic cardiac autonomic neural remodeling (ANR) has been reported to be involved in the initiation and maintenance of atrial fibrillation (AF). Long non-coding RNAs (lncRNAs) are important orchestrators of gene regulatory networks. However, little is known about the relationships between lncRNAs and cardiac ANR in AF. In this study, second-generation RNA sequencing was performed to examine the transcriptomes of lncRNAs in AF and non-AF canine cardiac fat pads. A total of 61,616 putative lncRNAs were yielded, in which 166 were downregulated and 410 were upregulated with more than twofold change. Bioinformatics analysis showed that the aberrantly expressed genes were associated with neural development, migration and neurodegenerative disorders. On the basis of a series of filtering pipelines, two new lncRNAs, namely, TCONS_00032546 and TCONS_00026102, were selected. Silencing of TCONS_00032546 or TCONS_00026102 with lentiviruses in vivo could significantly shorten or prolong the atrial effective refractory period thereby increasing or preventing AF inducibility by promoting or inhibiting the neurogenesis. Besides, the expression of CCND1-FGF19-FGF4-FGF3 gene cluster and SLC25A4, the nearby genes of TCONS_00032546 and TCONS_00026102, were negatively correlated with that of lncRNAs. Furthermore, combining bioinformatics analysis with literature review, TCONS_00032546 and TCONS_00026102 may induce effects by increasing the CCND1-FGF19-FGF3-FGF4 gene cluster and SLC25A4 via complex mechanisms during neural remodeling. Taken together, dysregulated lncRNAs may play regulatory roles in AF neural remodeling, which may further provide potential therapeutic targets for prophylaxis and treatment of AF.

Activation of PPAR-γ ameliorates pulmonary arterial hypertension via inducing heme oxygenase-1 and p21(WAF1): an in vivo study in rats.

AIMS: Our previous study has indicated that activation of PPAR-γ inhibits the proliferation of rat pulmonary artery smooth muscle cells (PASMCs) in vitro through inducing the expression of heme oxygenase-1 (HO-1), which in turn up-regulates the p21(WAF1) expression. In the present study, we intended to determine whether similar mechanisms have been involved in activation of PPAR-γ inhibition of development of rat PAH model. MATERIAL AND METHODS: Rat pulmonary arterial hypertension (PAH) model was established by subcutaneous injection of monocrotaline (MCT). Rosiglitazone was administered to activate PPAR-γ. Zinc protoporphyria IX (ZnPP-IX), was used to confirm the role of HO-1 in mediating PPAR-γ function. Parameters including the right ventricle systolic pressure (RVSP), the right ventricular hypertrophy (RVH) and the percentage of medial wall thickness were used to evaluate the development of PAH. Immunoblotting was used to determine the expression of HO-1 and p21(WAF1). KEY FINDINGS: Rosiglitazone significantly decreased the RVSP and inhibited the RVH in MCT-induced rat PAH model, and partially inhibited the pulmonary vascular remodeling. These effects were coupled with the sequential increase of HO-1 and p21(WAF1) expressions by rosiglitazone. SIGNIFICANCE: Activation of PPAR-γ benefits PAH by inhibiting proliferation of PASMCs and reducing pulmonary vascular remodeling. The present study suggests that enhancing PPAR-γ activity might have potential value in clinical treatment of PAH.

Renin-angiotensin system inhibitors prevent the recurrence of atrial fibrillation: a meta-analysis of randomized controlled trials.

OBJECTIVE: This study was designed to assess whether angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) could prevent the recurrence of atrial fibrillation (AF). METHODS: A systemic literature search of PubMed, EMBASE, and Cochrane Controlled Trials Register till 2012 was performed to identify randomized controlled trials involving the prevention of recurrence of AF with renin-angiotensin system blockade therapy. Subgroup analysis and meta-regression were performed. Publication bias was checked through funnel plot and Egger's test. RESULTS: Twenty-one randomized controlled trials including 13,184 patients with AF were identified. Overall, the recurrence of AF was significantly reduced in patients using ACEI/ARBs [odds ratio (OR), 0.43; 95% confidence interval (CI), 0.32-0.56; P < 0.00001], especially both in irbesartan subgroup (OR, 0.38; 95% CI, 0.21-0.68; P = 0.001) and in patients receiving antiarrhythmic drug (AAD) (OR, 0.37; 95% CI, 0.29-0.48; P < 0.00001), and there was no significant difference between ACEIs and ARBs (ACEIs: OR, 0.42; 95% CI, 0.31-0.57 and ARBs: OR, 0.42; 95% CI, 0.31-0.57). Moreover, it was found that the benefits of ACEI/ARBs revealed positive correlation to systolic blood pressure (regression coefficient: -0.0700257, P = 0.000) in no-AAD users. CONCLUSIONS: ACEI/ARBs are effective on the secondary prevention of AF, especially in patients receiving AAD and suffering from hypertension.

An altered expression of genes involved in the regulation of ion channels in atrial myocytes is correlated with the risk of atrial fibrillation in patients with heart failure.

The aim of this study was to investigate the correlation between the altered expression of genes involved in the regulation of ion channels in atrial myocytes and the risk of atrial fibrillation (AF) in patients with heart failure (HF). Right atrial appendages were obtained from 18 HF patients and 18 patients with normal cardiac functions who had undergone surgery. The mRNA expression levels of Kv4.3α, KvLQT1, Kv1.5, L-Caα1c and NCX were measured by reverse transcription-PCR (RT-PCR). Protein expression levels were also detected by western blotting. In comparison with the control group exhibiting normal cardiac functions, the mRNA and protein expression levels of Kv4.3α, KvLQT1 and L-Caα1c were significantly reduced in HF patients. By contrast, the mRNA and protein expression levels of NCX were significantly increased in HF patients compared with the control group (P<0.01). The mRNA expression levels of Kv1.5 were not evidently altered. We demonstrated that increased levels of Kv4.3α, KvLQT1 and L-Caα1c and decreased levels of NCX are correlated with the risk of AF in HF patients. Changes in the gene expression of ion channel-related proteins may therefore be used as biological markers of AF occurring in HF patients in future studies.

MicroRNA-1 accelerates the shortening of atrial effective refractory period by regulating KCNE1 and KCNB2 expression: an atrial tachypacing rabbit model.

BACKGROUND: The potential mechanisms of microRNA-1 (miR-1) in the electrical remodeling of atrial fibrillation remain unclear. The purpose of this study was to evaluate the effects of miR-1 on the atrial effective refractory period (AERP) in a right atrial tachypacing model and to elucidate the potential mechanisms. METHODS AND RESULTS: QRT-PCR and western blot were used to detect the expression of the miR-1, KCNE1, and KCNB2 genes after 1-week of right atrial tachypacing in New Zealand white rabbits. The AERP was measured using a programmable multichannel stimulator, and atrial fibrillation was induced by burst stimulation in vivo. The slowly activating delayed rectifier potassium current (IKs) and AERP in atrial cells were measured by whole cell patch clamp in vitro. Right atrial tachypacing upregulated miR-1 expression and downregulated KCNE1 and KCNB2 in this study, while the AERP was decreased and the atrial IKs increased. The downregulation of KCNE1 and KCNB2 levels was greater when miR-1 was further upregulated through in vivo lentiviral infection. Electrophysiological tests indicated a shorter AERP, a great increase in the IKs and a higher atrial fibrillation inducibility. In addition, similar results were found when the levels of KCNE1 and KCNB2 were downregulated by small interfering RNA while keeping miR-1 level unaltered. Conversely, knockdown of miR-1 by anti-miR-1 inhibitor oligonucleotides alleviated the downregulation of KCNE1 and KCNB2, the shortening of AERP, and the increase in the IKs. KCNE1 and KCNB2 as the target genes for miR-1 were confirmed by luciferase activity assay. CONCLUSIONS: These results indicate that miR-1 accelerates right atrial tachypacing-induced AERP shortening by targeting potassium channel genes, which further suggests that miR-1 plays an important role in the electrical remodeling of atrial fibrillation and exhibits significant clinical relevance as a potential therapeutic target for atrial fibrillation.

Rosuvastatin changes cytokine expressions in ischemic territory and preserves heart function after acute myocardial infarction in rats.

AIM: To investigate the mechanism of rosuvastatin in preserving cardiac function after acute myocardial infarction (AMI) in a rat model. METHODS: Sprague-Dawley rats were randomized to receive either rosuvastatin (5 mg/kg every day) or placebo (0.5% CMC-Na), respectively, by daily gavage from 7 days before AMI. Acute myocardial infarction (AMI) model was induced by left anterior descending coronary artery ligation through a lateral thoracotomy in rats. The expressions of stromal-cell-derived factor 1 (SDF-1), chemokine motif CXC receptor 4 (CXCR-4), vascular endothelial growth factor (VEGF), and intercellular adhesion molecule 1 (ICAM-1) in peri-infarction region and nonischemic region at different time points were determined by the Western blot analysis. Immunohistochemistry analysis was performed on the 28th day after AMI to investigate the accumulation of CD90+, CD133+, and c-kit+ progenitor cells in the peri-infarction region. Masson staining and echocardiograph were performed to evaluate the left ventricular remodeling and postinfarction cardiac function 4 weeks after AMI. RESULTS: Western blot analysis showed that rosuvastatin could change the cytokine expressions in the peri-infarction region by upregulating the SDF-1 expression and downregulating the expressions of CXCR-4, ICAM-1, and VEGF in 4 to 14 days after AMI. Immunohistochemistry analysis showed that rosuvastatin treatment was associated with increased accumulation of CD90+, CD133+, and c-kit+ progenitor cells in the peri-infarction region. Masson staining and echocardiograph confirmed that rosuvastatin could attenuate left ventricular remodeling and improve postinfarction systolic function. CONCLUSION: The data suggest that rosuvastatin can protect the heart from ischemic injury and preserve the cardiac function in rats in vivo. The changing expressions of SDF-1, CXCR-4, ICAM-1, and VEGF, and the accumulation of progenitor cells were involved in this process.

High density lipoprotein cholesterol promotes the proliferation of bone-derived mesenchymal stem cells via binding scavenger receptor-B type I and activation of PI3K/Akt, MAPK/ERK1/2 pathways.

High-density lipoprotein (HDL) possesses protective properties in cardiovascular diseases. However, the effect of HDL on the mesenchymal stem cells (MSCs), which could be mobilized to the damaged myocardial tissue, has not been well elucidated yet. In the current study, we investigated the effect of HDL on the proliferation of MSCs so as to reveal its molecular mechanisms. MSCs derived from rats were treated with HDL in different concentrations and for different periods. The proliferation of MSCs was measured with MTT and BrdU cell proliferation assay. The phosphorylation of Akt, ERK1/2 and the expression of p21 were evaluated by Western blotting. After the activity of respective pathways was down-regulated by the specific inhibitor and the gene of scavenger receptor-B type I (SR-BI) was knocked down by RNA interference, BrdU assay was performed to examine this effect of HDL on MSCs. We found that the proliferation of MSCs induced by HDL, in a time- and concentration-dependent manner, was the phosphorylation of Akt- and ERK1/2-dependent, which was significantly attenuated by the specific inhibitor to respective pathways. Moreover, MAPK/ERK1/2 pathway exerted a more dominating effect on this process. SR-BI contributed to HDL-induced proliferation of MSCs, which was effectively abolished by the silencing of SR-BI. The results suggested that HDL was capable of improving MSCs proliferation, in which MAPK/ERK1/2 and PI3K/Akt pathways involved and SR-BI played a critical role as well.