Screening lncRNAs essential for cardiomyocyte proliferation by integrative profiling of lncRNAs and mRNAs associated with heart development.

BACKGROUND: The proliferation potential of mammalian cardiomyocytes declines markedly shortly after birth. Both long non-coding RNAs (lncRNAs) and mRNAs demonstrate altered expression patterns during cardiac development. However, the role of lncRNAs in the cell cycle arrest of cardiomyocytes remains inadequately understood. METHOD: The expression pattern of lncRNAs and mRNAs was analyzed in mouse hearts exhibiting varying regenerative potentials on postnatal days (P) 1, 7, and 28. Weighted correlation network analysis (WGCNA) was employed to elucidate the co-expression relationship between lncRNAs and mRNAs. Protein-protein interaction (PPI) network was built using the STRING database, and hub lncRNAs were identified by CytoHubba. Molecular Complex Detection (MCODE) was used to screen core modules of the PPI network in Cytoscape. Upstream lncRNAs and miRNAs which may regulate mRNAs were predicted using miRTarBase and AnnoLnc2, respectively. Myocardial infarction (MI) was induced by ligation of the left anterior descending coronary artery. RESULTS: Compared with the P1 heart, 618 mRNAs and 414 lncRNAs displayed. transcriptional changes in the P7 heart, while 2358 mRNAs and 1290 lncRNAs showed from P7 to P28. Gene Ontology (GO) analysis revealed that module 1 in the both comparisons was enriched in the mitotic cell cycle process. 2810408I11Rik and 2010110K18Rik were identified as hub lncRNAs and their effects on the proliferation of cardiomyocytes were verified in vitro. Additionally, four lncRNA-miRNA-mRNA regulatory axes were predicted to explain the mechanism by which 2810408I11Rik and 2010110K18Rik regulate cardiomyocyte proliferation. Notably, the overexpression of 2810408I11Rik enhances cardiomyocyte proliferation and heart regeneration in the adult heart following MI. CONCLUSION: This study systematically analyzed the landscape of lncRNAs and mRNAs at P1, P7, and P28. These findings may enhance our understanding of the framework for heart development and could have significant implications for heart regeneration.

Smooth Muscle Overexpression of PGC1α Attenuates Atherosclerosis in Rabbits.

[Figure: see text].

A simplified repair method for adult Ebstein's anomaly.

Ebstein's anomaly (EA) is a rare but difficult to manage congenital heart disease with a wide spectrum of clinical manifestations. We present a simplified repair method which combines the plication of the atrialized right ventricle, tricuspid leaflet repair and ring annuloplasty. This method is suitable for older adult EA patients with progressive right heart dysfunction symptoms. Compared with complex repair methods (such as Cone reconstruction) this simplified repair method can reduce surgical risk, and achieve mild or less tricuspid regurgitation with acceptable long-term effects compared with prosthetic valve replacement.

Surgical Repair for Acute Myocardial Infarction Induced Ventricular Septal Defect: Does Time Matter?

OBJECTIVE: Ventricular septal defect (VSD) induced by acute myocardial infarction (AMI) is rare but lethal, with high mortality even after surgical repair. Our aim was to assess the association between the time interval and surgical repair effects in patients with VSD following AMI. METHODS: From January 2003 to December 2017, 14 patients with VSD induced by AMI received surgical therapy in our department. We retrospectively reviewed the patients' clinical manifestations, surgical methods, and outcomes. According to the time interval from AMI onset and surgery, we divided the patients into two groups: Group 1 (N = 9), more than one week, and Group 2 (N = 5), less than one week. A comparison study was performed, and differences were analyzed. RESULTS: The mean age of the entire group was 65.5±3.3 years, with 78.6% males (11/14). VSDs were anterior apical in 10 (71.4%) and posterior inferior in 4 (28.6%) patients. The average size of the VSD was 15.8±5.8 mm. Compared with Group 1, Group 2 had poorer left ventricular function (LVEF 40.8±10.3% vs. 30.4±2.3%, P = 0.035) and a higher rate of urgent procedures (11.1% vs. 100.0%, P = 0.003). The mortality rate was 14.3% (2/14). Mechanical support was more common in Group 2 than Group 1. No resistant shunt or death was found during follow up. CONCLUSIONS: VSD following AMI is safer for more than one week, but surgical treatment is also acceptable for patients requiring urgent surgery due to hemodynamic instability. Mechanical assistive devices can improve the perioperative success rate.

Left Atrial Appendage Circular RNAs Are New Predictors of Atrial Fibrillation Recurrence After Surgical Ablation in Valvular Atrial Fibrillation Patients.

BACKGROUND: Atrial fibrillation (AF) recurrence after ablation will increase mortality and morbidity during follow up. We attempted to evaluate the relationship between circular RNAs (circRNA) and AF recurrence to establish a predictive model for early intervention. METHODS: Patients who received surgical ablation retrospectively were analyzed. The expression of circRNAs were detected in the left atrial appendage. The independent risk factors of late recurrence were analyzed by multivariate analysis. The predictive model was visualized by Nomogram and tested by receiver operating characteristic curve and calibration plot. Kaplan-Meier plot was used to compare the rate of freedom from AF recurrence after surgery. The relationships between circRNAs and clinical characteristics were detected by Spearman's correlation analysis. RESULTS: A total of 136 patients were enrolled from September 2018 to June 2019, 55 patients experienced late recurrence during one-year follow up. Increased age, longer AF duration and increased circ 81906-RYR2, circ 44782-LAMA2, circ 418-KCNN2 and circ 35880-ANO5 were detected in recurrent patients. Multivariate analysis revealed that increased age (odds ratio (OR)=1.072, P = 0.006), longer AF duration (OR=1.007, P = 0.036) and increased circ 81906-RYR2 (OR=2.210, P < 0.001) were independent risk factors for late recurrence. Area under the curve was 0.77, and the cut-off value was 70 points of the predictive model. Kaplan-Meier plots showed that patients over 70 points tended to experience AF recurrence. CONCLUSION: Circ 81906-RYR2 could be a new predictor of late recurrence after surgical ablation. A predictive model consists of age, atrial fibrillation duration, and circ 81906-RYR2 was alternative for early intervention of AF recurrence.

Safety of open limited surgery for septuagenarian and octogenarian acute type A aortic dissection patients: a retrospective cohort study.

Background: Surgical strategies in older adult patients with acute type A aortic dissection (aTAAD) are crucial. We investigated the safety and efficiency of open limited surgery for septuagenarian and octogenarian patients with aTAAD. Methods: Between 2011 and 2019, 1,092 patients diagnosed with aTAAD underwent open surgery in Nanjing Drum Tower Hospital. Patients were divided into two groups based on age: <70 years (n=956) and ≥70 years (n=136). Preoperative baseline characteristics, operative data, and postoperative outcomes were compared between the two groups. To investigate the safety and efficiency of the surgical approach for those aged ≥70 years, we separated these patients into two groups: (I) those who underwent root-sparing surgery and less-invasive arch surgery (Limited group; n=86); and (II) all others (Extensive group; n=50). Results: Mortality was significantly higher in those aged ≥70 years than in those <70 years (20.6% vs. 13.2%; P=0.000), with age being a strong risk factor for postoperative mortality [odds ratio (OR) 1.619; 95% confidence interval (CI): 1.015-2.582; P=0.043]. Patients aged ≥70 years tended to receive less invasive surgery, and the rates of root replacement and arch replacement were lower. Patients in the limited surgery group had a higher rate of pericardial tamponade, and the durations of surgery, hypothermic circulation arrest, cardiopulmonary bypass, and aortic clamp were all significantly shorter than in the extensive group. Mortality and postoperative complications were also lower in the limited surgery group. Conclusions: Although older age was a risk factor for open surgery for aTAAD, limited surgical techniques could lower the mortality and morbidity regardless of the need for extensive surgery.

Short and mid-term effects of modified release technique in rheumatic mitral valve repair.

OBJECTIVE: Repair or replacement remains debatable in rheumatic heart disease. To regain optimal mean transvalvular pressure gradients and end-diastolic peak flow velocity, the modified release technique combined peeling in the anterior leaflet and separated the shortened chordal. In the end, the short and mid-term outcomes of the modified release technique were evaluated. METHODS: We retrospectively analyzed a series of 128 patients with rheumatic mitral stenosis, from January 2018 to July 2021 in our center. All patients undergoing mitral valve repair were using the modified release technique. The effect of mitral valve repair was evaluated by intraoperative transesophageal echocardiography and postoperative transthoracic echocardiography. RESULTS: All the 128 patients successfully repaired the mitral valve. The intraoperative transesophageal echocardiography showed trivial or mild regurgitation. The aortic valve was repaired without obvious regurgitation in 12 cases, 5 cases received an aortic valve replacement, 89 cases underwent tricuspid annuloplasty. There were no blood transfusions in most patients, no deaths nor complications during peri-operation, also, no deaths and adverse events were observed during the follow-up period from 3 to 42 months. During the follow-up, 122 cases had no mitral valve regurgitation and 2 cases of moderate regurgitation, 4 cases of mild to moderate regurgitation. The mean peak flow velocity was 1.2 ± 0.3 m / s, no new-onset stenosis occurred. CONCLUSION: Modified release technique is safe and feasible. Its durability is acceptable in the short and mid-term, with no new-onset stenosis during the follow-up.

Analysis of risk factors for postoperative mortality in acute type A aortic dissection patients under different critical levels.

We built up a risk stratification model to divide acute type A aortic dissection (aTAAD) patients into low- and high-risk groups, further, to evaluate the risk factors for postoperative mortality. A total of 1364 patients from 2010 to 2020 in our center were retrospectively analyzed. More than twenty clinical variables were related with postoperative mortality. The postoperative mortality of the high-risk patients was doubled than the low-risk ones (21.8% vs 10.1%). The increased operation time, combined coronary artery bypass graft, cerebral complications, re-intubation, continuous renal replacement therapy and surgical infection were risk factors of postoperative mortality in low-risk patients. In addition, postoperative lower limbs or visceral malperfusion were risk factors, axillary artery cannulation and moderate hypothermia were protective factors in high-risk patients. A scoring system for quick decision-making is needed to select appropriate surgical strategy in aTAAD patients. For low-risk patients, different surgical treatments can be performed with similar clinical prognosis. Limited arch treatment and appropriate cannulation approach are crucial in high-risk aTAAD patients.

"Collar-like" neocommissure in mitral valve repair for extensive commissural prolapse.

Objectives: Mitral valve repair for extensive commissural prolapse is complex; several methods have been reported with variable results. To restore the leaflet area, we introduced an innovative and effective method rather than a simple folding technique through reconstructing a neocommissure with a "collar-like" plasty technique. Methods: From 2016 to 2021, 62 patients with mitral valve extensive commissural prolapse that received the "collar-like" plasty technique were included. Results: The mean age was 51.7 ± 13.8 years, and 38 (61%) were female. Postplasty transesophageal echocardiography showed the mean transvalvular pressure gradients were 3.8 ± 1.2 mm Hg, end diastolic peak flow velocity was 1.1 ± 0.3 m/s, and coaptation height was 7.9 ± 1.1 mm. During the follow-up period of 3 to 6 months, no deaths or cardiovascular-/valvular plasty-related adverse events occurred. All patients regained their heart function and returned to normal physical activities. Conclusions: The "collar-like" plasty technique can be safely performed for patients with extensive commissural prolapse. Echocardiography revealed that the technique can restore the leaflet area of low transvalvular pressure and flow velocity.

Triglyceride-glucose index in the prediction of major adverse cardiovascular events in patients with type 2 diabetes mellitus after coronary artery bypass surgery: A retrospective cohort study.

Background: Insulin resistance (IR) is a significant risk factor for cardiometabolic diseases and a defining feature of type 2 diabetes mellitus (T2DM). This study aimed to examine the potential value of triglyceride-glucose (TyG) index as a predictor of prognosis in coronary heart disease (CHD) patients with T2DM after coronary artery bypass grafting (CABG) surgery and to facilitate the identification of those at high risk of major adverse cardiovascular events (MACEs) for closer monitoring or possible early intervention. Methods: This study enrolled 386 T2DM patients who underwent CABG surgery at Nanjing Drum Tower Hospital. Patients were separated into two groups according to the median preoperative TyG Index. The Kaplan-Meier plot was used to compare the rate of MACEs-free survival in T2DM patients after CABG. The independent risk factors for the occurrence of MACEs were investigated using multivariate analysis. Nomogram was used to depict the predictive model. Results: Significantly more MACEs occurred in individuals with higher medians of the TyG index (65 (33.7%) vs. 39 (20.2%), p=0.003). TyG index [hazard ratio (HR) 12.926], LVEF [hazard ratio (HR) 0.916], and NYHA functional class III/IV [hazard ratio (HR) 4.331] were identified as independent predictors of MACEs incidence in post-CABG T2DM patients by multivariate analysis. The area under the curve (AUC) for predicting MACEs using the TyG index was 0.89 at five years. Combining the TyG index, LVEF, and NYHA functional class III/IV to build a novel risk assessment model for postoperative MACEs, the AUC climbed to 0.93 at five years. With AUCs, the nomogram comprised of the TyG index, LVEF, and NYHA functional class III/IV demonstrated strong specificity in the training and test sets. Conclusions: The incidence of MACEs is high among post-CABG T2DM patients with a high TyG index. TyG index improves the diagnostic accuracy of MACEs, especially at long-term follow-up. A high TyG index may serve as an early warning signal for individuals to undertake lifestyle adjustments that can reduce the progression or incidence of MACEs.

The impact of age in acute type A aortic dissection: a retrospective study.

BACKGROUND: Acute type A aortic dissection (aTAAD) is a lethal disease and age is an important risk factor for outcomes. This retrospective study was to analyze the impact of age stratification in aTAAD, and to provide clues for surgeons when they make choices of therapy strategies. METHODS: From January 2011 to December 2019, 1092 aTAAD patients from Nanjing Drum Tower Hospital received surgical therapy. Patients were divided into 7 groups according to every ten-year interval (20-80 s). The differences between the groups were analyzed in terms of the baseline preoperative conditions, surgical methods and postoperative outcomes of patients of different age groups. During a median follow-up term of 17 months, the survival rates were compared among 7 groups through Kaplan-Meier analysis. RESULTS: The median age was 52.0 years old in whole cohort. The multiple comorbidities were more common in old age groups (60 s, 70 s, 80 s), while the 20 s group patients had the highest proportion of Marfan syndrome (28.1%). Preoperative hypotension was highest in 80 s (16.7%, P = 0.038). Young age groups (20-60 s) had a higher rate of root replacement and total arch replacement, which led to a longer duration of operation and hypothermic circulation arrest. The overall mortality was 14.1%, the tendency of mortality was increased with age except 20 s group (33.3% in 80 s, P = 0.016). The postoperative morbidity of gastrointestinal bleeding and bowel ischemia were 16.7% and 11.1% in 80 s group. CONCLUSIONS: Age is a major impact factor for aTAAD surgery. Old patients presented more comorbidities before surgery, the mortality and complications rate were significantly higher even with less invasive and conservative surgical therapy. But the favorable long-term survival indicated that the simple or less extensive arch repair is the preferred surgery for patients over 70 years old.

Epicardial injection of allogeneic human-induced-pluripotent stem cell-derived cardiomyocytes in patients with advanced heart failure: protocol for a phase I/IIa dose-escalation clinical trial.

INTRODUCTION: Heart failure (HF) is a growing global public health burden. However, due to the very limited regenerative capacity of mature cardiomyocytes in the adult mammalian heart, conventional treatments can only improve the symptoms of HF but fail to restore cardiac function. Heart transplantation is limited by a severe shortage of donors. Cell-based transplantation for the treatment of HF has become a promising strategy. Human-induced-pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have been tested in animal models to assess safety and efficacy. This study aims at evaluating the safety and efficacy of epicardial injection of hiPSC-CMs in patients with advanced HF during coronary artery bypass grafting (CABG) surgery. METHODS: This study is a dose-escalation, placebo-controlled, single-centre phase I/IIa clinical trial. Dose escalation will be guided by a modified 3+3 design for three doses (1×108, 2×108 and 4×108 cells, sequentially). Patients with advanced heart failure will be enrolled and randomly allocated to receive epicardial injection of hiPSC-CMs during CABG surgery or CABG surgery alone, followed by a 12-month follow-up investigation. The primary endpoint is to assess the safety of hiPSC-CMs transplantation, including haemodynamic compromised sustained ventricular arrhythmias and newly formed tumours during 6 months postoperatively. The secondary endpoint is to evaluate the efficacy of epicardial injection of hiPSC-CMs and CABG surgery combination by comparison with CABG surgery alone. ETHICS AND DISSEMINATION: The study protocol has been approved by the Institutional Ethical Committee of Nanjing Drum Tower Hospital (No. SC202000102) and approved by National Health Commission of the PRC (MR-32-21-014649). Findings will be disseminated to the academic community through peer-reviewed publications and presentation at national and international meetings. TRIAL REGISTRATION NUMBER: NCT03763136.

Generation of induced pluripotent stem cells (NJDTHi001-A) from a Danon disease child with mutation of c.467 T > G in LAMP2 gene.

The induced pluripotent stem cells (iPSCs) were generated from peripheral blood mononuclear cells (PBMCs) isolated from a male child with Danon disease. Next-generation sequencing (NGS) revealed a stop gained mutation c.467 T > G in LAMP2 gene. PBMCs were reprogrammed by using non-integrating Sendai reprogramming kits. It is a possible cell model to screen alternative medicine treatment of the Danon disease.

Expression Profiles of Circular RNA in Human Atrial Fibrillation With Valvular Heart Diseases.

Circular RNAs (circRNA) are involved in a variety of human heart diseases, however, circRNA expression profiles and circRNA-miRNA-mRNA regulatory network in human atrial fibrillation (AF) especially with valvular heart diseases (VHD) remain poorly understood. A high-throughput RNA sequencing was used to investigate the differentially expressed circRNAs in left atrial appendage from VHD patients with or without persistent AF. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to predict the potential functions of the host genes of differentially expressed circRNA and their downstream targets. CircRNA-miRNA-mRNA regulatory network was constructed to identify mechanisms underlying circRNAs. qRT-PCR and sanger sequencing were further performed to validate the results. Compared with sinus rhythm (SR) patients, there were 3094 upregulated and 4472 downregulated circRNAs in AF patients respectively. The expression of 10 most differentially expressed circRNAs (circ 255-ITGA7, circ 418-KCNN2, circ 13913-MIB1, circ 44670-BARD1, circ 44782-LAMA2, circ 81906-RYR2, circ 35880-ANO5, circ 22249-TNNI3K, circ 3136-TNNI3K, circ 56186-TNNI3K) between SR and persistent AF patients were verified by qRT-PCR. In addition, specific back-splicing sites of these circRNAs was confirmed by sanger sequencing. GO and KEGG pathway analysis indicated that cAMP signal pathway and Wnt signal pathway might play important role in the development of AF in VHD patients, which might be affected by circRNAs. This study provided a preliminary landscape of circRNAs expression profiles which are involved in persistent AF due to VHD, and established the possibility for future related researches in this field.

The PGC-1α/NRF1/miR-378a axis protects vascular smooth muscle cells from FFA-induced proliferation, migration and inflammation in atherosclerosis.

BACKGROUND AND AIMS: Atherosclerosis (AS) is the leading cause of cardiovascular diseases. PGC-1α is a key regulator of cellular energy homeostasis, but its role in AS remains debatable. METHODS AND RESULTS: In our study, PGC-1α was shown to be significantly decreased in the media of human atherosclerotic vessels. To explore whether miRNAs might be regulated by PGC-1α in vascular smooth muscle cells (VSMCs), microarray analysis was performed. Microarray and Pearson's correlation analysis showed that PGC-1α and miR-378a were positively correlated in vivo and in vitro. As an upstream co-activator, PGC-1α was found to regulate miR-378a through binding to the transcriptional factor NRF1 in VSMCs. Therefore, the decreased expression of PGC-1α might account for suppression of miR-378a in VSMCs in AS. Furthermore, IGF1 and TLR8, two genes known to be aberrantly up-regulated in atherogenic vessels, were identified as direct targets of miR-378a. In vitro up-regulation of miR-378a markedly inhibited free fatty acid (FFA)-induced VSMC proliferation, migration and inflammation through targeting IGF1 and TLR8. CONCLUSIONS: These findings highlight the protective role of the PGC-1α/NRF1/miR-378a regulatory axis in AS progression and suggest miR-378a as potential therapeutic target for AS treatment.

Aortic dissection patients mimic acute coronary syndrome with preoperative antiplatelet therapy.

BACKGROUND: Acute Stanford type A aortic dissection (ATAAD) is often misdiagnosed as an acute coronary syndrome (ACS), and antiplatelet therapy (APT) for ACS will influence the timing and outcome of ATAAD. We reviewed the surgical outcome of these misdiagnosed ATAAD patients. METHODS: From January 2011 to December 2015, 309 ATAAD patients received surgical therapy in our department, among whom 15 patients were misdiagnosed as ACS and took oral APT. We retrospectively reviewed the data of the perioperative and follow-up period. RESULTS: The average age of these 15 patients was 60.6±8.7 years old (9 males, 6 females). Five patients took aspirin orally, and 10 took aspirin and clopidogrel. Operations were performed 7, 3, and 1 day after stopping the agents in 2, 3, and 1 patient, respectively; the other 5 patients received emergency operation without stopping the agents. The cardiopulmonary bypass (CPB) time was 259.7±64.8 minutes, aortic cross-clamp time was 181.0±51.7 minutes, and selective cerebral perfusion and lower body arrest time were 34.9±8.1 minutes. There were two in-hospital deaths due to circulation failure (mortality 13.3%). The average drainage volume in the first 24 h after operation was 800.7±598.8 mL. During a mean follow-up period of 20.6±17.4 months, one patient had a sudden death. CONCLUSIONS: ATAAD misdiagnosed as ACS is not rare, and APT will increase the risk of bleeding in ATAAD patients. The decision of operation time relies on considering the balance between the rupture risk of aortic dissection and the hemorrhage risk of APT. The emergency operation for these patients will increase bleeding and transfusion.

Root reconstruction for proximal repair in acute type A aortic dissection.

BACKGROUND: Retrospective compared the results of root reconstruction and root replacement for acute type A aortic dissection (ATAAD) patients and observed the rate of aortic insufficiency (AI) and aortic root dilation in the midterm follow-up period. METHODS: From 2008-2016, 427 ATAAD patients received surgical therapy in our center. There were 328 male and 99 female patients, aging from 22 to 83 years with a mean age of (51.1±12.5) years. These patients were divided into two major groups: 298 cases with root reinforcement reconstruction (Root Reconstruction), 129 cases with Bentall procedure (Root Replacement). RESULTS: The 30-day mortality was 7.7% (33/427), while no difference between the 2 procedures (8.1% and 7.0%, P=0.844). Cross-clamp, cardiopulmonary bypass, and circulatory arrest times of all the patients were 252.5±78.1, 173.6±68.9, 30.7±9.5 minutes, respectively. In the average follow-up time of (34.5±26.1) months, midterm survival rates were similar between the 2 procedures (86.2% and 86.0%, P=0.957). Only one patient received redo Bentall procedure because of severe aortic regurgitation and dilated aortic root (50 mm) in the Root Reconstruction Group. CONCLUSIONS: The indication of root management of ATAAD is based on the diameter of aortic root, structure of aortic root, and the dissection involvement. For most ATAAD patients, aortic root reinforcement reconstruction is a feasible and safe method.

Gain of Metabolic Benefit with Ablation of miR-149-3p from Subcutaneous Adipose Tissue in Diet-Induced Obese Mice.

The global rise in obesity has become a public health crisis. During the onset of obesity, disrupted catecholamine signals have been described to contribute to excess fat accumulation, however, the molecular and metabolic change of subcutaneous adipose tissue (SAT) upon chronic high-fat feeding has rarely been investigated. Here, we show that chronic high-fat feeding caused a significant decrease in the expression of thermogenic genes and acquisition of partial deleterious features of visceral fat in SAT. Upregulated miR-149-3p was involved in this obesity-induced "visceralization" of SAT via inhibiting PRDM16, a master regulator that promoted SAT thermogenesis. Reduction of miR-149-3p significantly increased PRDM16 expression in SAT, with improved whole-body insulin sensitivity, decreased SAT inflammation, and liver steatosis in high-fat fed mice. These findings provided direct evidence of the anti-obese and anti-diabetic effect of PRDM16 in the obese background for the first time and identified that miR-149-3p could serve as a therapeutic target to protect against diet-induced obesity and metabolic dysfunctions.

The potential atheroprotective role of plant MIR156a as a repressor of monocyte recruitment on inflamed human endothelial cells.

MicroRNAs have become the spotlight of the biological community for more than a decade, but we are only now beginning to understand their functions. The detection of stably expressed endogenous microRNAs in human blood suggests that these circulating miRNAs can mediate intercellular communication. Our previous study reported the surprising finding that exogenous rice MIR168a could regulate liver low-density lipoprotein receptor adapter protein 1 (LDLRAP1) gene expression in mice. Here, we show that plant MIR156a, which is abundantly expressed in dietary green veggies, also stably presents in healthy human serum. Compared with age-matched individuals, decreased levels of MIR156a are observed both in serum and blood vessel of cardiovascular disease (CVD) patients. In vitro studies demonstrate that MIR156a can directly target the junction adhesion molecule-A (JAM-A), which is up-regulated in atherosclerotic lesions from CVD patients. Functional studies show that ectopic expression of MIR156a in human aortic endothelial cells reduces inflammatory cytokine-induced monocytes adhesion by suppressing JAM-A. These findings offer a novel vasoprotective molecular mechanism of green veggies through plant microRNAs.

Characterization of serum miRNAs as molecular biomarkers for acute Stanford type A aortic dissection diagnosis.

Early and convenient diagnosis is urgently needed for acute Stanford type A aortic dissection (AAAD) patients due to its high mortality within the first 48 hours. Circulating microRNAs (miRNAs) are promising biomarkers of cardiovascular diseases, however, little is known about circulating miRNAs involved in AAAD. Here, the blood serum was sampled from 104 AAAD+ patients and 103 age-matched donors. Initial screening was conducted using the TaqMan Low Density Array followed by RT-qPCR confirmation. According to the two-phase selection and validation process, we found that miR-25, miR-29a and miR-155 were significantly elevated, while miR-26b was markedly decreased in AAAD+ serum samples compared with AAAD- individuals. Most importantly, for individuals with hypertension, which is a major contributor to AAAD, the 4-miRNA panel also showed high accuracy in predicting those who are more likely to develop AAAD. In the blind trial set, the panel correctly classified 93.33% AAAD+ patients and 86.67% controls from the hypertension cohort. Finally, the serum miRNA-based biomarker for early AAAD detection was supported by a retrospective analysis. Taken together, we identify a distinct profile of 4-miRNA that can serve as a noninvasive biomarker for AAAD diagnosis, especially for those with hypertension.