Accurate Prediction of Retrograde Collateral Channel Crossing in Coronary Artery Chronic Total Occlusion Intervention.

Successful collateral channel (CC) crossing is an essential step in retrograde chronic total occlusion (CTO) percutaneous coronary interventions (PCIs). We previously developed a dedicated CC score based on CC size and tortuosity to facilitate target CC selection. Validation and comparison to other scoring systems were lacking. Thus, the aims of this study were to (1) validate the CC score in a larger independent cohort, and (2) compare its accuracy and clinical usefulness with the J-channel score. All coronary CTO PCIs attempted by experienced high-volume operators from January 2017 to December 2021 were enrolled. The CC and J-channel scores were calculated for all attempted CCs with bi-plane high-resolution cine angiography images. CC crossing success was defined as guidewire reaching the distal true lumen retrogradely. In total, 502 patients who received CTO PCI were included. The retrograde approach was utilized in 244 target CTOs, and a total of 329 CCs were attempted. The overall CC crossing rate was 67.8% (223 of 329) and final technical success rate 92.2% (225 of 244). The average CC score was 2.0 and average J-channel score was 0.71. The sensitivity and specificity of successful CC crossing with the CC score ≥2 were 81.2%, and 84.0%, respectively. Comparison between the CC score (area under the curve 0.87; 95% confidence interval 0.83 to 0.90) and the J-channel score (area under the curve 0.61, 95% confidence interval 0.55 to 0.67) demonstrated superior predictive performance of the CC score (p <0.001). The CC score was an easy-to-use and accurate tool for the prediction of successful CC crossing in retrograde CTO PCI. The CC score can help operators select the ideal target CC, thereby facilitating final procedural success.

Results of streamlining TAVR procedure towards a minimalist approach: a single center experience in Taiwan.

Trans-femoral transcatheter aortic valve replacement (TF-TAVR) performed under conscious sedation (LACS) is not yet become routine practice in Taiwan. We aimed to compared the results between patients received general anesthesia (GA) versus LACS. Our cohort was divided into 3 groups: initial 48 patients received TF-TAVR under routine GA (GA group), subsequent 50 patients under routine LACS (LACS group 1), and recent 125 patients under LACS (LACS group 2). The baseline, procedural characteristics and all outcomes were prospectively collected and retrospectively compared. From Sep 2010 to July 2019, a total of 223 patients were included. The procedure time (157.6 ± 39.4 min vs 131.6 ± 30.3 vs 95.2 ± 40.0, < 0.0001), contrast medium consumption (245.6 ± 92.6 ml vs 207.8 ± 77.9 vs 175.1 ± 64.6, < 0.0001), length of intensive care unit (2 [1-5] days vs 2 [1-3] vs 1 [1-1], P = 0.0001) and hospital stay (9 [7-13] days vs 8 [6-11] vs 6 [5-9], P = 0.0001) decreased significantly with LACS, combined with a trend of less hospital acquired pneumonia (12.5% vs 6.0% vs 5.6%, P = 0.427). 1-year survival rate were also different among 3 groups (83.3% vs 90.0% vs 93.6%, P = 0.053). In our single center experience, a "minimalist" approach of TF-TAVR procedure resulted in less medical resources usage, along with more favorable clinical outcomes.

Quantification of cardiac pumping mechanics in TAVI patients: A pilot study utilizing minimally invasive method for pressure-volume analysis.

The ventriculo-arterial coupling (VAC) and left ventricle (LV) mechanics are crucial and play an important role in the pathophysiology of aortic stenosis (AS). The pressure-volume (PV) analysis is a powerful tool to study VAC and LV mechanics. We proposed a novel minimally-invasive method for PV analysis in patients with severe AS receiving transcatheter aortic valve implantation (TAVI). Patients with severe AS were prospectively enrolled in a single center. LV pressure and cardiac output were recorded before and after TAVI. We constructed the PV loop for analysis by analyzing LV pressure and the assumed flow. 26 patients were included for final analysis. The effective arterial elastance (Ea) decreased after TAVI (3.7 ± 1.3 vs. 2.9 ± 1.1 mmHg/mL, p < 0.0001). The LV end-systolic elastance (Ees) did not change immediately after TAVI (2.4 ± 1.3 vs. 2.6 ± 1.1 mmHg/mL, p = 0.3670). The Ea/Ees improved after TAVI (1.8 ± 0.8 vs. 1.2 ± 0.4, p < 0.0001), demonstrating an immediate improvement of VAC. The stroke work (SW) did not change (7669.6 ± 1913.8 vs. 7626.2 ± 2546.9, p = 0.9330), but the pressure-volume area (PVA) decreased (14469.0 ± 4974.1 vs. 12177.4 ± 4499.9, p = 0.0374) after TAVI. The SW/PVA increased after TAVI (0.55 ± 0.12 vs. 0.63 ± 0.08, p < 0.0001) representing an improvement of LV efficiency. We proposed a novel minimally invasive method for PV analysis in patients with severe AS receiving TAVI. The VAC and LV efficiency improved immediately after TAVI.

A risk stratification model modified from the U.S. guideline could be applied in an Asian population with or without ASCVD.

AIM: This study aimed to evaluate the performance of a modified US (MUS) model for risk prediction of cardiovascular (CV) events in Asian patients and compare it to European and Japanese models. MATERIAL AND METHODS: The MUS model, based on the US ACC/AHA 2018 lipid treatment guideline, was employed to stratify patients under primary or secondary prevention. Two multi-center prospective observational registry cohorts, T-SPARCLE and T-PPARCLE, were used to validate the scoring system, and the primary outcome was the time to first occurrence/recurrence of major adverse cardiac events (MACEs). The MUS model's performance was compared to other models from Europe and Japan. RESULTS: A total of 10,733 patients with the mean age of 64.2 (SD: 11.9) and 36.5% female were followed up for a median of 5.4 years. The MUS model was validated, with an AUC score of 0.73 (95% CI 0.68-0.78). The European and Japanese models had AUC scores ranging from 0.6 to 0.7. The MUS model categorized patients into four distinct CV risk groups, with hazard ratios (HRs) as follows: very high-vs. high-risk group (HR=1.91, 95% CI 1.53-2.39), high-vs. moderate-risk group (HR=2.08, 95% CI 1.60-2.69), and moderate-vs. low-risk group (HR=3.14, 95% CI 1.63-6.03). After adjusting for the MUS model, a history of ASCVD was not a significant predictor of adverse cardiovascular outcomes within each risk group. CONCLUSION: The MUS model is an effective tool for risk stratification in Asian patients with and without ASCVD, accurately predicting MACEs and performing comparably or better than other established risk models. Our findings suggest that patient management should focus on background risk factors instead of solely on primary or secondary prevention.

Association of Major Adverse Cardiac Events and Beta-Blockers in Patients with and without Atherosclerotic Cardiovascular Disease: Long-Term Follow-Up Results of the T-SPARCLE and T-PPARCLE Registry in Taiwan.

Beta-blockers are widely used, but the benefit is now challenged in patients at risk of atherosclerotic cardiovascular disease (ASCVD) in the present coronary reperfusion era. We aimed to identify the risk factors of a major adverse cardiac event (MACE) and the long-term effect of beta-blockers in two large cohorts in Taiwan. Two prospective observational cohorts, including patients with known atherosclerosis cardiovascular disease (T-SPARCLE) and patients with at least one risk factor of ASCVD but without clinically evident ASCVD (T-PPARCLE), were conducted in Taiwan. The primary endpoint is the time of first occurrence of a MACE (cardiovascular death, nonfatal stroke, nonfatal myocardial infarction, and cardiac arrest with resuscitation). Between December 2009 and November 2014, with a median 2.4 years follow-up, 11,747 eligible patients (6921 and 4826 in T-SPARCLE and T-PPARCLE, respectively) were enrolled. Among them, 273 patients (2.3%) met the primary endpoint. With multivariate Cox PH model analysis, usage of beta-blocker was lower in patients with MACE (42.9% vs. 52.4%, p < 0.01). In patients with ASCVD, beta-blocker usage was associated with lower MACEs (hazard ratio 0.72; p < 0.001), but not in patients without ASCVD. The event-free survival of beta-blocker users remained higher during the follow-up period (p < 0.005) of ASCVD patients. In conclusion, in ASCVD patients, reduced MACE was associated with beta-blocker usage, and the effect was maintained during a six-year follow-up. Prescribing beta-blockers as secondary prevention is reasonable in the Taiwanese population.

On-Table Catheter-Based Neurosalvage Performed by Cardiologists for Embolic Complication during an Endovascular Procedure.

Objectives: To report our experience and clinical results of neurosalvage techniques, performed by interventional cardiologists without moving the patient, to manage cerebral thromboembolic complications. Background: Iatrogenic emboli may be released during an endovascular procedure, causing permanent neurological complications and catastrophic outcomes. Methods: Between July 2013 and December 2017, a total of eight patients suffered from embolic complications during endovascular procedures (two radiofrequency catheter ablation, five coronary angiogram/angioplasty, and one subclavian artery angioplasty). Catheter-based neurosalvage was attempted by experienced interventional cardiologists promptly in the same catheterization room. Results: The embolized locations were the M1 segment of the middle cerebral artery in four patients, the M2/M3 segments in three, and the basilar artery in one. Access to the supra-aortic vessels was achieved. Local intra-arterial thrombolysis was given in five patients (63%) and balloon angioplasty in three (38%). Intra-arterial thrombectomy with a stent retriever was attempted in three patients but failed in one. A combination of different techniques was used in three patients (38%). Final thrombolysis in cerebral infarction grade 3 flow was achieved in seven patients (88%). Favorable clinical outcomes at 1-month follow-up (modified Rankin scale of 0-2) were observed in seven patients (88%), and none of the patients had died at 12 months. Conclusions: Our experience demonstrated that acute embolic complications during an endovascular procedure can be salvaged by interventional cardiologists with acceptable angiographic and clinical results.

The novel role of ER protein TXNDC5 in the pathogenesis of organ fibrosis: mechanistic insights and therapeutic implications.

Fibrosis-related disorders account for an enormous burden of disease-associated morbidity and mortality worldwide. Fibrosis is defined by excessive extracellular matrix deposition at fibrotic foci in the organ tissue following injury, resulting in abnormal architecture, impaired function and ultimately, organ failure. To date, there lacks effective pharmacological therapy to target fibrosis per se, highlighting the urgent need to identify novel drug targets against organ fibrosis. Recently, we have discovered the critical role of a fibroblasts-enriched endoplasmic reticulum protein disulfide isomerase (PDI), thioredoxin domain containing 5 (TXNDC5), in cardiac, pulmonary, renal and liver fibrosis, showing TXNDC5 is required for the activation of fibrogenic transforming growth factor-ß signaling cascades depending on its catalytic activity as a PDI. Moreover, deletion of TXNDC5 in fibroblasts ameliorates organ fibrosis and preserves organ function by inhibiting myofibroblasts activation, proliferation and extracellular matrix production. In this review, we detailed the molecular and cellular mechanisms by which TXNDC5 promotes fibrogenesis in various tissue types and summarized potential therapeutic strategies targeting TXNDC5 to treat organ fibrosis.

Detection of Carotid Artery Stenosis Based on Video Motion Analysis for Fast Screening.

Background Carotid artery stenosis (CAS) is a common cause of ischemic stroke, and the early detection of CAS may improve patient outcomes. Carotid Doppler ultrasound is commonly used to diagnose CAS. However, it is costly and may not be practical for regular screening practice. This article presents a novel noninvasive and noncontact detection technique using video-based motion analysis (VMA) to extract useful information from subtle pulses on the skin surface to screen for CAS. Methods and Results We prospectively enrolled 202 patients with prior carotid Doppler ultrasound data. A short 30-second video clip of the neck was taken using a commercial mobile device and analyzed by VMA with mathematical quantification of the amplitude of skin motion changes in a blinded manner. The first 40 subjects were used to set up the VMA protocol and define cutoff values, and the following 162 subjects were used for validation. Overall, 54% of the 202 subjects had ultrasound-confirmed CAS. Using receiver operating characteristic curve analysis, the area under the curve of VMA-derived discrepancy values to differentiate patients with and without CAS was excellent (area under the curve, 0.914 [95% CI, 0.874-0.954]; P<0.01). The best cutoff value of VMA-derived discrepancy values to screen for CAS was 5.1, with a sensitivity of 87% and a specificity of 87%. The diagnostic accuracy was consistently high in different subject subgroups. Conclusions A simple and accurate screening technique to quickly screen for CAS using a VMA system is feasible, with acceptable sensitivity and specificity.

Serial neurocognitive changes following transcatheter aortic valve replacement: comparison between low and intermediate-high risk groups.

BACKGROUND: Data comparing the neurocognitive trajectory between low and intermediate-high risk patients following transcatheter aortic valve replacement (TAVR) is never reported. AIMS: To report serial neurocognitive changes up to 1 year post-TAVR in low and intermediate-high risk groups as well as overall cohort. METHODS: Prospective neurological assessments (NIHSS and Barthel Index), global cognitive tests (MMSE and Alzheimer Disease Assessment Scale-Cognitive Subtest, ADAS-cog) and executive performances (Color Trail Test A and B and verbal fluency), were applied at baseline, 3 months and 1 year post-TAVR. RESULTS: In overall cohort, persistent improvement to 1 year in MMSE, ADAS-cog, Color Trail Test A and B was found. According to the STS score, the study cohort was divided into low (<4%, N = 81) and intermediate-high (≧4%, N = 75) risk groups. The baseline neurologic and cognitive performance was significantly worse in intermediate-high risk group. Slight improvement on general neurological functions (Barthel index and proportion of NIHSS>0 patients) at 1 year could be observed only in intermediate-high risk group. In global cognitive assessments, improvement in MMSE and ADAS-cog at 1 year was found in both groups, but the proportion of cognitive improvement was more obvious in intermediate-high risk group. In Color Trail Tests and verbal fluency, significant and persistent improvement up to 1 year could be observed only in low risk group. CONCLUSIONS: TAVR was associated with persistent improvement in global cognitive function, as well as in attention and psychomotor processing speed, up to 1 year in overall cohort. However, improvement in tests for executive functions can only be seen in low risk group.

Comparison between drug-coated balloons and drug-eluting stents in very small coronary artery interventions.

The optimal management of very small vessel (reference diameter from 2.0 to 2.25 mm) in percutaneous coronary interventions (PCIs) is controversial. We aimed to compare the efficacy and safety of drug-coated balloons (DCBs) and drug-eluting stents (DESs) for de-novo very small vessel interventions. We conducted a retrospective analysis of consecutive patients who received very small vessel PCI with a DCB or DES between January 2018 and March 2021. The outcome measures were the incidence of ischemia-driven target lesion revascularization (TLR) and major adverse cardiac and cerebrovascular events (MACCEs) within 1 year after PCI. MACCEs were defined as the composite of ischemia-driven TLR, all-cause death, non-fatal acute coronary syndrome, stroke, or heart failure requiring hospitalization. A total of 205 patients undergoing PCI with a DCB or DES were enrolled in this study. The procedural complication rate was 2.5% in the DES group and 1.7% in the DCB group (P = 1.000). After 1-year of follow-up, the cumulative incidence of TLR was 7.2% in the DCB group and 4.9% in the DES group (P = 0.530). The cumulative incidence of MACCEs was 10.6% in the DCB group and 12.7% in the DES group (P = 0.769). Only female gender, acute coronary syndrome on presentation, and dual antiplatelet therapy duration < 3 months were significantly associated with MACCEs at 1 year, but the use of DCB or DES was not. The use of DCBs or DESs in de novo very small vessel intervention was not associated with different outcomes at 1 year.

Conus branch artery utilization in percutaneous coronary intervention for chronic total occlusion.

Data on the prevalence of conus branch artery (CBA) is scarce, and its utilization in percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) is non-existing. The present study examined carefully in a large cohort the angiographic prevalence of CBA, its role as a collateral channel for the occlusion, and the potential usage of CBA in contemporary CTO PCI. We retrospectively examined consecutive CTO PCIs from our database between 2016 and 2019. All CTO PCIs were evaluated and the results with complications were recorded to determine the prevalence and utilization of CBA. From January 2016 to December 2019, a total of 556 CTO PCI attempts in 546 patients by high-volume operators were enrolled. The clinical, angiographic, and procedural details were collected. CBA was identifiable in 85.3% of these patients, and CBA providing visible collaterals connected to CTO distal lumen was found in 27.8% of patients. 84 CBA were used for balloon anchoring, 17 for selective distal true lumen visualization, and 9 as actual retrograde interventional collateral channel during CTO PCI. Only 1 patient suffered from chest pain during CBA balloon anchoring, and no other procedural complication such as arrhythmia or perforation occurred.CBA is frequently seen in coronary CTO. Its existence provided potential for various CTO PCI technique applications, without increase in risk.

Cannabinoid receptor 1 antagonist genistein attenuates marijuana-induced vascular inflammation.

Epidemiological studies reveal that marijuana increases the risk of cardiovascular disease (CVD); however, little is known about the mechanism. Δ9-tetrahydrocannabinol (Δ9-THC), the psychoactive component of marijuana, binds to cannabinoid receptor 1 (CB1/CNR1) in the vasculature and is implicated in CVD. A UK Biobank analysis found that cannabis was an risk factor for CVD. We found that marijuana smoking activated inflammatory cytokines implicated in CVD. In silico virtual screening identified genistein, a soybean isoflavone, as a putative CB1 antagonist. Human-induced pluripotent stem cell-derived endothelial cells were used to model Δ9-THC-induced inflammation and oxidative stress via NF-κB signaling. Knockdown of the CB1 receptor with siRNA, CRISPR interference, and genistein attenuated the effects of Δ9-THC. In mice, genistein blocked Δ9-THC-induced endothelial dysfunction in wire myograph, reduced atherosclerotic plaque, and had minimal penetration of the central nervous system. Genistein is a CB1 antagonist that attenuates Δ9-THC-induced atherosclerosis.

Targeting mechanosensitive endothelial TXNDC5 to stabilize eNOS and reduce atherosclerosis in vivo.

Although atherosclerosis preferentially develops at arterial curvatures and bifurcations where disturbed flow (DF) activates endothelium, therapies targeting flow-dependent mechanosensing pathways in the vasculature are unavailable. Here, we provided experimental evidence demonstrating a previously unidentified causal role of DF-induced endothelial TXNDC5 (thioredoxin domain containing 5) in atherosclerosis. TXNDC5 was increased in human and mouse atherosclerotic lesions and induced in endothelium subjected to DF. Endothelium-specific Txndc5 deletion markedly reduced atherosclerosis in ApoE-/- mice. Mechanistically, DF-induced TXNDC5 increases proteasome-mediated degradation of heat shock factor 1, leading to reduced heat shock protein 90 and accelerated eNOS (endothelial nitric oxide synthase) protein degradation. Moreover, nanoparticles formulated to deliver Txndc5-targeting CRISPR-Cas9 plasmids driven by an endothelium-specific promoter (CDH5) significantly increase eNOS protein and reduce atherosclerosis in ApoE-/- mice. These results delineate a new molecular paradigm that DF-induced endothelial TXNDC5 promotes atherosclerosis and establish a proof of concept of targeting endothelial mechanosensitive pathways in vivo against atherosclerosis.

Targeted polyelectrolyte complex micelles treat vascular complications in vivo.

Vascular disease is a leading cause of morbidity and mortality in the United States and globally. Pathological vascular remodeling, such as atherosclerosis and stenosis, largely develop at arterial sites of curvature, branching, and bifurcation, where disturbed blood flow activates vascular endothelium. Current pharmacological treatments of vascular complications principally target systemic risk factors. Improvements are needed. We previously devised a targeted polyelectrolyte complex micelle to deliver therapeutic nucleotides to inflamed endothelium in vitro by displaying the peptide VHPKQHR targeting vascular cell adhesion molecule 1 (VCAM-1) on the periphery of the micelle. This paper explores whether this targeted nanomedicine strategy effectively treats vascular complications in vivo. Disturbed flow-induced microRNA-92a (miR-92a) has been linked to endothelial dysfunction. We have engineered a transgenic line (miR-92aEC-TG /Apoe-/- ) establishing that selective miR-92a overexpression in adult vascular endothelium causally promotes atherosclerosis in Apoe-/- mice. We tested the therapeutic effectiveness of the VCAM-1-targeting polyelectrolyte complex micelles to deliver miR-92a inhibitors and treat pathological vascular remodeling in vivo. VCAM-1-targeting micelles preferentially delivered miRNA inhibitors to inflamed endothelial cells in vitro and in vivo. The therapeutic effectiveness of anti-miR-92a therapy in treating atherosclerosis and stenosis in Apoe-/- mice is markedly enhanced by the VCAM-1-targeting polyelectrolyte complex micelles. These results demonstrate a proof of concept to devise polyelectrolyte complex micelle-based targeted nanomedicine approaches treating vascular complications in vivo.

The periprocedural and 30-day outcomes of carotid stenting in patients with carotid artery near-occlusion.

The safety of endovascular revascularization in patients with carotid artery near occlusion (CANO) is unknown. We aimed to evaluate the peri-procedural risk in CANO patients receiving carotid artery stenting (CAS). A prospective data base with retrospective review was performed to identify patients who underwent CAS with CANO from July 2006 to July 2020, and had at least 1-month clinical follow-up data. The primary endpoints were stroke, hyperperfusion syndrome, and death within 30 days after CAS. A total of 198 patients with carotid artery stenosis were enrolled including 92 patients with CANO and 106 age and sex-matched patients with 70-99% conventional carotid stenosis. Full distal carotid collapse was found in 45 CANO patients (45/92, 49%). The technical success rate was 100%. The CANO patients had significantly longer lesion lengths compared with those of the non-CANO group. The incidence of hyperperfusion syndrome was comparable (CANO: 2.2%, non-CANO: 0.9%, P = 0.598). The risks of ischemic stroke and death within 30 days were 1.1% and 0% in the CANO group; and 1.9% and 0.9%, in the non-CANO group, respectively, without statistical difference. In conclusion, CAS is safe for patients with CANO, with a similar low 30-day peri-procedural event rate comparable to those of non-CANO.

Mechanotransduction in fibrosis: Mechanisms and treatment targets.

To perceive and integrate the environmental cues, cells and tissues sense and interpret various physical forces like shear, tensile, and compression stress. Mechanotransduction involves the sensing and translation of mechanical forces into biochemical and mechanical signals to guide cell fate and achieve tissue homeostasis. Disruption of this mechanical homeostasis by tissue injury elicits multiple cellular responses leading to pathological matrix deposition and tissue stiffening, and consequent evolution toward pro-inflammatory/pro-fibrotic phenotypes, leading to tissue/organ fibrosis. This review focuses on the molecular mechanisms linking mechanotransduction to fibrosis and uncovers the potential therapeutic targets to halt or resolve fibrosis.

Impact of conduction disturbances on left ventricular mass regression and geometry change following transcatheter aortic valve replacement.

Our study aimed to compare the difference of LV mass regression and remodeling in regard of conduction disturbances (CD) following transcatheter aortic valve replacement (TAVR). A prospective analysis of 152 consecutive TAVR patients was performed. 53 patients (34.9%) had CD following TAVR, including 30 (19.7%) permanent pacemaker implantation and 23 (15.2%) new left bundle branch block. In 123 patients with 1-year follow-up, significant improvement of LV ejection fraction (LVEF) (baseline vs 12-month: 65.1 ± 13.2 vs 68.7 ± 9.1, P = 0.017) and reduced LV end-systolic volume (LVESV) (39.8 ± 25.8 vs 34.3 ± 17.1, P = 0.011) was found in non-CD group (N = 85), but not in CD group (N = 38). Both groups had significant decrease in LV mass index (baseline vs 12-month: 148.6 ± 36.9 vs. 136.4 ± 34.7 in CD group, p = 0.023; 153.0 ± 50.5 vs. 125.6 ± 35.1 in non-CD group, p < 0.0001). In 46 patients with 3-year follow-up, only non-CD patients (N = 28) had statistically significant decrease in LV mass index (Baseline vs 36-month: 180.8 ± 58.8 vs 129.8 ± 39.1, p = 0.0001). Our study showed the improvement of LV systolic function, reduced LVESV and LV mass regression at 1 year could be observed in patients without CD after TAVR. Sustained LV mass regression within 3-year was found only in patients without CD.

Single-cell metabolic imaging reveals a SLC2A3-dependent glycolytic burst in motile endothelial cells.

Single-cell motility is spatially heterogeneous and driven by metabolic energy. Directly linking cell motility to cell metabolism is technically challenging but biologically important. Here, we use single-cell metabolic imaging to measure glycolysis in individual endothelial cells with genetically encoded biosensors capable of deciphering metabolic heterogeneity at subcellular resolution. We show that cellular glycolysis fuels endothelial activation, migration and contraction and that sites of high lactate production colocalize with active cytoskeletal remodelling within an endothelial cell. Mechanistically, RhoA induces endothelial glycolysis for the phosphorylation of cofilin and myosin light chain in order to reorganize the cytoskeleton and thus control cell motility; RhoA activation triggers a glycolytic burst through the translocation of the glucose transporter SLC2A3/GLUT3 to fuel the cellular contractile machinery, as demonstrated across multiple endothelial cell types. Our data indicate that Rho-GTPase signalling coordinates energy metabolism with cytoskeleton remodelling to regulate endothelial cell motility.

Mutual Interplay of Host Immune System and Gut Microbiota in the Immunopathology of Atherosclerosis.

Inflammation is the key for the initiation and progression of atherosclerosis. Accumulating evidence has revealed that an altered gut microbiome (dysbiosis) triggers both local and systemic inflammation to cause chronic inflammatory diseases, including atherosclerosis. There have been some microbiome-relevant pro-inflammatory mechanisms proposed to link the relationships between dysbiosis and atherosclerosis such as gut permeability disruption, trigger of innate immunity from lipopolysaccharide (LPS), and generation of proatherogenic metabolites, such as trimethylamine N-oxide (TMAO). Meanwhile, immune responses, such as inflammasome activation and cytokine production, could reshape both composition and function of the microbiota. In fact, the immune system delicately modulates the interplay between microbiota and atherogenesis. Recent clinical trials have suggested the potential of immunomodulation as a treatment strategy of atherosclerosis. Here in this review, we present current knowledge regarding to the roles of microbiota in contributing atherosclerotic pathogenesis and highlight translational perspectives by discussing the mutual interplay between microbiota and immune system on atherogenesis.