Bridging the gap in cardiac mass diagnosis:Advanced imaging,genetic associations,and biomarkers

In this editorial we comment on the article by Huffaker et al published in a recent issue of the World Journal of Clinical Cases.We focus on cardiac tumors linked to genetic syndromes and the differential diagnosis of cardiac masses.As cardiomyocytes lack the ability to actively divide,primary cardiac tumors are extremely rare across all ethnicities and age groups.Once they occur,these tumors are often associated with genetic mutations and,occasionally,genetic syndromes.This underscores the importance of considering genetic mutations and syndromes when encountering these cases.The more common growths in the heart are thrombi and vegetations,which can mimic tumors,further making the differential diagnosis challenging.Among the imaging techniques,contrast-enhanced cardiac magnetic resonance imaging has the highest sensitivity for differential diagnosis.To aid in the differential diagnosis of cardiac masses,especially thrombi,appropriate utilization of biomarkers(i.e.D-dimer level)may provide pivotal clinical implications.Employing a multidisciplinary approach that integrates personal history,epidemiological insights,imaging findings,genetic markers,and biomarkers is therefore critical in the diagnostic process of cardiac masses.

3D printed grafts with gradient structures for organized vascular regeneration

Synthetic vascular grafts suitable for small-diameter arteries(<6 mm) are in great need.However,there are still no commercially available small-diameter vascular grafts(SDVGs) in clinical practice due to thrombosis and stenosis after in vivo implantation.When designing SDVGs,many studies emphasized reendothelization but ignored the importance of reconstruction of the smooth muscle layer(SML).To facilitate rapid SML regeneration,a high-resolution 3D printing method was used to create a novel bilayer SDVG with structures and mechanical properties mimicking natural arteries.Bioinspired by the collagen alignment of SML,the inner layer of the grafts had larger pore sizes and high porosity to accelerate the infiltration of cells and their circumferential alignment,which could facilitate SML reconstruction for compliance restoration and spontaneous endothelialization.The outer layer was designed to induce fibroblast recruitment by low porosity and minor pore size and provide SDVG with sufficient mechanical strength.One month after implantation,the arteries regenerated by 3D-printed grafts exhibited better pulsatility than electrospun grafts,with a compliance(8.9%) approaching that of natural arteries(11.36%) and significantly higher than that of electrospun ones(1.9%).The 3D-printed vascular demonstrated a three-layer structure more closely resembling natural arteries while electrospun grafts showed incomplete endothelium and immature SML.Our study shows the importance of SML reconstruction during vascular graft regeneration and provides an effective strategy to reconstruct blood vessels through 3D-printed structures rapidly.

Segmental radiofrequency ablation of pulmonary vein ostia for patients with refractory paroxysmal atrial fibrillation using multi-slice spiral computed tomography guidance

Objective： To evaluate the safety and clinical efficacy of segmental radiofrequency ablation of pulmonary vein （PV） ostia for patients with refractory paroxysmal atrial fibrillation （AF） under multi-slice spiral computed tomography （MSCT） guidance before the procedure. Methods： A series of 58 consecutive patients with refractory paroxysmal AF were enrolled to undergo segmental radiofrequency ablation ofPV ostia. The 36 male and 22 female patients with mean age of （57.4±9.5） （32-79） years and no obvious organic heart disease. Before ablation, patients received MSCT to generate 3-dimentional image of the left atrium （LA） and proximal PVs. Patients then underwent segmental radiofrequency ablation ofPV ostia using PV circular mapping catheter manipulated several times to ensure complete isolation between PVs and LA. Results： No complications occurred during the procedure. One patient developed delayed cardiac tamponade, which was drained percutaneously. The mean follow-up time was （17.1±9.3） months. Forty-one patients （95%） experienced improved quality of life one month after the procedure. Thirty-six patients （83%） showed stable sinus rhythm, while 10 patients （23%） required additional anti-arrhythmic drugs. AF returned≥1 time in 6 （14%） patients who underwent anti-arrhythmic drug therapy, but the number of episodes was less than that before the procedure. However, one patient experienced recurrent episodes of atrial flutter. Conclusion： It is safe and effective to perform segmental radiofrequency ablation of PV ostia for patients with refractory paroxysmal AF using MSCT guidance mappening.

Association of ABO blood groups with the severity of coronary artery disease: a cross-sectional study

Objective To investigate whether ABO blood groups is associated with the severity of coronary artery disease(CAD). Methods Between January 2015 and December 2017, 1425 first diagnosed CAD patients confirmed by selective coronary angiography were recruited into this cross-sectional study, and their baseline characteristics, ABO blood groups, Gensini score were collected. Multiple linear regression analysis was performed to test the association between the severity of CAD and ABO blood groups. Results The Gensini score was significantly higher in the blood group A than in the non-A groups(41.2 ± 32 vs. 38 ± 27;P = 0.026). After adjusting for age, male, smoking, family history of CAD, hypertension, diabetes mellitus and hypercholesterolemia, multivariate linear regression indicated that blood group A was associated with the severity of CAD(β= 3.298, 95% CI: 0.91–6.505, P = 0.044). In diabetes group, A blood type was also associated with increased Gensini score(P = 0.02) after adjusting for age, male, family history of CAD, hypercholesterolemia, smoking and hypertension. Conclusion In this cross-sectional study, the data indicated that blood group A was an independent risk factor of severity of CAD in Chinese population and Chinese patients with type 2 diabetes.

Effect of a distal protection device on epicardial blood flow and myocardial perfusion in primary percutaneous coronary intervention

Objective: The beneficial effect of percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI) has been well established, but there is the problem of no-reflow phenomenon which is an adverse prognostic factor in primary PCI. In the present study the effect of a distal protection device (PercuSurge GuardWire; GW) on epicardial blood flow and myocardial perfusion was evaluated. Methods and Results: Patients with AMI were randomly divided into 2 groups, the GW and the control groups. The GW group included 52 patients with AMI who underwent primary PCI with GW protection and the control group included 60 patients who underwent primary PCI without GW protection. Epicardial blood flow in the infarct-related artery (IRA) and myocardial perfusion were evaluated according to the thrombolysis in myocardial infarction (TIMI) flow grade and the myocardial blush grade (MBG). We found TIMI score of 3 was obtained significantly more frequently in the GW group (96%) than in the control group (80%). The MBG score of 3 was obtained also significantly greater in the GW group (65%) than in the control group (33%). Conclusion: Primary PCI with GW protection can significantly improve epicardial blood flow and myocardial perfusion.

Prediction of presence and severity of coronary artery disease using prediction for atherosclerotic cardiovascular disease risk in China scoring system

BACKGROUND Coronary artery disease(CAD)is one of the leading causes of death and disease burden in China and worldwide.A practical and reliable prediction scoring system for CAD risk and severity evaluation is urgently needed for primary prevention.AIM To examine whether the prediction for atherosclerotic cardiovascular disease risk in China(China-PAR)scoring system could be used for this purpose.METHODS A total of 6813 consecutive patients who underwent diagnostic coronary angiography were enrolled.The China-PAR score was calculated for each patient and CAD severity was assessed by the Gensini score(GS).RESULTS Correlation analysis demonstrated a significant relationship between China-PAR and GS(r=0.266,P<0.001).In receiver operating characteristic curve analysis,the cut-off values of China-PAR for predicting the presence and the severity of CAD were 7.55%with a sensitivity of 55.8%and specificity of 71.8%[area under the curve(AUC)=0.693,95%confidence interval:0.681 to 0.706,P<0.001],and 7.45%with a sensitivity of 58.8%and specificity of 67.2%(AUC=0.680,95%confidence interval:0.665 to 0.694,P<0.001),respectively.CONCLUSION The China-PAR scoring system may be useful in predicting the presence and severity of CAD.

Validation of the use of foreign gas rebreathing method for non-invasive determination of cardiac output in heart disease patients

Objective: To compare a new device (Innocor) for non-invasive measurement of cardiac output (CO) by foreign gas rebreathing method with conventional techniques used in the measurements of cardiac function. Methods: Cardiac outputs measured by Innocor (CORB) were compared with CO obtained by echocardiography (COEC), Swan-Ganz thermodilution (COTD), and left ventricle radiography (COLVR) in 34 patients subjected to cardiac catheterization. Values obtained from the four methods were analyzed by linear regression and paired values were compared by the method of Bland and Altman in SPSS. Results: There was strong positive correlation (r=0.94) between Innocor cardiac output values and the corresponding values obtained by ther-modilution and between COEC and COLVR values. Thermodilution appears to overestimate cardiac output when compared to the values obtained with Innocor by (0.66±0.22) L/min (P<0.0001). There was no correlation between data obtained by Innocor and the corresponding COEC and COLVR values. Conclusion: Innocor CORB is an easy, safe and well established method for non-invasive measurement of cardiac output with good prospects for clinical application in heart disease patients.

Nomogram for Predicting the Severity of Coronary Artery Disease in Young Adults≤45 Years of Age with Acute Coronary Syndrome

Background:A non-invasive predictive model has not been established to identify the severity of coronary lesions in young adults with acute coronary syndrome(ACS).Methods:In this retrospective study,1088 young adults(≤45 years of age)first diagnosed with ACS who underwent coronary angiography were enrolled and randomized 7:3 into training or testing datasets.To build the nomogram,we determined optimal predictors of coronary lesion severity with the Least Absolute Shrinkage and Selection Operator and Random Forest algorithm.The predictive accuracy of the nomogram was assessed with calibration plots,and performance was assessed with the receiver operating characteristic curve,decision curve analysis and the clinical impact curve.Results:Seven predictors were identified and integrated into the nomogram:age,hypertension,diabetes,body mass index,low-density lipoprotein cholesterol,mean platelet volume and C-reactive protein.Receiver operating characteristic analyses demonstrated the nomogram’s good discriminatory performance in predicting severe coronary artery disease in young patients with ACS in the training(area under the curve 0.683,95%confidence interval[0.645–0.721])and testing(area under the curve 0.670,95%confidence interval[0.611–0.729])datasets.The nomogram was also well-calibrated in both the training(P=0.961)and testing(P=0.302)datasets.Decision curve analysis and the clinical impact curve indicated the model’s good clinical utility.Conclusion:A simple and practical nomogram for predicting coronary artery disease severity in young adults≤45 years of age with ACS was established and validated.

Electrospun fiber membrane with asymmetric NO release for the differential regulation of cell growth

The high incidence of cardiovascular disease has led to significant demand for synthetic vascular grafts in clinical applications.Anti-proliferation drugs are usually loaded into devices to achieve desirable anti-thrombosis effects after implantation.However,the non-selectiveness of these conventional drugs can lead to the failure of blood vessel reconstruction,leading to potential complications in the long term.To address this issue,an asymmetric membrane was constructed through electro-spinning techniques.The bilayer membrane loaded and effectively released nitric oxide(NO),as hoped,from only one side.Due to the short diffusion distance of NO,it exerted negligible effects on the other side of the membrane,thus allowing selective regulation of different cells on both sides.The released NO boosted the growth of endothelial cells(ECs)over smooth muscle cells(SMCs)-while on the side where NO was absent,SMCs grew into multilayers.The overall structure resembled a native blood vessel,with confluent ECs as the inner layer and layers of SMCs to support it.In addition,the membrane preserved the normal function of ECs,and at the same time did not exacerbate inflammatory responses.By preparing this material type that regulates cell behavior differentially,we describe a new method for its application in the cardiovascular field such as for artificial blood vessels.

Comparison of the safety and efficacy of two types of drug-eluting balloons （RESTORE DEB and SeQuent Please） in the treatment of coronary in-stent restenosis： study protocol for a randomized controlled trial （RESTORE ISR China）

1 Introduction In-stent restenosis （ISR）, characterized by neointimal proliferation and/or neoatherosclerosis in the vessel of the stent, can cause a reduction in lumen diameter after stent implantation, which can directly induce the recurrence of angina symptoms or an acute coronary syndrome in patients and is usually life-threatening.

His bundle pacing versus left bundle branch pacing on ventricular function in atrial fibrillation patients referred for pacing:a prospective crossover comparison

BACKGROUND His bundle pacing(HBP)and left bundle branch pacing(LBBP)both provide physiologic pacing which maintain left ventricular synchrony.They both improve heart failure(HF)symptoms in atrial fibrillation(AF)patients.We aimed to assess the intra-patient comparison of ventricular function and remodeling as well as leads parameters corresponding to two pacing modalities in AF patients referred for pacing in intermediate term.METHODS Uncontrolled tachycardia AF patients with both leads implantation successfully were randomized to either modality.Echocardiographic measurements,New York Heart Association(NYHA)classification,quality-of-life assessments and leads parameters were obtained at baseline and at each 6-month follow up.Left ventricular function including the left ventricular endosystolic volume(LVESV),left ventricular ejection fraction(LVEF)and right ventricular(RV)function quantified by tricuspid annular plane systolic excursion(TAPSE)were all assessed.RESULTS Consecutively twenty-eight patients implanted with both HBP and LBBP leads successfully were enrolled(69.1±8.1 years,53.6% male,LVEF 59.2%±13.7%).The LVESV was improved by both pacing modalities in all patients(n=23)and the LVEF was improved in patients with baseline LVEF at less than 50%(n=6).The TAPSE was improved by HBP but not LBBP(n=23).CONCLUSION In this crossover comparison between HBP and LBBP,LBBP was found to have an equivalent effect on LV function and remodeling but better and more stable parameters in AF patients with uncontrolled ventricular rates referred for atrioventricular node(AVN)ablation.HBP could be preferred in patients with reduced TAPSE at baseline rather than LBBP.

Enhanced homing of mesenchymal stem cells for in situ niche remodeling and bone regeneration

Mesenchymal stem cells(MSCs)transplantation is a promising strategy for osteoporosis treatment.However,limited sources and poor tissue-homing efficiency limit their clinical capabilities.In this study,we isolated a kind of MSCs from women’s menstrual blood(MenSCs)noninvasively and established a novel MSCs bone marrow-targeted delivery system by utilizing waterin-oil-in-water droplet microfluidics.MenSCs were encapsulated withinβ-cyclodextrin-functionalized alginate microcapsules loaded with zoledronates,which has a high affinity for bone.With this delivery system,MenSCs could be preferentially delivered to the bone marrow tissues via intravenous infusion,and restored bone mass by remodeling the bone marrow niche in situ in ovariectomized mouse models.Moreover,scRNA-seq analysis demonstrated that those MenSCs homed to the bone marrow recruited CD4^(+)FOXP3^(+)natural regulatory T(nT_(reg))cells by secreting CCL28.The recruited nTreg promoted CD8^(+)T cells to secret Wnt family member 10B(WNT10B),activating the Wnt signaling in osteoblasts and thus promoting bone formation in situ in the bone marrow.This study reveals a promising application of MenSCs in postmenopausal osteoporosis treatment and highlights the clinical value of MenSCs by encouraging women to reserve autologous MenSCs before menopause to prevent and alleviate postmenopausal osteoporosis.

Characterization of ferroptosis-triggered pyroptotic signaling in heart failure

Pressure overload–induced cardiac hypertrophy is a common cause of heart failure(HF),and emerging evidence suggests that excessive oxidized lipids have a detrimental effect on cardiomyocytes.However,the key regulator of lipid toxicity in cardiomyocytes during this pathological process remains unknown.Here,we used lipidomics profiling and RNA-seq analysis and found that phosphatidylethanolamines(PEs)and Acsl4 expression are significantly increased in mice with transverse aortic constriction(TAC)–induced HF compared to sham-operated mice.In addition,we found that overexpressing Acsl4 in cardiomyocytes exacerbates pressure overload‒induced cardiac dysfunction via ferroptosis.Notably,both pharmacological inhibition and genetic deletion of Acsl4 significantly reduced left ventricular chamber size and improved cardiac function in mice with TAC-induced HF.Moreover,silencing Acsl4 expression in cultured neonatal rat ventricular myocytes was sufficient to inhibit hypertrophic stimulus‒induced cell growth.Mechanistically,we found that Acsl4-dependent ferroptosis activates the pyroptotic signaling pathway,which leads to increased production of the proinflammatory cytokine IL-1β,and neutralizing IL-1βimproved cardiac function in Acsl4 transgenic mice following TAC.These results indicate that ACSL4 plays an essential role in the heart during pressure overload‒induced cardiac remodeling via ferroptosis-induced pyroptotic signaling.Together,these findings provide compelling evidence that targeting the ACSL4-ferroptosis-pyroptotic signaling cascade may provide a promising therapeutic strategy for preventing heart failure.

Human bone marrow-derived mesenchymal stem cells transplanted into damaged rabbit heart to improve heart function

Objective: The present study was designed to test whether transplantation of human bone marrow-derived mesen- chymal stem cells (hMSCs) in New Zealand rabbits with myocardial infarction can improve heart function; and whether engrafted donor cells can survive and transdifferentiated into cardiomyocytes. Methods: Twenty milliliters bone marrow was obtained from healthy men by bone biopsy. A gradient centrifugation method was used to separate bone marrow cells (BMCs) and red blood cells. BMCs were incubated for 48 h and then washed with phosphate-buffered saline (PBS). The culture medium was changed twice a week for 28 d. Finally, hematopoietic cells were washed away to leave only MSCs. Human MSCs (hMSCs) were premarked by BrdU 72 h before the transplantation. Thirty-four New Zealand rabbits were randomly divided into myocardial infarction (MI) control group and cell treated group, which received hMSCs (MI+MSCs) through intramyocardial injection, while the control group received the same volume of PBS. Myocardial infarction was induced by ligation of the left coronary artery. Cell treated rabbits were treated with 5×106 MSCs transplanted into the infarcted region after ligation of the coronary artery for 1 h, and the control group received the same volume of PBS. Cyclosporin A (oral solution; 10 mg/kg) was provided alone, 24 h before surgery and once a day after MI for 4 weeks. Echocardiography was measured in each group before the surgery and 4 weeks after the surgery to test heart function change. The hearts were harvested for HE staining and immunohistochemical studies after MI and cell transplantation for 4 weeks. Results: Our data showed that cardiac function was significantly improved by hMSC transplan- tation in rabbit infarcted hearts 4 weeks after MI (ejection fraction: 0.695±0.038 in the cell treated group (n=12) versus 0.554±0.065 in the control group (n=13) (P<0.05). Surviving hMSCs were identified by BrdU positive spots in infarcted region and transdifferentiated into cardiomyocytes characterized with a positive cardiac phenotype: troponin I. Conclusion: Transplan- tation of hMSCs could transdifferentiate into cardiomyocytes and regenerate vascular structures, contributing to functional im- provement.

Optimal time for mesenchymal stem cell transplantation in rats with myocardial infarction

Background:Bone marrow mesenchymal stem cell (MSC) transplantation is a promising strategy in the treatment of myocardial infarction (MI). However, the time for transplanting cells remains controversial. The aim of this study was to find an optimal time point for cell transplantation. Methods: MSCs were isolated and cultured from Sprague-Dawley (SD) rats. MI model was set up in SD rats by permanent ligation of left anterior descending coronary artery. MSCs were directly injected into the infarct border zone at 1 h, 1 week and 2 weeks after MI, respectively. Sham-operated and MI control groups received equal volume of phosphate buffered saline (PBS). At 4 weeks after MI, cardiac function was assessed by echocardiography; vessel density was analyzed on hematoxylin-eosin stained slides by light microscopy; the apoptosis of cardiomyocytes was evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay; the expressions of proteins were analyzed by Western blot. Results: MSC transplantation improved cardiac function, reduced the apoptosis of cardiomyocytes and increased vessel density. These benefits were more obvious in 1-week group than in 1-h and 2-week groups. There are more obvious in-creases in the ratio of bcl-2/bax and the expression of vascular endothelial growth factor (VEGF) and more obvious decreases in the expression of cleaved-caspase-3 in 1-week group than those in other two groups. Conclusion: MSC transplantation was beneficial for the recovery of cardiac function. MSC transplantation at 1 week post-MI exerted the best effects on increases of cardiac function, anti-apoptosis and angiogenesis.

Nine-month angiographic and two-year clinical follow-up of polymer-free sirolimus-eluting stent versus durable-polymer sirolimus-eluting stent for coronary artery disease： the Nano randomized trial

Background First generation drug-eluting stents （DES） were associated with a high incidence of late stent thrombosis （ST）,mainly due to delayed healing and re-endothelization by the durable polymer coating.This study sought to assess the safety and efficacy of the Nano polymer-free sirolimus-eluting stent （SES） in the treatment of patients with de novo coronary artery lesions.Methods The Nano trial is the first randomized trial designed to compare the safety and efficacy of the Nano polymer-free SES and Partner durable-polymer SES （Lepu Medical Technology,Beijing,China） in the treatment of patients with de novo native coronary lesions.The primary endpoint was in-stent late lumen loss （LLL） at 9-month follow-up.The secondary endpoint was major adverse cardiac events （MACE）,a composite of cardiac death,myocardial infarction or target lesion revascularization.Results A total of 291 patients （Nano group：n=143,Partner group：n=148） were enrolled in this trial from 19 Chinese centers.The Nano polymer-free SES was non-inferior to the Partner durable-polymer DES at the primary endpoint of 9 months （P 〈0.001）.The 9-month in-segment LLL of the polymer-free Nano SES was comparable to the Partner SES （0.34±0.42） mm vs.（0.30±0.48） mm,P=0.21）.The incidence of MACE in the Nano group were 7.6% compared to the Partner group of 5.9% （P=0.75） at 2 years follow-up.The frequency of cardiac death and stent thrombosis was low for both Nano and Partner SES （0.8% vs.0.7%,0.8% vs.1.5%,both P=1.00）.Conclusions In this multicenter randomized Nano trial,the Nano polymer-free SES showed similar safety and efficacy compared with the Partner SES in the treatment of patients with de novo coronary artery lesions.Trials in patients with complex lesions and longer term follow-up are necessary to confirm the clinical performance of this novel Nano polymer-free SES.

Novelα-galactosidase A gene mutation in a Chinese Fabry disease family:A case report

BACKGROUND Fabry disease(FD)is a rare X-linked lysosomal storage disease caused by a deficiency of the enzymeα-galactosidase A.CASE SUMMARY Herein,we analyzed a four-generation Chinese family.The proband is a 57-yearold woman who was diagnosed with left ventricular hypertrophy and atrial fibrillation 7 years ago.Echocardiography showed an end-diastolic diameter of the interventricular septum of 19.9 mm,left ventricular end-diastolic diameter of 63.1 mm,and moderate-to-severe mitral regurgitation.Cardiac magnetic resonance indicated an enlarged left heart and right atrium,decreased left ventricular systolic and diastolic function,a left ventricular ejection fraction of 20%,and thickening of the left ventricular septum.In March 2019,gene and enzyme activity tests confirmed the diagnosis of FD.Her son was diagnosed with FD after gene and enzyme activity assay,and was prescribed agalsidase-βfor enzyme replacement therapy in July 2020.Two sisters of the proband were also diagnosed with FD by genetic testing.Both of them had a history of atrial fibrillation.CONCLUSION A novel mutation was identified in a Chinese family with FD,in which the male patient had a low level of enzyme activity,early-onset,and severe organ involvement.Comprehensive analysis of clinical phenotype genetic testing and enzyme activity testing helped in the diagnosis and treatment of this FD family.

Development and material characteristics of glaucoma surgical implants

Background:Glaucoma is the leading cause of irreversible blindness worldwide.The reduction of intraocular pressure has proved to be the only factor which can be modified in the treatment,and surgical management is one of the important methods for the treatment of glaucoma patients.Main text:In order to increase aqueous humor outflow and further reduce intraocular pressure,various drainage implants have been designed and applied in clinical practice.From initial Molteno,Baerveldt and Ahmed glaucoma implants to the Ahmed ClearPath device,Paul glaucoma implant,EX-PRESS and the eyeWatch implant,to iStent,Hydrus,XEN,PreserFlo,Cypass,SOLX Gold Shunt,etc.,glaucoma surgical implants are currently undergoing a massive transformation on their structures and performances.Multitudinous materials have been used to produce these implants,from original silicone and porous polyethylene,to gelatin,stainless steel,SIBS,titanium,nitinol and even 24-carat gold.Moreover,the material geometry,size,rigidity,biocompatibility and mechanism(valved versus nonvalved)among these implants are markedly different.In this review,we discussed the development and material characteristics of both conventional glaucoma drainage devices and more recent implants,such as the eyeWatch and the new minimally invasive glaucoma surgery(MIGS)devices.Conclusions:Although different in design and materials,these delicate glaucoma surgical implants have widely expanded the glaucoma surgical methods,and improved the success rate and safety of glaucoma surgery significantly.However,all of these glaucoma surgical implants have various limitations and should be used for different glaucoma patients at different conditions.

Aiming at early-stage vulnerable plaques:A nanoplatform with dual-mode imaging and lipid-inflammation integrated regulation for atherosclerotic theranostics

The vulnerable plaques in atherosclerosis can cause severe outcome with great danger of acute cardiovascular events.Thus,timely diagnosis and treatment of vulnerable plaques in early stage can effectively benefit the clinical management of atherosclerosis.In this work,a targeting theranostic strategy on early-stage vulnerable plaques in atherosclerosis is realized by a LAID nanoplatform with X-CT and fluorescent dual-mode imaging and lipid-inflammation integrated regulation abilities.The iodinated contrast agents(ICA),phenylboronic acid modified astaxanthin and oxidized-dextran(oxDEX)jointly construct the nanoparticles loaded with the lipid-specific probe LFP.LAID indicates an active targeting to plaques along with the dual-responsive disassembly in oxidative stress and acidic microenvironment of atherosclerosis.The X-CT signals of ICA execute the location of early-stage plaques,while the LFP combines with lipid cores and realizes the recognition of vulnerable plaques.Meanwhile,the treatment based on astaxanthin is performed for restraining the progression of plaques.Transcriptome sequencing suggests that LAID can inhibit the lipid uptake and block NF-κB pathway,which synergistically demonstrates a lipid-inflammation integrated regulation to suppression the plaques growing.The in vivo investigations suggest that LAID delivers a favorable theranostics to the early-stage vulnerable plaques,which provides an impressive prospect for reducing the adverse prognosis of atherosclerosis.

ROS-responsive&scavenging NO nanomedicine for vascular diseases treatment by inhibiting endoplasmic reticulum stress and improving NO bioavailability

Vascular diseases seriously threaten human life and health.Exogenous delivery of nitric oxide(NO)represents an effective approach for maintaining vascular homeostasis during pathological events.However,the overproduction of reactive oxygen species(ROS)at vascular injury sites would react with NO to produce damaging peroxynitrite(ONOO)species and limit the therapeutic effect of NO.Hence,we design a ROS-responsive NO nanomedicine(t-PBA&NO NP)with ROS scavenging ability to solve the dilemma of NO-based therapy.t-PBA&NO NP targets NO and anti-oxidant ethyl caffeate(ECA)to the injury sites via collagen IV homing peptide.The ROS-triggered ROS depletion and ECA release potently alleviate local oxidative stress via ROS scavenging,endoplasmic reticulum and mitochondrial regulation.It subsequently maximizes vascular modulation effects of NO,without production of harmful compounds,reactive nitrogen species(RNS).Therefore,it significantly increases competitiveness of human umbilical vein endothelial cells(HUVECs)over human aortic smooth muscle cells(HASMCs)both in vitro and in vivo.The strategy proved effective in inducing faster re-endothelialization,inhibiting neointimal formation and restoring vascular homeostasis.The synergy between ROS depletion and NO therapy served as a new inspiration for the treatment of cardiovascular diseases and other ROS-associated illnesses.