Ultrasound-mediated HGF Gene Microbubbles Mitigate Hyperkinetic Pulmonary Arterial Hypertension in Rabbits.

AIM: Hyperkinetic pulmonary arterial hypertension (PAH) is a complication of congenital heart disease. Gene therapy is a new experimental treatment for PAH, and ultrasound-mediated gene-carrying microbubble targeted delivery is a promising development for gene transfer. METHODS: This study successfully established a hyperkinetic PAH rabbit model by a common carotid artery and jugular vein shunt using the cuff style method. Liposome microbubbles carrying the hepatocyte growth factor (HGF) gene were successfully constructed. An in vitro experiment evaluated the appropriate intensity of ultrasonic radiation by Western blots and 3H-TdR incorporation assays. In an in vivo experiment, after transfection of ultrasound-mediated HGF gene microbubbles, catheterisation was applied to collect haemodynamic data. Hypertrophy of the right ventricle was evaluated by measuring the right ventricle hypertrophy index. Western blot and immunohistochemistry analyses were used to detect the expression of human (h)HGF and angiogenic effects, respectively. RESULTS: The most appropriate ultrasonic radiation intensity was 1.0 W/cm2 for 5 minutes. Two weeks after transfection, both systolic pulmonary arterial pressure and mean pulmonary arterial pressure were attenuated. Hypertrophy of the right ventricle was reversed. hHGF was transplanted into the rabbits, resulting in a high expression of hHGF protein and an increase in the number of small pulmonary arteries. Ultrasound-mediated HGF gene microbubble therapy was more effective at attenuating PAH and increasing the density of small pulmonary arteries than single HGF plasmid transfection. CONCLUSIONS: Ultrasound-mediated HGF gene microbubbles significantly improved the target of gene therapy in a rabbit PAH model and enhanced the tropism and transfection rates. Thus, the technique can effectively promote small pulmonary angiogenesis and play a role in the treatment of PAH without adverse reactions.

Anomalous Double Blood Supply to the Anterior Descending (LAD, RAD) Artery in an Infective Endocarditis Patient: A Case Report.

BACKGROUND: Double blood supply to the anterior descending artery is a rare finding of coronary angiography. However, infective endocarditis (IE) combined with anomalous double blood supply to the anterior descending artery has not been reported. CASE PRESENTATION: A 58-year-old male previously diagnosed with IE came to the emergency department with complaints of chest tightness and dyspnea. Further examination confirmed severe aortic valve regurgitation combined with IE and anomalous double blood supply to the anterior descending artery. The cardiopulmonary bypass surgery was performed by direct perfusion through the normal left and right coronary openings. After surgery, the heart started beating again normally without any cardiogenic ischemic events. CONCLUSION: Cardiopulmonary bypass by direct perfusion was safe in the patient with anomalous double blood supply to the anterior descending artery.

Mitral valve regurgitation and endocarditis triggered by a needle.

BACKGROUND: Cardiac foreign bodies are extremely rare in clinical patients, especially when foreign bodies damage the internal structure of the heart coincidentally after they penetrate the heart. CASE PRESENTATION: Here, we report the case of a two-year-old girl whose heart was penetrated by a needle, which triggered mitral valve regurgitation and endocarditis. After a comprehensive inspection, accurate judgment and surgical preparation, we removed the needle and repaired her mitral valve. Fortunately, she recovered postoperatively. CONCLUSION: From this case, we can know that when cardiac foreign bodies are suspected, ultrasound is an important inspection method. Moreover, the approaches for handling each such case are different depending on the associated injuries.

Lethal giant larvae 1 inhibits smooth muscle calcification via high mobility group box 1.

Vascular calcification is a pathological process closely related to atherosclerosis, diabetic vascular diseases, vascular injury, hypertension, chronic kidney disease and aging. Lethal giant larvae 1 (LGL1) is known as a key regulator of cell polarity and plays an important role in tumorigenesis. However, whether LGL1 regulates vascular calcification remains unclear. In this study, we generated smooth muscle-specific LGL1 knockout (LGL1SMKO) mice by cross-breeding LGL1flox/flox mice with α-SMA-Cre mice. LGL1 level was significantly decreased during calcifying conditions. Overexpression of LGL1 restrained high phosphate-induced calcification in vascular smooth muscle cells (VSMCs). Mechanically, LGL1 could bind with high mobility group box 1 (HMGB1) and promote its degradation via the lysosomal pathway, thereby inhibiting calcification. Smooth muscle-specific deletion of LGL1 increased HMGB1 level and aggravated vitamin D3-induced vascular calcification, which was attenuated by an HMGB1 inhibitor. LGL1 may inhibit vascular calcification by preventing osteogenic differentiation via promoting HMGB1 degradation.

Knockdown of miR-665 Protects Against Cardiomyocyte Ischemia/Reperfusion Injury-Induced ROS Accumulation and Apoptosis Through the Activation of Pak1/Akt Signaling in Myocardial Infarction.

Myocardial infarction (MI) is one of the major causes of death worldwide, and the therapeutic strategies of MI are still limited. In this study, we investigated the function of miR-665 in MI. In the present study, an ischemia/reperfusion (I/R) rat model and a hypoxia/reoxygenation (H/R)-induced H9c2 cell model were successfully established to mimic the MI for in vivo and in vitro studies. The concentrations of lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), tumor necrosis factor alpha (TNF-α), IL-6, and reactive oxygen species (ROS) were then measured. Moreover, cell viability and apoptosis were detected by MTT assay, TdT-mediated dUTP nick end labeling (TUNEL), and PI/FITC-annexin V assay. The binding of miR-665 and Pak1 was determined by luciferase assay. miR-665 was upregulated in I/R rats, and the overexpression of miR-665 significantly increased LDH, CK-MB, TNF-α, IL-6, and ROS concentrations and induced cell apoptosis, while knockdown of miR-665 had opposite results. Consistent with in vivo results, miR-665 induced cell apoptosis and ROS generation in H/R-treated H9c2 cells. More importantly, Pak1 was the target gene of miR-665, and knockdown of miR-665 depressed the accumulation of ROS and cell apoptosis by targeting Pak1 and promoting the phosphorylation of Akt, whereas knockdown of Pak1 could attenuate the protection of miR-665 inhibitor in H/R-treated H9c2 cells. Therefore, knockdown of miR-665 protects against cardiomyocyte ischemia/reperfusion injury-induced ROS accumulation and apoptosis through activating Pak1/Akt signaling in MI. In general, understanding the biology and modulation of miR-665 may have the potential to counteract the development of MI.

Nicotine induces endothelial dysfunction and promotes atherosclerosis via GTPCH1.

Smoking is a major preventable risk factor for atherosclerosis. However, the causative link between cigarette smoke and atherosclerosis remains to be established. The objective of this study is to characterize the role of GTP cyclohydrolase 1 (GTPCH1), the rate-limiting enzyme for de novo tetrahydrobiopterin (BH4) synthesis, in the smoking-accelerated atherosclerosis and the mechanism involved. In vitro, human umbilical vein endothelial cells were treated with nicotine, a major component of cigarette smoke, which reduced the mRNA and protein levels of GTPCH1 and led to endothelial dysfunction. GTPCH1 overexpression or sepiapterin could attenuate nicotine-reduced nitric oxide and -increased reactive oxygen species levels. Mechanistically, human antigen R (HuR) bound with the adenylateuridylate-rich elements of the GTPCH1 3' untranslated region and increased its stability; nicotine inhibited HuR translocation from the nucleus to cytosol, which downregulated GTPCH1. In vivo, nicotine induced endothelial dysfunction and promoted atherosclerosis in ApoE-/- mice, which were attenuated by GTPCH1 overexpression or BH4 supplement. Our findings may provide a novel and promising approach to atherosclerosis treatment.

Bone morphogenetic protein 7-transduced human dermal-derived fibroblast cells differentiate into osteoblasts and form bone in vivo.

BACKGROUND: Human dermal-derived fibroblast cells (hDDFCs) are multipotent. Bone morphogenetic proteins (BMPs) are a group of cytokines that promote different developmental processes, including the formation of bone. BMPs can promote hDDFC osteogenesis, but the role of BMP7 in hDDFC osteogenesis in vitro and bone formation in vivo has not been investigated in depth. MATERIALS AND METHODS: hDDFCs were stably transfected with a human BMP7 recombinant adenovirus and osteogenic differentiation was examined by alkaline phosphatase staining and calcium accumulation. In addition, we measured the expression of osteoblast-related genes. To examine osteogenesis in vivo, we injected C57BL/6 nude mice with adenovirus-transfected hDDFCs in a calcium alginate hydrogel and examined bone formation using soft X-ray, histological, and immunohistochemical analyses. RESULTS: Our findings showed that adenovirus-mediated BMP7 expression promoted osteogenic differentiation of hDDFCs and enhanced expression of osteoblast-related genes in vitro. Cells infected with BMP7 adenoviruses showed enhanced bone formation and osteoblast-related gene expression in vivo after the injection of hDDFC-hydrogel mixture. CONCLUSIONS: Taken together, our data indicate that BMP7 significantly promotes hDDFC osteogenesis, and confirm that infecting hDDFCs with BMP7-expressing adenoviruses is a useful tool for bone tissue engineering.

Incidence and Risk Factors of Delirium in Patients After Type-A Aortic Dissection Surgery.

OBJECTIVE: To study the incidence and related risk factors for postoperative delirium after type-A aortic dissection in patients who underwent Sun's procedure (total arch replacement using a tetrafurcate graft with stented elephant trunk implantation). DESIGN: A retrospective study. SETTING: A cardiac surgical intensive care unit. PARTICIPANTS: The study comprised 100 patients admitted to the intensive care unit for type-A aortic dissection. INTERVENTIONS: All patients underwent Sun's procedure with uniform preoperative and anesthetic treatment. MEASUREMENTS AND MAIN RESULTS: Delirium was evaluated using the Confusion Assessment Method for the intensive care unit. Baseline demographics and preoperative, intraoperative, and postoperative data were recorded and analyzed retrospectively via univariate analysis and multivariate logistic regression. The incidence of postoperative delirium was 34%, according to Confusion Assessment Method for the intensive care unit criteria. Univariate analysis revealed that 17 variables differed significantly among patients with and without delirium. Additional multivariate stepwise logistic regression analysis confirmed that cerebrovascular disease history, surgery duration, cardiopulmonary bypass duration, intubation time, and hypoxia were strongly associated with postoperative delirium. CONCLUSIONS: Delirium is a common postoperative complication of aortic dissection. Cerebrovascular disease history, surgery and cardiopulmonary bypass duration, postoperative hypoxia, and intubation time are independently associated with the development of delirium. Early diagnosis of delirium and modifying these factors properly may be helpful to improve patients' prognosis.

Ethyl pyruvate ameliorates monocrotaline-induced pulmonary arterial hypertension in rats.

BACKGROUND: Ethyl pyruvate (EP) is an anti-inflammatory and anti-oxidant agent associated with many diseases. In this study, we evaluated whether EP could attenuate monocrotaline-induced pulmonary arterial hypertension (PAH). METHODS: A PAH model was established by subcutaneously injecting a single dose of monocrotaline (60 mg/kg). And then a daily intraperitoneal injection of EP (50 mg/kg) was administered on day 1 to day 28 (preventive EP treatment) or day 15 to day 28 (therapeutic EP treatment). Hemodynamic changes were measured by catheterization, and the right ventricle hypertrophy index, the medial wall thickness, and the medial wall areas were also calculated. Enzyme-linked immunosorbent assay and immunohistochemical analysis were used to determine the serum levels and expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and endothelin-1 (ET-1) in the lung tissue. RESULTS: Both preventive and therapeutic EP treatment significantly ameliorated hemodynamic changes and vascular remodeling indicators (all P < 0.05). The serum levels and expression of TNF-α, IL-6, and ET-1 in the lung tissue were also significantly decreased (all P < 0.05). CONCLUSIONS: EP ameliorates monocrotaline-induced PAH and reverses pulmonary vascular remolding in rats by inhibiting the release of TNF-α and IL-6 and reducing the expression of ET-1.

A Mendelian randomization-based study of the causal relationship between leisure sedentary behavior and delirium.

BACKGROUND: Delirium is an acute or subacute change in mental status caused by various factors. We evaluated the causal relationship between leisure sedentary behaviors (LSBs) and delirium. METHODS: A two-sample Mendelian randomization (MR) study was performed to evaluate the causal relationship between sedentary behaviors (time spent watching television, time spent using computer, and time spent driving) and delirium. Statistical information for the associations between single nucleotide polymorphisms (SNPs) and the traits of interest was obtained from independent consortia that focused on European populations. The dataset for LSBs was acquired from genome-wide association studies (GWAS) comprising a substantial sample size: 437887 samples for time spent watching television, 360,895 for time spent using computer, and 310,555 for time spent driving. A GWAS with 1269 delirium cases and 209,487 controls was used to identify genetic variation underlying the time of LSBs. We used five complementary MR methods, including inverse variance weighted method (IVW), MR-Egger, weighted median, weighted mode, and simple mode. RESULTS: Genetically predicted time spent watching television (odds ratio [OR]: 2.921, 95 % confidence interval [CI]: 1.381-6.179) demonstrated significant association with delirium (P = 0.005), whereas no significant associations were observed between time spent using computer (OR: 0.556, 95 % CI: 0.246-1.257, P = 0.158) and time spent driving (OR: 1.747, 95 % CI: 0.09-3. 40, P = 0.713) and delirium. Sensitivity analyses supported a causal interpretation, with limited evidence of significant bias from genetic pleiotropy. Moreover, our MR assumptions appeared to be upheld, enhancing the credibility of our conclusions. LIMITATIONS: Larger sample sizes are needed to validate the findings of our study. CONCLUSION: Time spent watching television is a significant risk factor for delirium. Reducing television time may be an important intervention for those at higher risk of delirium.

Obesity is associated with higher long-term mortality after aortic valve replacement with small prosthesis.

OBJECTIVE: Although many studies have evaluated the impacts of obesity on various medical treatments, it is not known whether obesity is related to late mortality with implantation of small aortic prosthesis. This study evaluated the effect of obesity on late survival of patients after aortic valve replacement (AVR) with implantation of small aortic prosthesis (size ≤ 21 mm). METHODS: From January 1998 to December 2008, 536 patients in our institution who underwent primary AVR (307 patients with smaller prostheses) survived the 30 days after surgery. Patients were categorised as normal weight if body mass index (BMI) was ≤ 25 kg/m(2), as overweight if BMI 25-30 kg/m(2), and as obese if BMI ≥ 30 kg/m(2). Data were collected at the third-month (M), sixth-M, first-year (Y), third-Y, fifth-Y, and eighth-Y after operation. RESULTS: By multivariable analysis, obesity was a significant independent factor of late mortality (hazard ratio [HR]: 1.59; p=0.006). The obese and overweight groups of patients exhibited lower survival (p<0.001) and a higher proportion in NYHA class III/IV (p<0.01) compared with the normal group. Lower EOAI and higher left ventricular mass index were found in the obese and overweight groups, but we saw no significant variance in LVEF among the three groups. CONCLUSIONS: Obesity was associated with increased late mortality of patients after AVR with implantation of small aortic prosthesis. Being obese or and overweight may also affect the NYHA classification, even in the longer term.

Single coronary ostium with obstructive hypertrophic cardiomyopathy treated using the Morrow procedure: a case report.

BACKGROUND: Hypertrophic cardiomyopathy is a commonly inherited heart disease. In addition, single coronary artery (SCA) is a rare congenital anomaly of the coronary arteries. And SCA concomitant with severe hypertrophic obstructive cardiomyopathy (HOCM) has seldom been reported in the literature. However, such cases have not been reported to be treated with the Morrow procedure. CASE PRESENTATION: Herein, we presented a case of a 64-year-old female diagnosed with a single left coronary artery with severe HOCM. The HOCM was treated with the Morrow procedure. The patient was discharged on the seventh postoperative day and was asymptomatic during the follow-up. CONCLUSION: To our knowledge, this is the first study reporting a single left coronary artery with severe HOCM treated with the Morrow procedure. In addition, myocardial protection by cardioplegia antegrade perfusion was safe for the patient with SCA and HOCM.

The first case series analysis on efficacy of esmolol injection for in-hospital cardiac arrest patients with refractory shockable rhythms in China.

Background: This study assessed the effects of esmolol injection in patients with in-hospital cardiac arrest (IHCA) with refractory ventricular fibrillation (VF)/pulseless ventricular tachycardia (pVT). Methods: From January 2018 to December 2021, 29 patients with IHCA with refractory shockable rhythm were retrospectively reviewed. Esmolol was administered after advanced cardiovascular life support (ACLS)-directed procedures, and outcomes were assessed. Results: Among the 29 cases, the rates of sustained return of spontaneous circulation (ROSC), 24-h ROSC, and 72-h ROSC were 79%, 62%, and 59%, respectively. Of those patients, 59% ultimately survived to discharge. Four patients with cardiac insufficiency died. The duration from CA to esmolol infusion was significantly shorter for patients in the survival group (SG) than for patients in the dead group (DG) (12 min, IQR: 8.5-19.5 vs. 23.5 min, IQR: 14.4-27 min; p = 0.013). Of those patients, 76% (22 of 29) started esmolol administration after the second dose of amiodarone. No significant difference was observed in the survival rate between this group and groups administered an esmolol bolus simultaneously or before the second dose of amiodarone (43% vs. 64%, p = 0.403). Of those patients, 31% (9 of 29) were administered an esmolol bolus for defibrillation attempts ≤ 5, while the remaining 69% of patients received an esmolol injection after the fifth defibrillation attempt. No significant differences were observed in the rates of ≥ 24-h ROSC (67% vs. 60%, p = 0.73), ≥ 72-h ROSC (67% vs. 55%, p = 0.56), and survival to hospital discharge (67% vs. 55%, p = 0.56) between the groups administered an esmolol bolus for defibrillation attempts ≤ 5 and defibrillation attempts > 5. Conclusion: IHCA patients with refractory shockable rhythms receiving esmolol bolus exhibited a high chance of sustained ROSC and survival to hospital discharge. Patients with end-stage heart failure tended to have attenuated benefits from beta-blockers. Further large-scale, prospective studies are necessary to determine the effects of esmolol in patients with IHCA with refractory shockable rhythms.

Exosomes derived from human umbilical cord mesenchymal stem cells promote osteogenesis through the AKT signaling pathway in postmenopausal osteoporosis.

Postmenopausal osteoporosis (PMO) is a relatively common disease characterized by low bone mass and microstructural changes of trabecular bone. The reduced bone strength is caused a variety of complications, including fragility fracture and sarcopenia. We used CCK-8 and EdU assays to evaluate cell proliferation rates. The osteogenesis effect was detected using ALP staining, alizarin red staining, and q-PCR. In vivo, the effects of exosomes derived from HUC-MSCs were evaluated using HE staining, IHC staining and Masson staining. In addition, we explored the mechanism of exosomes and found that the AKT signaling pathway played an important role in osteogenesis and cell proliferation. This paper mainly explored the function of exosomes derived from human umbilical cord mesenchymal stem cells (HUC-MSCs) and provided a new strategy for the treatment of postmenopausal osteoporosis. In conclusion, exogenous administration of exosomes can contribute to the treatment postmenopausal osteoporosis to a certain extent.

[Pretreatment of isolated vein with rapamycin nanoparticles inhibits vein graft stenosis in rabbits].

OBJECTIVE: To explore the effects of pretreatment of carbopol-encapsulated rapamycin-loaded nanoparticles (RPM-NP) on vein graft stenosis in a rabbit vein graft model. METHODS: A segment of common carotid artery was replaced with a segment of external jugular vein in 40 rabbits. They were separated into four treatment groups, i.e. Group A: vein grafts were pretreated with intraluminal RPM-NP perfusion; Group B: peripheral venous veins were injected with RPM-NP; Group C: vein grafts received an equivalent perfusion of empty vehicle; Group D: vein grafts received no treatment. At Day 28 post-operation, the grafts and normal veins were harvested for histological examinations to analyze the indicators of intimal thickness, internal diameter, intimal/media thickness ratio and collagen volume index. RESULTS: At Day 28 post-operation, the intimal/media thickness ratios were 0.26 ± 0.02, 0.73 ± 0.05, 0.71 ± 0.04, 0.69 ± 0.03 and 0.24 ± 0.01 in Groups A, B, C and D and the normal vein; the collagen volume index 0.24 ± 0.03, 0.56 ± 0.06, 0.53 ± 0.07, 0.49 ± 0.08 and 0.21 ± 0.01 respectively. Compared with the normal veins, the pathological indicators of vein graft intimal thickness, internal diameter, intimal/media thickness ratio and collagen volume index had significant differences in Groups B, C and D (all P < 0.05). But there were no significant differences among 3 groups (all P > 0.05). Compared with the normal vein, the parameters of vein graft intimal thickness, internal diameter, intimal/media thickness ratio and collagen volume index had no significant difference in Group A (all P > 0.05). But as compared with other groups, these indicators had statistical significant difference in Group A (all P < 0.05). CONCLUSION: The local pretreatment of isolated vein with rapamycin nanoparticles may inhibit neointimal hyperplasia and prevent effectively vein graft stenosis.

Ethyl Pyruvate Alleviates Pulmonary Hypertension through the Suppression of Pulmonary Artery Smooth Muscle Cell Proliferation via the High Mobility Group Protein B1/Receptor for Advanced Glycation End-Products Axis.

PURPOSE: Pulmonary arterial hypertension (PAH) is a formidable disease with no effective treatment at present. With the goal of developing potential therapies, we attempted to determine whether ethyl pyruvate (EP) could alleviate PAH and its mechanism. METHODS: Pulmonary smooth muscle cells were cultured in conventional low-oxygen environments, and cellular proliferation was monitored after treatment with either EP or phosphate-balanced solution (PBS). Expression of high mobility group protein B1 (HMGB1) and receptor for advanced glycation end-products (RAGE) protein were detected by western blot. After hyperkinetic PAH rat models were treated with EP, hemodynamic data were collected. Right ventricular hypertrophy and pulmonary vascular remodeling were evaluated. Expression of HMGB1 and RAGE protein was also detected. RESULTS: In vitro, proliferative activity increased in low-oxygen environments, but was inhibited by EP treatment. Furthermore, Western blotting showed the decreased expression of HMGB1 and RAGE protein after EP treatment. In vivo, pulmonary artery pressures were attenuated with EP. Right ventricular hypertrophy and pulmonary vascular remodeling were also reversed. Additionally, the expression levels of HMGB1 and RAGE were reduced in lung tissues. CONCLUSIONS: EP can alleviate PAH by suppressing the proliferation of pulmonary artery smooth muscle cells via inhibition of HMGB1/RAGE expression.

Liver kinase B1 inhibits smooth muscle calcification via high mobility group box 1.

Vascular calcification is a common pathological feature of atherosclerosis, chronic kidney disease, vascular injury, and aging. Liver kinase B1 (LKB1) plays pivotal roles in cellular processes such as apoptosis, metabolism, and cell cycle regulation. In addition, growing evidence has indicated that LKB1 functions as a tumor suppressor gene. However, its role in vascular calcification has not been reported. LKB1flox/flox mice were hybridized with SM22-CreERT2 transgenic mice and adult mice received tamoxifen to obtain smooth muscle-specific LKB1-knockout (LKB1SMKO) mice. LKB1 expression was decreased under calcifying conditions, and LKB1 overexpression had a protective effect on vascular calcification. However, high mobility group box 1 (HMGB1) overexpression partially counteracted the promotion of vascular calcification induced by LKB1 overexpression. Mechanically, LKB1 could bind to HMGB1 to promote HMGB1 degradation. Furthermore, LKB1SMKO mice showed intensified vascular calcification, which was alleviated by treatment with the HMGB1 inhibitor glycyrrhizic acid. Based on our results, LKB1 may inhibit vascular calcification via inhibiting HMGB1 expression.

Cryogel biocomposite containing chitosan-gelatin/cerium-zinc doped hydroxyapatite for bone tissue engineering.

The present examination includes manufacture and portrayal of cryogel bio-composite implants containing chitosan-gelatin (CS-GT), cerium-zinc doped hydroxyapatite (CS-GT/Ce-Zn-HA) by cryogelation technique. The prepared cryogel biocomposites (CS-GT/HA and CS-GT/Ce-Zn-HA) were described by scanning electron microscope (SEM) and X-Ray diffraction (XRD) contemplates. The expansion of Ce-Zn in the CS-GT implants essentially expanded growing, diminished swelling, expanded protein sorption, and expanded bactericidal movement. The CS-GT/Ce-Zn-HA biocomposite had non-toxic towards rodent osteoblast cells. So the created CS-GT/Ce-Zn-HA biocomposite has favorable and potential applications over the CS-GT/HA platforms for bone tissue engineering.

Employing the Sirolimus-Eluting Poly (Propylene Carbonate) Mesh for the Prevention of Arteriovenous Graft Stenosis in Rats.

Poly (propylene carbonate, PPC) is a new member of the aliphatic polyester family. An outstanding feature of PPC is that it produces mainly water and carbon dioxide when degraded in vivo, causing minimal side effects. This unique property together with excellent biocompatibility and biodegradability makes PPC a promising material for drug delivery. In this study, we explored the effect of the sirolimus (an inhibitor of cell growth)-eluting PPC mesh on graft stenosis and its possible mechanisms in a rat arteriovenous grafting model. The PPC mesh was prepared by electrospinning. A jugular vein to abdominal aortic autograft transplantation model was established in rats. The graft was then treated by wrapping with the drug mesh or the drug-free mesh or left untreated. Four weeks posttransplantation, neointima was measured with hematoxylin and eosin staining, matrix metalloproteinase-2 (MMP-2), and MMP-9, and proliferating cell nuclear antigen (PCNA) in the grafts were assayed by Western blotting and immunohistochemistry, respectively. In vitro rat aortic adventitial fibroblast cell (RAAFC) migration was assessed using the Boyden chamber assay, and phospho-mammalian target of rapamycin (mTOR) levels in RAAFCs were determined by Western blotting. Animals with the drug mesh had an intimal area index of 4.87% ± 0.98%, significantly lower than that of the blank group (14.21% ± 2.56%) or the PPC group (15.03% ± 2.35%, both P < .05). The sirolimus mesh markedly suppressed MMP-2 and MMP-9 expression, decreased PCNA-positive cell numbers, inhibited RAAFC migration, and reduced phospho-mTOR levels. Our data suggest that the sirolimus-eluting PPC mesh might be potentially applied for the management of grafting stenosis.