Endovascular repair of thoracic aortic disease with isolated left vertebral artery and unfavorable proximal landing zone using fenestrated castor stent-graft.

Objective: The main purpose of this study was to evaluate the safety and efficacy of Castor single-branched stent-graft combined with fenestrated technique in treatment of thoracic aortic disease (TAD) with unfavorable proximal landing area (PLZ) and isolated left vertebral artery (ILVA). Methods: From January 2018 to March 2022, 8 patients with TAD (6 patients with type B aortic dissections, 1 patient with type B intramural hematomas, and 1 patient with thoracic aortic aneurysm) underwent thoracic endovascular aortic repair with fenestrated Castor stent-graft due to the existence of ILVA and unfavorable PLZ. Demographic characteristics, surgical details, postoperative complications, follow-up and postoperative CTA imaging results were collected and analyzed. Results: The primary technical success rate was 100%. The mean operation time was 115 min (range, 70-180 min). All the left subclavian arteries (LSAs) and ILVAs of the eight patients were revascularized by fenestrated Castor stent-grafts. During the follow-up period, no deaths and complications were observed. No internal leakage, aortic rupture, retrograde type A dissection were found on computed tomography angiography. All of the LSAs and ILVAs maintained patency without stenosis. Conclusion: Castor single-branched stent-graft implantation combined with fenestration technique may be safe and feasible for TAD patients with ILVA and unfavorable PLZ.

Short-term follow-up of proximal aorta remodeling after zone 2 thoracic endovascular aortic repair for acute type B aortic dissection.

BACKGROUND: To evaluate the early remodeling of the proximal aorta in patients with acute type B aortic dissection (ATBAD) after zone 2 thoracic endovascular aortic repair (TEVAR). METHODS: From January 2016 to May 2022, 53 ATBAD patients underwent zone 2 TEVAR were divided into two groups, the Castor single-branched stent-graft (CSS) group (n = 26) and the common stent-graft group (n = 27). Three-dimensional imaging created by computed tomography angiography was used to measure different parameters of the aorta, such as angulation, cross-sectional area (CSA), length and tortuosity. Early remodeling of the proximal aorta was evaluated by comparing geometric parameters of the proximal aorta before and 3 months after surgery. RESULTS: In terms of angle, the postoperative angle of aortic arch to ascending aorta, descending aorta increased in all patients compared with that before surgery (all P < 0.05), while the angle of aortic arch to left subclavian artery increased after surgery only in the CSS group (P < 0.001); As for CSA, the CSA of distal aortic arch and true lumen increased (all P < 0.05), while the CSA of false lumen decreased in both groups after operation (all P < 0.05); Only in CSS group, the CSA of the ascending aorta, proximal aortic arch and total descending thoracic aorta decreased after surgery (all P < 0.05); In terms of length, the aortic arch prolonged after operation in both groups (P = 0.018 and P = 0.004, respectively). In addition, the ascending aorta tortuosity decreased in the CSS group after surgery (P = 0.011). There was no significant difference in the alterations of other aortic parameters after operation (P > 0.05). CONCLUSIONS: The CSS implantation provided a more relatively safe and effective treatment for acute type B aortic dissection patients with unfavorable proximal landing zone. It can promote the earlier remodeling of the proximal aorta compared with the common stent-graft implantation after zone 2 TEVAR.

A rare case on anomalous pulmonary venous drainage in congenital cardiovascular disease.

Anomalous pulmonary veins drain into the right side of the left atrium is an uncommon variety of anomalous pulmonary venous return. Rarely, anomalous pulmonary venous drainage combined with cor triatriatum and atrial septal defect. We presented the imaging findings of a male patient who had anomalous pulmonary venous drainage which has not previously been described.

Comparison of two techniques in proximal anastomosis in acute type A aortic dissection.

Background: The proximal anastomosis is an important procedure during the acute type A aortic dissection (AAAD) surgery. The conventional method is a double patch sandwich technique with Teflon felt. Adventitial eversion and prosthesis eversion technique as a novel approach has been applied to many patients in our center. Herein, This technique would be introduced, and the perioperative and 1-year follow-up results of the two different anastomosis methods were also evaluated. Methods: Between December 2017 and May 2021, 143 AAAD patients who underwent total arch replacement (TAR) and frozen elephant trunk (FET) implantation were included in this retrospective study. Patients were divided into the eversion technique group (adventitial eversion and prosthesis eversion technique for proximal anastomosis, n = 64) and the sandwich technique group (n = 79). Results: The medical records were analyzed and compared between the groups. The mean operation time was 466 ± 73 min in the eversion technique group and 513 ± 81 min in the sandwich technique group (P < 0.001). Compared with the sandwich technique group, the eversion technique group also showed a shorter time on proximal anastomosis (38 ± 12 min vs. 58 ± 20 min, P < 0.001), cardiopulmonary bypass (195 ± 26 vs. 211 ± 40 min, P = 0.003), and aortic cross-clamp (120 ± 23 min vs. 134 ± 27 min, P = 0.002). Furthermore, a decreased proportion of >600 ml fresh frozen plasmas transfusion was observed in eversion technique group (10.9% vs. 34.2%, P = 0.002). No statistical differences were found in the postoperative morbidities and 1-year follow-up outcomes. Conclusion: Proximal anastomosis with adventitial eversion and prosthesis eversion technique is a promising surgical option for AAAD patients, with favorable perioperative and 1-year follow-up results.

Silencing TUFM Inhibits Development of Monocrotaline-Induced Pulmonary Hypertension by Regulating Mitochondrial Autophagy via AMPK/mTOR Signal Pathway.

Pulmonary arterial hypertension (PAH) is an extremely malignant cardiovascular disease which mainly involves the uncontrollable proliferation of the pulmonary arterial smooth muscular cells (PASMCs). Recent studies have confirmed that mitochondria play an important role in the pathogenesis of pulmonary hypertension through sensing cell hypoxia, energy metabolism conversion, and apoptosis. As a mitochondrial membrane protein, TUFM has been regarded to be related to mitochondrial autophagy (mitophagy), apoptosis, and oxidative stress. Considering these factors are closely associated with the pathogenesis of PAH, we hypothesize that TUFM might play a role in the development of PAH. Our preliminary examination has showed TUFM mainly expressed in the PASMCs, and the subsequent test indicated an increased TUFM expression in the SMCs of pulmonary arteriole in monocrotaline- (MCT-) induced PAH rat model compared with the normal rat. The TUFM knockdown (Sh-TUFM) or overexpressed (OE-TUFM) rats were used to establish PAH by treating with MCT. A notable lower pulmonary arterial systolic pressure together with slightly morphological changes of pulmonary arteriole was observed in the Sh-TUFM group compared with the single MCT-induced PAH group. Increased levels of P62 and Bax and reduced LC3II/I, BECN1, and Bcl2 were detected in the Sh-TUFM group, while the expressions of these proteins in the OE-TUFM group were contrast to the results of the Sh-TUFM group. To elucidate the possible mechanism underlying biological effect of TUFM in PAH, PASMCs were treated with silence or overexpression of TUFM and then exposed to hypoxia condition. An obviously high levels of P62 and Bax along with a decreased LC3 II/I, BECN1, ULK1, Atg12, Atg13, and Bcl2 levels were noticed in cells with silence of TUFM. Moreover, the phosphorylated AMPK and mTOR which was well known in mitophagy modulating vary by the alternation of TUFM. These observations suggested that TUFM silence inhibits the development of MCT-induced PAH via AMPK/mTOR pathway.

Endovascular Aortic Repair With Castor Single-Branched Stent-Graft in Treatment of Acute Type B Aortic Syndrome and Aberrant Right Subclavian Artery.

OBJECTIVE: In this retrospective study, we presented the results of Castor single-branched stent-graft in a small series of patients with acute type B aortic syndrome and aberrant right subclavian artery (ARSA). METHODS: Between January 2019 and November 2019, 5 patients were diagnosed with acute type B aortic syndrome and ARSA (4 patients with intramural hematoma and ARSA, 1 patient with type B aortic dissection and ARSA). All the patients underwent thoracic endovascular aortic repair (TEVAR) using Castor single-branched stent-graft. In-hospital and 3-month outcomes were collected. RESULTS: The mean operative time was 116 ± 20.43 minutes (range 90-145). All the TEVAR procedures were successfully performed without conversion to open surgery (100% success rate). All the ARSAs of the 5 patients were revascularized in situ by Castor single-branched stent-grafts. No deaths and complications were observed in the 3-month follow-up. The maximal diameters of diseased aortas in the 4 patients with IMH decreased 3 months after TEVAR. The false lumen in the graft-covered segment was completely thrombosed in the patient with type B aortic dissection. CONCLUSIONS: Castor single-branched stent-graft may be a good choice in treatment of acute type B aortic syndrome and aberrant right subclavian artery.

Early Outcomes of Left Subclavian Artery Revascularization Using Castor Single-Branched Stent-Graft in the Treatment of Type B Aortic Dissection or Intramural Hematoma.

BACKGROUND: More evidence was required to guide the management of left subclavian artery (LSA) during thoracic endovascular aortic repair (TEVAR). The present study aimed to compare the outcomes of LSA coverage with LSA revascularization. Another purpose of this study was to share our experience of LSA revascularization with castor single-branched stent-graft. METHODS: From January 2016 to December 2019, 134 patients with type B aortic dissection (TBAD) or intramural hematoma (IMH) were enrolled and divided into two groups, the LSA-covered group (n = 61) and the LSA-revascularized group (with castor single-branched stent-graft, n = 73). The results, such as in-hospital and 30-day mortality, stroke, paraplegia, left arm ischemia, operation time, endoleak, were compared between the two groups. RESULTS: The incidence of 30-day stroke in the LSA-covered group (8.2%) was significantly higher compared with the LSA-revascularized group (0%, P = 0.018). 30-day ischemia of left arm occurred in more patients in the LSA-covered group (11.5%, P = 0.003). No statistical difference was found in the incidences of paraplegia, endoleak, in-hospital mortality, and 30-day mortality. CONCLUSIONS: LSA should be revascularized during TEVAR to reduce the incidences of stroke and left arm ischemia. Castor single-branched stent-graft was feasible and safe for treating TBAD or IMH.

Effect of different types of cerebral perfusion for acute type A aortic dissection undergoing aortic arch procedure, unilateral versus bilateral.

BACKGROUND: Antegrade cerebral perfusion (ACP), including unilateral and bilateral, is most commonly used for cerebral protection in aortic surgery. There is still no consensus on the superiority of the two methods. Our research aimed to investigate the clinical effects of u-ACP and b-ACP. METHODS: 321 of 356 patients with type A aortic dissection were studied retrospectively. 124 patients (38.6%) received u-ACP, and 197 patients (61.4%) received b-ACP. We compared the incidence of postoperative neurological complications and other collected data between two groups. Besides, we also analyzed perioperative variables to find the potential associated factors for neurological dysfunction (ND). RESULTS: For u-ACP group, 54 patients (43.5%) had postoperative neurological complications, including 22 patients (17.7%) with permanent neurologic dysfunction (PND) and 32 patients (25.8%) with temporary neurologic dysfunction (TND). For b-ACP group, 47 patients (23.8%) experienced postoperative neurological complications, including 16 patients (8.1%) of PND and 31 patients (15.7%) of TND. The incidence of PND and TND were significantly different between two groups along with shorter CPB time (p = 0.016), higher nasopharyngeal temperature (p≦0.000), shorter ventilation time (p = 0.018), and lower incidence of hypoxia (p = 0.022). Furthermore, multivariate stepwise logistic regression analysis confirmed that preoperative neurological dysfunction (OR = 1.20, p = 0.028), CPB duration (OR = 3.21, p = 0.002), and type of cerebral perfusion (OR = 1.48, p = 0.017) were strongly associated with postoperative ND. CONCLUSIONS: In our study, it was observed that b-ACP procedure exhibited shorter CPB time, milder hypothermia, shorter ventilation time, lower incidence of postoperative hypoxia, and neurological dysfunction compared to u-ACP. Meanwhile, the incidence of ND was independently associated with three factors: preoperative neurological dysfunction, CPB time, and type of cerebral perfusion.

Oxygenation impairment after total arch replacement with a stented elephant trunk for type-A dissection.

OBJECTIVE: To study the risk factors of oxygenation impairment in patients with type-A acute aortic dissection who underwent total arch replacement with a stented elephant trunk. METHODS: In this study, 169 consecutive patients were enrolled who were diagnosed with type-A acute aortic dissection and underwent a total arch replacement procedure at the Qilu Hospital of Shandong University between January 2015 and February 2017. Postoperative oxygenation impairment was defined as arterial oxygen partial pressure/inspired oxygen fraction ≤ 200 with positive end expiratory pressure ≥ 5 cm H2O that occurred within 72 hours of surgery. Perioperative clinical characteristics of all patients were collected and univariable analyses were performed. Risk factors associated with oxygenation impairment identified by univariable analyses were included in the multivariable regression analysis. RESULTS: The incidence of postoperative oxygenation impairment was 48.5%. Postoperative oxygenation impairment was associated with prolonged mechanical ventilation time, intensive care unit stay, and hospital stay. Multivariable regression analysis demonstrated that body mass index (odds ratio [OR], 1.204; 95% confidence interval [CI], 1.065-1.361; P = .003), preoperative oxygenation impairment (OR, 9.768; 95% CI, 4.159-22.941; P < .001), preoperative homocysteine (OR, 1.080; 95% CI, 1.006-1.158; P = .032), circulatory arrest time (OR, 1.123; 95% CI, 1.044-1.207; P = .002), and plasma transfusion (OR, 1.002; 95% CI, 1.001-1.003; P = .002) were significantly associated with postoperative oxygenation impairment. CONCLUSIONS: Postoperative oxygenation impairment is a common complication of surgery for type-A acute aortic dissection. Body mass index, preoperative oxygenation impairment, preoperative homocysteine, circulatory arrest time, and plasma transfusion were independent risk factors for oxygenation impairment after a total arch replacement procedure.

Applicability of electrospun polypropylene carbonate polymers as a drug carrier for sirolimus.

Polypropylene carbonate (PPC), a biodegradable aliphatic polyester, exhibits one particular advantage over other polyesters, which is that following degradation in vivo, it primarily produces H2O and CO2, causing minimal side effects. Although PPC exhibits limited mechanical strength, and is therefore not able to serve as a scaffold to support tissue regeneration, it may be suitable for drug delivery; however, this requires further investigation. In the present study, electrospinning was applied to generate PPC polymers containing sirolimus, a cell growth­inhibiting drug which is used to treat restenosis. The properties of PPC­sirolimus polymers were examined using scanning electron microscopy, differential scanning calorimetry and in vitro degradation assays. Drug loading and entrapment efficiency were determined, and in vitro sirolimus­release from the polymer was assessed. Furthermore, the effect of PPC­sirolimus polymers on cell growth was measured using an MTT assay in vitro. The results of the present study demonstrated that electrospun PPC polymers formed a uniform three­dimensional, grid­intertwined, net­like structure; the surface of the polymers was smooth and the diameter was ~3 µm. Differential scanning calorimetry analysis demonstrated that sirolimus existed in an amorphous state in the polymer. Following soaking in PBS for 4 weeks, the polymer swelled and the net­like structure broke down and fragmented. Sirolimus loading and entrapment efficiency were 10.3±3.2 and 95.1±10.6%, respectively. Sirolimus­release from PPC­sirolimus polymers continued for 28 days in PBS. PPC­sirolimus markedly inhibited the growth of rat aortic adventitial fibroblast cells, an effect which was not observed with PPC alone. The results of the present study suggest that PPC polymers are a promising alternative drug carrier for sirolimus.

Hypoxia-inducible factor 1a induces phenotype switch of human aortic vascular smooth muscle cell through PI3K/AKT/AEG-1 signaling.

To date, hypoxia-inducible factor 1a (HIF-1a) and astrocyte elevated gene-1 (AEG-1) have been involved in the proliferation, migration and morphological changes of vascular smooth muscle cells. However, the potential relationship of HIF-1a-AEG-1 pathway in human aortic smooth muscle cell (HASMC) has not been reported. In the present study, in-vitro assays were utilized to explore the potential impact of HIF-1a-AEG-1 signaling on HASMC phenotype. Here, we found that HIF-1a expression was up-regulated in the media of thoracic aortic dissection tissues as compared with normal aortic tissues, and was associated with increased apoptotic SMCs and decreased AEG-1 expression. Mechanically, hypoxia promoted the expression of HIF-1a by PI3K-AKT pathway in HASMCs; HIF-1a further suppressed the expressions of AEG-1, a-SMA and SM22a, and promoted osteopontin (OPN) expression. Functionally, HIF-1a inhibited the proliferation and migration of HASMCs. However, si-HIF-1a or Akt inhibitor abrogated HIF-1a-mediated related expressions and biological effects above. In conclusion, HIF-1a induces HASMC phenotype switch, and closely related to PI3K/AKT and AEG-1 signaling, which may provide new avenues for the prevention and treatment of aortic dissection diseases.

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.

Effects of Ulinastatin on Perioperative Inflammatory Response and Pulmonary Function in Cardiopulmonary Bypass Patients.

The aim of this study was to investigate whether ulinastatin (UTL) has protective effects on perioperative proinflammatory cytokines and lung injury in cardiopulmonary bypass (CPB) patients. The study included 60 patients undergoing CPB who were randomly divided into a UTL group and a control group. Blood routine examination and inflammatory cytokines concentrations were detected after anesthetic induction (T1), immediately after aortic valve opening (T2), and 4 (T3) and 24 (T4) hours after weaning from CPB. Flow cytometry was used to detect TLR4 and HSP70 expressions. Arterial blood gas and respiratory function were analyzed at the same time points. Compared with the control group, the levels of IL-2, IL-8, TNF-α, NE, TLR4, PA - aDO2, and RI at T2 were significantly lower, whereas HSP70, PaO2, OI, Cd, and Cs were higher in the UTL group (all P < 0.05). Relative to the control group at T3, white blood cell count, TLR4, IL-2, IL-6, IL-8, TNF-α, NE, and RI decreased significantly, whereas IL-10, HSP70, PaO2, OI, and Cs increased in the UTL group (all P < 0.05). At T4, IL-2, IL-6, IL-8, TNF-α, TLR4, and PaCO2 in the UTL group were significantly lower, and PaO2, IL-10, HSP70, and Cs were higher than in the control group (all P < 0.05). Our data show strong evidence that UTL suppresses proinflammatory cytokine elevation and upregulates release of anti-inflammatory mediators, reducing pulmonary injury and improving pulmonary function after CPB.

A single-center experience of hemofiltration treatment for acute aortic dissection (Stanford type A) complicated with postoperative acute renal failure.

OBJECTIVE: To investigate the effect of continuous venovenous hemofiltration (CVVH) for aortic dissection patients with acute renal failure after surgery in retrospective manner. METHODS: A total of thirty-seven aortic dissection patients with postoperative acute renal failure accepted CVVH therapy. The effect of CVVH was evaluated by analyzing clinical condition changes and laboratory examination results. RESULTS: After treatment of CVVH, renal function and clinical symptoms were significantly improved in thirty patients. Eight of the thirty patients got completely renal function recovery within two weeks after CVVH therapy; and twenty-two of the thirty patients got completely renal function recovery within four weeks after CVVH therapy. Nevertheless, seven patients got no benefit from CVVH therapy with poor prognosis. CONCLUSION: CVVH is an effective treatment to most aortic dissection patients with postoperative acute renal failure. The effect of CVVH was correlated with original renal function, early CVVH therapy, and continuous intensive care.

Astrocyte elevated gene-1 regulates CCL3/CCR5-induced epithelial-to-mesenchymal transition via Erk1/2 and Akt signaling in cardiac myxoma.

In recent years, astrocyte elevated gene-1 (AEG-1) has been reported as a key mediator that is involved in the epithelial-to-mesenchymal transition (EMT) process. However, the mechanisms underlying CCL3/CCR5-AEG-1 pathway-mediated EMT in cardiac myxoma (CM) has not been well featured till now. We used immnohistochemistry and immunoblotting to assess the expression of CCR5 and AEG-1 in 30 cases of CM tissues and cells. Subsequently, cultured CM cells were treated with si-AEG-1 or si-CCR5 and then subjected to in vitro assays. We observed that CCR5 and AEG-1 proteins were highly expressed in CM tissues (73.3 and 76.7%, respectively) and closely correlated with tumor size (>5 cm). Importantly, we validated the expression of AEG-1, p-Erk1/2, p-Akt, vimentin, N-cadherin and MMP2 increased in the CM cell with CCL3 treatment in a time- and concentration-dependent manner. When CM cells were treated with si-CCR5, the expression of AEG-1, p-Erk1/2, p-Akt, vimentin, N-cadherin and MMP2 was downregulated. In addition, when CM cells were treated with si-AEG-1, the expression of p-Erk1/2, p-Akt, vimentin, N-cadherin and MMP2 was also downregulated. Using the cell cycle and proliferation assay, the knockdown of AEG-1 inhibited the entry of G1 into S phase and the proliferation capacity of CM cells. In conclusion, AEG-1 mediates CCL3/CCR5-induced EMT development via both Erk1/2 and Akt signaling pathway in CM patients, which indicates CCL3/CCR5-AEG-1-EMT pathway could be suggested as a useful target to affect the progression of CM.

Astrocyte-elevated gene-1 mediates insulin-like growth factor 1-induced the progression of cardiac myxoma.

Recently, astrocyte-elevated gene-1 (AEG-1) and insulin-like growth factor 1 (IGF-1) have been involved in the regulation of multiple signaling pathways in tumorigenesis. To date, the detailed mechanisms underlying IGF-1-AEG-1 pathway-induced proliferation and apoptosis in cardiac myxoma (CM) was not reported. In the present study, we used immnohistochemistry, immunoblotting, and qRT-PCR to detect the expression profile of IGF-1 and AEG-1 in 90 CM tissues, and then cultured CM cells were subjected to si-AEG-1, in vitro, and in vivo assays. Our findings showed that IGF-1 and AEG-1 were obviously upregulated in CM tissues and markedly associated with tumor size. When CM cells were treated with si-AEG-1, si-AEG-1 attenuated IGF-1-induced CM cell growth and enhanced cell apoptosis. Mechanically, we validated the expression of AEG-1, p-Erk1/2, and p-Akt increased in CM cells in response to IGF-1 treatment in a time-dependent manner. However, si-AEG-1 affected the expression of these proteins. Functionally, we found the knockdown of AEG-1-inhibited G1/S transition and tumor formation of CM cells. In conclusion, AEG-1 regulates IGF-1-induced proliferation and apoptosis via Erk1/2 and Akt signaling in CM development, which suggests IGF-1-AEG-1 signaling could be recommended to be a useful target to exert anti-tumor effects on CM.

Establishment and comparison of two reliable hyperkinetic pulmonary hypertension models in rabbits.

OBJECTIVES: We sought to explore and create a reliable, convenient, and economic hyperkinetic pulmonary artery hypertension (PAH) model and confirm the exact time of establishing a reversible or irreversible model to serve as a platform for future studies. METHODS: We used a common carotid artery and jugular vein shunt with an anastomosis and cuff to create a hyperkinetic PAH model in rabbits. At 1, 2, 3, 6, and 12 months postoperatively, the systolic pressure, mean pulmonary arterial pressure, and mean arterial pressure were measured by catheterization and the right ventricle hypertrophy index was calculated. Pathologic changes in the small pulmonary arteries were observed with hematoxylin and eosin staining, and the Heath-Edwards classification system was used to evaluate PAH. RESULTS: The anastomosis and cuff graft groups both increased in systolic pressure, mean pulmonary arterial pressure (P<.05), and right ventricle hypertrophy index (P<.05). However, the anastomosis method resulted in a lower mortality rate, greater patency, and overall success rate compared with the cuff graft method (P<.05). Furthermore, from the observed pathologic changes and the Heath-Edwards classification system, a reversible and an irreversible PAH model was established at 3 and 6 months postoperatively, respectively. CONCLUSIONS: The common carotid artery and jugular vein anastomosis method is a stable hyperkinetic PAH model in rabbits. Reversible and irreversible PAH models were established at 3 and 6 months postoperatively, respectively.

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.

An important role of matrix metalloproteinase-8 in angiogenesis in vitro and in vivo.

AIMS: Growing evidence suggests a close association of plaque angiogenesis with atherosclerotic plaque formation and progression, and an important role of matrix metalloproteinase (MMP) in angiogenesis and atherosclerosis. We attempted to investigate the functional involvements of MMP8 in angiogenesis. METHODS AND RESULTS: Knockdown of MMP8 in human umbilical vein endothelial cells (HuVECs) with MMP-8 shRNA lentivirus resulted in a decrease in in vitro capillary-like network formation, cell proliferation and migration, and impaired its capacity of in vivo angiogenesis. Less nuclear accumulation of ß-catenin and lower ß-catenin target gene expression levels was observed in the HuVECs expressing lower levels of endogenous MMP8. Knockdown of endogenous MMP8 in HuVECs down-regulated platelet/endothelial cell adhesion molecule-1 (PECAM-1) expression by converting less angiotensin I to II, which is an inducer for PECAM-1 gene expression. Aortic rings isolated from MMP8(-/-)/apoE(-/-) mice had less endothelial cell sprouting, and endothelial cells in MMP8(-/-)/apoE(-/-) mice had a lower ability to migrate into Matrigel plugs and less capacity of proliferation and angiogenesis. Moreover, immunohistochemical analyses revealed that MMP8 was expressed in microvessels within human atherosclerotic plaques and aneurysm. Finally, analyses of MMP8(-/-)/apoE(-/-) and MMP8(+/+)/apoE(-/-) mice fed a Western diet for 12 weeks showed that MMP8-deficient mice had small lesion size and less endothelial cells within atherosclerotic lesions. CONCLUSION: We demonstrated for the first time that MMP8 plays an important role in angiogenesis in vitro and in vivo. Our findings provide new insights into the molecular mechanisms of plaque angiogenesis and suggest that MMP8 is a potential therapeutic target of cardiovascular diseases.