Junhao Jiang

Association of smooth muscle cell phenotypes with extracellular matrix disorders in thoracic aortic dissection

OBJECTIVE Extracellular matrix dysregulation in the aortic media has been considered as the intrinsic factor for the formation of thoracic aortic dissection. However, the mechanisms of extracellular matrix disorders in the dissected aortic media remain unclear. This study was designed to investigate the relevance between smooth muscle cell phenotypes and extracellular matrix disorders in the dissected media. Their interaction may account for the pathogenesis of thoracic aortic dissection. METHODS AND RESULTS Thoracic aortic samples were collected from 10 patients with thoracic aortic dissection and 10 controls. Primary cultures of aortic medial smooth muscle cells were obtained with optimized explant technique. In this study, α-smooth muscle actin, smooth muscle myosin heavy chain 2, and smoothelin were applied as the contractile phenotypic markers and osteopontin was applied as the synthetic marker. Compared with controls, immunostaining and immunoblotting demonstrated that in vivo expression of α-smooth muscle actin, smooth muscle myosin heavy chain 2, and smoothelin were significantly decreased in the dissected media, whereas that of osteopontin was elevated (P<.01 for all). In vitro expression of the phenotypic markers showed the similar patterns. Furthermore, smooth muscle cells derived from the dissected media exhibited enhanced proliferation (P<.01), increased collagens I and III synthesis (2.6- and 4.4-fold, respectively; P<.01 for both), and elevated matrix metalloproteinase-2 production (4.2-fold; P<.01). Consistently, the protein levels of type I and III collagens and matrix metalloproteinase-2 in the dissected media were raised by 4.6-, 4.0-, and 3.7-fold, respectively (P<.01 for all). Collagen deposition was correspondingly increased and elastic fibers were decreased and disrupted. CONCLUSIONS Smooth muscle cells in the dissected media exhibit phenotypic switching from the contractile to the synthetic type. The synthetic smooth muscle cells increase collagen synthesis and matrix metalloproteinase-2 production, both of which can promote collagen deposition and elastin degradation in thoracic aortic dissection.

Endovascular Stent-Graft Repair of Mycotic Aneurysms of the Aorta: A Case Series with a 22-Month Follow-Up

BackgroundThe purpose of the present study was to present a single-institution series of patients with mycotic aneurysms of the aorta treated with endovascular stent-graft technology, and to report the efficacy and short-term durability of this repair.MethodsA retrospective review of seven consecutive patients with mycotic aneurysms of the aorta treated with stent-graft between May 2006 and July 2007. Patients were diagnosed based on typical appearance of imaging together with a positive bacteriology culture or clinical evidence of infection. A bifurcated, aorto-uni-iliac (AUI) stent-graft and cuff were used in the endovascular repair after infection control. The follow-up protocol included regular clinical examination, hematologic tests, and computed tomography scans at 3, 6, 12, and 24 months.ResultsEndovascular aneurysm repair (EVAR) was performed successfully in the seven patients (all men, median age 56 years), with complete exclusion of the aneurysms. Five of the patients had infrarenal aortic aneurysms, and the other two had descending thoracic aortic aneurysms. The median hospital stay was 22 days, with no hospital deaths. No paraplegia or other major complications occurred. The patients remained well, with no evidence of graft infection at a mean follow-up of 22.7 months (range: 17–26 months). A significant reduction in the diameter of the aneurysm sac was noted on computed tomography scans in all the patients at 1 year (mean: 6.5 mm; range: 3–40 mm).ConclusionsEndovascular stent-graft treatment represents an alternative treatment with acceptable short-term outcomes for patients with mycotic aneurysms of the aorta.

The rhythmic expression of clock genes attenuated in human plaque-derived vascular smooth muscle cells

BackgroundAcute myocardial infarction and stroke are more likely to occur in the early morning. Circadian pacemakers are considered to be involved in the process. Many peripheral tissues and cells also contain clock systems. In this study, we examined whether the primary cultured human plaque-derived vascular smooth muscle cells (VSMCs) process circadian rhythmicity; furthermore, we investigated the expression difference of clock genes between normal human carotid VSMCs and human plaque-derived VSMCs.MethodsFifty-six human carotid plaques provided the atherosclerotic tissue, and 21 samples yielded viable cultured primary VSMCs. The normal carotid VSMCs were cultured from donors’ normal carotids. The mRNA levels of the target genes were measured by Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR).ResultsAfter serum shock, both types of cells showed clear circadian expressions of Bmal1, Cry1, Cry2, Per1, Per2, Per3 and Rev-erbα mRNA; meanwhile the Clock mRNA show a rhythmic expression in plaque-derived SMCs but not in normal carotid VSMCs. The expression levels of these main clock genes were significantly attenuated in human plaque-derived VSMCs compared with normal human carotid VSMCs. The rhythm of Bmal1 mRNA in plaque-derived VSMCs was changed.ConclusionThe present results demonstrate that the human plaque-derived VSMCs possess different circadian rhythmicity from that of normal carotid VSMCs. The rhythm changes of clock genes in plaque-derived VSMCs may be involved in the process of atherosclerosis and finally promote the rupture of plaque.

Predictors and treatments of Proglide-related complications in percutaneous endovascular aortic repair.

Purpose To investigate the predictors and treatment of the 6-Fr Perclose Proglide-related complications (PRC) in percutaneous endovascular aortic repair (pEVAR). Methods We retrospectively analyzed the PRC after pEVAR for the treatment of aortic aneurysm or dissection in our center from December 2012 to November 2013. Procedure success was defined as effective functioning of the two devices and local hemostasis. Access-related adverse events included vascular complications and device failures. Operative data and angiographic and computed tomography images were collected to assess the complications and treatment strategy. Results A total of 198 patients with 275 puncture sites underwent pEVAR with the 6-Fr Perclose Proglide. The procedure was successful in 178 patients (89.9%), whereas PRC occurred in 20 cases (10.1%), including 10 device failures and 10 vascular complications. An extra manual ancillary compression was conducted in 7 patients, one more device was used in 8 patients, and surgical repair of the femoral artery was performed in 5 patients. PRC had a tendency to occur in patients with body mass index (BMI)>30 kg/m2 (p = 0.021), thoracic stent grafts (p = 0.038), common femoral artery (CFA) calcification (p = 0.001), CFA depth>4 cm (p = 0.001), and sheath size>20Fr (p = 0.005). Device failure-related mortality was zero. None of the access sites had complications during the midterm follow-up. Conclusions The pre-close technique with 6-Fr Perclose Proglide devices for pEVAR appears to be safe and effective with low technical failure and complication rates. Careful patient selection and proficiency in device manipulation might reduce the device related complications.

Endovascular therapy for stanford type B aortic dissection in 102 cases.

OBJECTIVE To share our experience of 102 cases of endovascular therapy for Stanford type B aortic dissection. METHODS Multiple imaging diagnostic modalities were used preoperatively to obtain the anatomical parameters of the aortic dissection. Stent grafts were implanted using digital subtraction angiography and intravascular ultrasound guidance. Follow-up computed tomography angiography 1 week and 1 year postoperatively was used to evaluate treatment efficacy and reveal complications such as endoleak, migration and fracture of the stent graft. RESULTS Clinical success was achieved in 101 cases (99.0%); one patient (1.0%) died within the perioperative period. Neither postoperative paraplegia nor conversion occurred. Endoleak occurred in 18 cases (17.6%). CONCLUSION Endovascular therapy for Stanford type B aortic dissection is less invasive and leads to less severe complications and shorter hospital stay compared with traditional surgery. The short- and mid-term efficacy are persuasive, but further follow-up is required to determine long-term efficacy.

Strategies for endovascular treatment of complicated splenic artery aneurysms

Objective Endovascular treatment (ET) is being increasingly used for splenic artery aneurysms (SAAs), but systematic treatment strategies have not been defined. We set out to investigate the optimal strategies for ET of complicated SAAs (CSAAs). Methods CSAAs were classified into three types: type I, rupture or impending rupture; type II, at the origin of the splenic artery; and type III, having an aberrant splenic artery from the splenomesenteric trunk (type IIIA) or celiacomesenteric trunk (type IIIB). SAAs treated at our center during the last decade were reviewed, and CSAAs were selected for analysis. Patients’ demographics, clinical manifestations, aneurysm characteristics, ET strategies, and outcomes were analyzed. Results A total of 154 SAAs were identified, with 24 (15.6%) being CSAAs. Open surgery was employed in two patients, whereas 22 patients underwent ET. There were 3 patients with type I (type IIIA co‐occurred in one of them), 5 with type II, and 15 with type III CSAAs. Treatment strategies included the following: immediate and thorough exclusion with embolization of the collaterals for type I; and dense embolization of the sac and outflow artery, with or without embolization of the inflow artery, or covered stent placement in the splenomesenteric trunk or celiacomesenteric, for types II and III. Technical success was achieved in 21 patients (95.5%). Mean follow‐up was 33.7 ± 31.2 months (range, 1.5‐117.0 months). The aneurysms remained completely thrombosed and unenlarged in 21 patients (95.5%). Reintervention was needed in one patient (4.5%) for persistent sac enlargement. The covered stent was asymptomatically occluded in one patient (11.1%). No hepatic or intestinal ischemia or death developed perioperatively or during the follow‐up period. Conclusions With reasonable strategies toward the urgency and thoroughness needed for aneurysm exclusion as well as the anatomic challenges, ET appeared to be feasible, safe, and effective in the management of CSAAs. Graphical abstract Figure. No caption available.

Outcomes and aortic remodelling after proximal thoracic endovascular aortic repair of post type B aortic dissection thoracic aneurysm.

BACKGROUND The objective was to explore the outcomes and aortic remodelling after proximal thoracic endovascular aortic repair (TEVAR) in post type B aortic dissection thoracic aneurysm with a maximal diameter ≥ 5.5cm. PATIENTS AND METHODS 34 cases of type B aortic dissection thoracic aneurysm undergoing proximal TEVAR (coverage of the primary entry and the aneurysm extent) from 2008 to 2013 were retrospectively reviewed with follow-up for at least 2 years. The primary endpoints were 30-day mortality and survival at 2 years. The secondary endpoints were major complication and re-intervention. The aortic remodelling was investigated by comparison of the maximum diameter of the aneurysm and the diameter of true and false lumen at the same level between baseline and 2 years after TEVAR. Besides, we also analysed the possible relevant factors of aortic remodelling including the course of dissection, the involvement of dissection, and the length and shape of the stent graft. RESULTS The 30 day mortality was 2.9 % (1/34). The paraplegia rate post-TEVAR was 2.9 % (1/34). Overall, 32 out of the 34 cases were followed-up for 24 - 79 months. At 2 years, the overall and aortic specific survival were 87.5 % and 90.3 % respectively. The two year freedom from re-intervention rate was 87.5 %. Compared to the preoperative data, maximum diameter of descending aorta at 2 years demonstrated a slight increase (65.4±14.1mm Vs 63.9±9.1mm), but without significance (P>0.05). Meanwhile, we noticed a significant increase of true lumen (P < 0.01) and decrease of false lumen (P < 0.01) at the same level. Relevant analysis showed that positive aortic remodelling of the maximum diameter was associated with chronic phase (≥ 90 days of dissection onset) (P < 0.05) and the application of 150 - 170mm stent grafts (P < 0.05). CONCLUSIONS Proximal TEVAR of post type B dissection thoracic aneurysm had generally favourable short- and mid-term outcomes with low paraplegia rate. Besides, it can achieve a certain extent of aortic remodelling.

Severe compression of a bailout self-expanding chimney stent for rescuing the miscoverage of left common carotid artery during TEVAR of a type B aortic dissection.

A 54-year-old man who suffered from paraplegia due to type B aortic dissection was treated with a Valiant stent-graft. However, attempts to gain secure proximal sealing resulted in an inadvertent coverage of the left common carotid artery by the endograft. The blood flow in the left common carotid artery was restored by a transcarotid Smart Control stent in a chimney fashion. At 6- and 18-month follow-up, computed tomography scan showed that the chimney stent was severely compressed by the stent graft, although the patient remained neurologically asymptomatic.

Comparison of beraprost and ticlopidine in Chinese patients with chronic peripheral arterial occlusion: a multicenter, single-blind, randomized, controlled study

BACKGROUND Chronic peripheral arterial occlusion (CPAO) is a progressive disease that is associated with a variety of symptoms, the 4 most common being a sensation of coolness in the limbs, intermittent claudication (in which pain occurs on walking), limb pain (which occurs spontaneously at rest), and ischemic leg ulcers. Beraprost sodium is an oral prostaglandin I2 analogue that may ameliorate these symptoms. OBJECTIVE The aim of this study was to compare the efficacy and tolerability of beraprost sodium and ticlopidine hydrochloride in the treatment of patients with CPAO in China. METHODS In this multicenter, single-blind, controlled study, patients with CPAO were randomly assigned to receive beraprost 120-μg tablet TID or ticlopidine 500-mg tablet BID, both administered orally. The clinical efficacy of the drugs was assessed using the 4 main symptoms of CPAO. Ankle-brachial index (ABI) also was measured as a clinical pharmacologic procedure. Adverse events were assessed throughout the study. RESULTS A total of 124 patients (96 men, 28 women; mean [SD] age, 65 [12] years) were enrolled in 3 hospitals. Data from 119 patients (93 men, 26 women; mean [SD] age, 65 [12] years) were included in the efficacy analysis (64 and 55 patients in the beraprost and ticlopidine groups, respectively). Although all 4 symptoms of CPAO were ameliorated after 3 and 6 weeks of treatment with both drugs, only the cool sensation was significantly improved with beraprost compared with ticlopidine at 6 weeks (P<0.05). ABI was significantly increased with both beraprost and ticlopidine at 6 weeks versus baseline (P<0.001 and P<0.01, respectively), suggesting that this pharmacologic action may have led to their beneficial effect on various symptoms. The tolerability analysis included 123 patients (65 and 58 patients in the beraprost and ticlopidine groups, respectively). The numbers of patients who (1) experienced adverse events (AEs), (2) experienced adverse drug reactions, and (3) withdrew due to AEs were significantly smaller in the beraprost group than in the ticlopidine group (P<0.001, P<0.05, and P<0.05, respectively). CONCLUSIONS In this study population of patients with CPAO, beraprost ameliorated cool sensation in the limbs, intermittent claudication, limb pain, and ischemic/leg ulcers. Beraprost was more efficacious in relieving CPAO symptoms and was better tolerated than ticlopidine. Beraprost may be useful for the treatment of patients with CPAO, but more studies are needed.

A Five‐Year Study of the Efficacy of Purified CD34+ Cell Therapy for Angiitis‐Induced No‐Option Critical Limb Ischemia

Angiitis‐induced critical limb ischemia (AICLI) patients constitute a remarkable proportion of no‐option critical limb ischemia (CLI) patients. Stem cell therapy has become an innovative and promising option for no‐option CLI patients. As one of these promising stem cell therapies, purified CD34+ cell transplantation (PuCeT) has shown favorable short‐term results. However, the long‐term efficacy of PuCeT has yet to be reported. This study evaluates the long‐term efficacy of PuCeT in AICLI patients. Twenty‐seven AICLI patients were enrolled from May 2009 to December 2011. Granulocyte colony‐stimulating factor (G‐CSF) and enoxaparin sodium were administered for 5 days. On day 5, CD34+ cell isolation was performed, and cells were transplanted by intramuscular injection. The primary endpoint, major‐amputation‐free survival rate (MAFS), as well as secondary endpoints, such as peak pain‐free walking time (PPFWT) and the Wong‐Baker FACES pain rating scale score (WFPRSS), were routinely evaluated during the 5‐year follow‐up period. The endpoints were as follows: the MAFS was 88.89%; PPFWT increased from 3 ± 3 to 17 ± 6 minutes; WFPRSS decreased from 7 ± 2 to 0.3 ± 1.7; the ulcer healing rate was 85.71%; the recurrence rate was 11.11%; and SF‐36v2 scores were significantly improved at 5 years after PuCeT. The rate of labor recovery 5 years after PuCeT was 65.38%, and no severe adverse effect was observed during the treatment. PuCeT demonstrated long‐term efficacy and durability as a treatment of AICLI not only in achieving limb salvage but also in recovering the labor competence and improving the quality of life of patients. Stem Cells Translational Medicine 2018;7:583–590