Vascular injury activates the ELK1/SND1/SRF pathway to promote vascular smooth muscle cell proliferative phenotype and neointimal hyperplasia.

BACKGROUND: Vascular smooth muscle cell (VSMC) proliferation is the leading cause of vascular stenosis or restenosis. Therefore, investigating the molecular mechanisms and pivotal regulators of the proliferative VSMC phenotype is imperative for precisely preventing neointimal hyperplasia in vascular disease. METHODS: Wire-induced vascular injury and aortic culture models were used to detect the expression of staphylococcal nuclease domain-containing protein 1 (SND1). SMC-specific Snd1 knockout mice were used to assess the potential roles of SND1 after vascular injury. Primary VSMCs were cultured to evaluate SND1 function on VSMC phenotype switching, as well as to investigate the mechanism by which SND1 regulates the VSMC proliferative phenotype. RESULTS: Phenotype-switched proliferative VSMCs exhibited higher SND1 protein expression compared to the differentiated VSMCs. This result was replicated in primary VSMCs treated with platelet-derived growth factor (PDGF). In the injury model, specific knockout of Snd1 in mouse VSMCs reduced neointimal hyperplasia. We then revealed that ETS transcription factor ELK1 (ELK1) exhibited upregulation and activation in proliferative VSMCs, and acted as a novel transcription factor to induce the gene transcriptional activation of Snd1. Subsequently, the upregulated SND1 is associated with serum response factor (SRF) by competing with myocardin (MYOCD). As a co-activator of SRF, SND1 recruited the lysine acetyltransferase 2B (KAT2B) to the promoter regions leading to the histone acetylation, consequently promoted SRF to recognize the specific CArG motif, and enhanced the proliferation- and migration-related gene transcriptional activation. CONCLUSIONS: The present study identifies ELK1/SND1/SRF as a novel pathway in promoting the proliferative VSMC phenotype and neointimal hyperplasia in vascular injury, predisposing the vessels to pathological remodeling. This provides a potential therapeutic target for vascular stenosis.

[Overexpression of connexin 40 (Cx40) inhibits the proliferation of H9c2 cardiomyocytes in rats by cell cycle arrest].

Objective To establish a stable strain of H9c2 cardiomyocytes overexpressing Cx40 and preliminarily investigate the effect of lentiviral vector-mediated Cx40 protein overexpression on the proliferation of H9c2 cells and its related mechanisms. Methods The Cx40 gene fragment was cloned from H9c2 cells by PCR and linked with lentivirus vector pLVX-IRES-Puro to obtain the recombinant plasmid pLVX-Flag-Cx40. Recombinant lentiviral particles carrying Flag-Cx40 were obtained by cotransfection with packaging plasmids into HEK293T cells. A stable expression strain (H9c2-Flag-Cx40 cell) was screened from infected H9c2 cells by purinomycin. The expression of Cx40 protein was detected by Western blot analysis, and the effect of Cx40 on H9c2 cells proliferation was determined by CCK-8 assay; cell cycle changes were measured by flow cytometry; the expression of the cell cycle protein cyclin D1 was detected by qRT-PCR and Western blot analysis. Co-immunoprecipitation (Co-IP) immunoprecipitation and Western blot analysis were used to identify the binding of Cx40 and Yes associated protein (YAP) in H9c2 cells; cytoplasmic and cytosolic proteins were isolated to detect the effect of Cx40 on the localization of YAP using Western blot analysis. Results Sequencing results showed that the recombinant pLVX-Flag-Cx40 expression vector was successfully established. A stable transfected cell line containing recombinant Flag-Cx40 lentivirus (H9c2-Flag-Cx40 cell) was successfully constructed from H9c2 cells. Compared with the control group, overexpression of Cx40 significantly reduced the proliferation of H9c2 cells, arrested the cell cycle at G0/G1 and reduced cyclin D1 expression. A significant increase in YAP expression was observed in the cytoplasm of the H9c2-Flag-Cx40 stable cell line, while the expression in the nucleus was significantly reduced. Cx40 bound to YAP in the cytoplasm and prevented it from entering the nucleus to play the role of transcriptional coactivation. Conclusion Overexpression of Cx40 induces cell-cycle arrest at G0/G1 phase and inhibits the proliferation in H9c2 cells.

[Application of radial artery in total arterial coronary revascularization in elderly patients].

OBJECTIVE: To summarize the application experience and clinical effect of radial artery in total arterial coronary revascularization (TAR) in elderly patients. METHODS: Retrospectively analyzed the clinical data of patients who underwent TAR at the University of Hong Kong Shenzhen Hospital from July 1, 2020 to May 30, 2022. Patients were divided into ≥ 65-year-old group and < 65-year-old group according to age. The radial artery blood flow, diameter, intimal integrity and Allen test were evaluated by ultrasound before operation. The distal ends of radial artery were collected for pathological examination during operation. Coronary artery CT angiography (CTA) was examined postoperatively and follow up. The safety and reliability of ultrasonic assessment of radial artery and application of radial artery in elderly patients with TAR were summarized and analyzed. RESULTS: A total of 101 patients received TAR, including 35 cases aged ≥ 65 years old, 66 cases aged < 65 years old; 78 cases used bilateral radial arteries, and 23 cases used unilateral radial arteries. 4 cases of bilateral internal mammary arteries. All the proximal ends of the radial artery were anastomosed to the proximal end of the ascending aorta, 34 cases were performed of "Y" grafts, and 4 cases were sequential anastomoses. There was no in-hospital death and perioperative cardiovascular events. Perioperative cerebral infarction occurred in 3 patients. 1 patients was reoperated for bleeding. Intra-aortic balloon pump (IABP) assistance was used in 21 patients. Poor wound healing occurred in 2 cases and healed well after debridement. Follow-up of 2 to 20 months after discharge showed no internal mammary artery occlusion and 4 radial artery occlusions; no major adverse cardiovascular and cerebrovascular event (MACCE) occurred, and the survival rate was 100%. There was no significant difference in the above perioperative complications and follow-up endpoints between the two age groups. CONCLUSIONS: By adjusting the order of bypass anastomosis and optimizing the preoperative evaluation method, radial artery combined with internal mammary artery can obtain better outcome early in TAR, and can be safely and reliably applied to elderly patients.

Efficacy of endovascular repair in the treatment of retrograde ascending aortic intramural haematoma.

BACKGROUND: The current treatment for retrograde ascending aortic intramural hematoma (RAIMH) remains challenging. This study aims to summarize the short-term results of endovascular repair in the treatment of retrograde ascending aortic intramural hematoma. METHODS: Between June 2019 and June 2021, 21 patients (16 males and 5 females) with a retrograde ascending aortic intramural hematoma, aged 53 ± 14years, received an endovascular repair in our hospital. All cases involved an ascending aortic or aortic arch intramural hematoma. 15 patients had an ulcer on the descending aorta combined with an intramural hematoma in the ascending aorta and 6 patients had typical dissection changes on the descending aorta combined with an intramural hematoma in the ascending aorta. All patients had a successful endovascular stent-graft repair, with 10 cases operated on in the acute phase (<14 days) and 11 cases in the chronic phase (14-35 days). RESULTS: A single-branched aortic stent graft system was implanted in 10 cases, a straight stent in 2 cases, and a fenestrated stent in 9 cases. All surgeries were technically successful. One of the patients developed a new rupture 2 weeks after surgery and was converted to a total arch replacement. No perioperative stroke, paraplegia, stent fracture or displacement, limb or abdominal organ ischemia occurred. The intramural hematomas started being absorbed on CT angiography images before discharge. There was no incidence of postoperative 30-day mortality, and the intramural hematomas in the ascending aorta and aortic arch were fully or partly absorbed. CONCLUSION: Endovascular repair of retrograde ascending aortic intramural hematoma was shown to be safe and effective, and correlated with favorable short-term results.

Endothelial colony-forming cell-derived exosomal miR-21-5p regulates autophagic flux to promote vascular endothelial repair by inhibiting SIPL1A2 in atherosclerosis.

BACKGROUND: Percutaneous transluminal coronary angioplasty (PTCA) represents an efficient therapeutic method for atherosclerosis but conveys a risk of causing restenosis. Endothelial colony-forming cell-derived exosomes (ECFC-exosomes) are important mediators during vascular repair. This study aimed to investigate the therapeutic effects of ECFC-exosomes in a rat model of atherosclerosis and to explore the molecular mechanisms underlying the ECFC-exosome-mediated effects on ox-LDL-induced endothelial injury. METHODS: The effect of ECFC-exosome-mediated autophagy on ox-LDL-induced human microvascular endothelial cell (HMEC) injury was examined by cell counting kit-8 assay, scratch wound assay, tube formation assay, western blot and the Ad-mCherry-GFP-LC3B system. RNA-sequencing assays, bioinformatic analysis and dual-luciferase reporter assays were performed to confirm the interaction between the miR-21-5p abundance of ECFC-exosomes and SIPA1L2 in HMECs. The role and underlying mechanism of ECFC-exosomes in endothelial repair were explored using a high-fat diet combined with balloon injury to establish an atherosclerotic rat model of vascular injury. Evans blue staining, haematoxylin and eosin staining and western blotting were used to evaluate vascular injury. RESULTS: ECFC-exosomes were incorporated into HMECs and promoted HMEC proliferation, migration and tube formation by repairing autophagic flux and enhancing autophagic activity. Subsequently, we demonstrated that miR-21-5p, which is abundant in ECFC-exosomes, binds to the 3' untranslated region of SIPA1L2 to inhibit its expression, and knockout of miR-21-5p in ECFC-exosomes reversed ECFC-exosome-decreased SIPA1L2 expression in ox-LDL-induced HMEC injury. Knockdown of SIPA1L2 repaired autophagic flux and enhanced autophagic activity to promote cell proliferation in ox-LDL-treated HMECs. ECFC-exosome treatment attenuated vascular endothelial injury, regulated lipid balance and activated autophagy in an atherogenic rat model of vascular injury, whereas these effects were eliminated with ECFC-exosomes with knockdown of miR-21-5p. CONCLUSIONS: Our study demonstrated that ECFC-exosomes protect against atherosclerosis- or PTCA-induced vascular injury by rescuing autophagic flux and inhibiting SIAP1L2 expression through delivery of miR-21-5p. Video Abstract.

Investigation into the role of Stmn2 in vascular smooth muscle phenotype transformation during vascular injury via RNA sequencing and experimental validation.

This study examined the effects of Stmn2 on phenotype transformation of vascular smooth muscle in vascular injury via RNA sequencing and experimental validation. Total RNA was extracted for RNA sequencing after 1, 3 and 5 days of injury to screen the differentially expressed genes (DEGs). Western blot was used to detect the protein expression of Stmn2 and its associated targets. The morphological changes of carotid arteries in rats were examined by hematoxylin and eosin (H&E) staining. The expression of vascular smooth muscle cell (VSMC) phenotype markers smooth muscle alpha-actin (α-SMA), vimentin and OPN were detected by immunohistochemistry. DEGs were related to the extracellular matrix and other cell components outside the plasma membrane. They were associated with protein binding, cytoskeleton protein binding, signal receptor binding and other molecular functions, actin cytoskeleton regulation and other Kyoto Encyclopedia of Genes and Genomes pathways. Stmn2 was identified as the hub gene of actin cytoskeleton pathway and vascular disease, and its expression followed the trend of decreasing initially and increasing afterwards during the progress of vascular injury. Western blot assay showed that the expression of Stmn2 and Tubulin decreased immediately after vascular injury; Stmn2 overexpression significantly up-regulated the expression of osteopontin and α-SMA and vimentin in VSMCs. The results of morphology analysis and immunostaining also showed that Stmn2 overexpression promoted the intima thickening and enhanced the proliferating cell nuclear antigen expression in the injured vascular tissues. In conclusion, our results implied that Stmn2 may play a potential role in vascular injury, which may be associated with VSMC phenotype transformation. Further studies are warranted to determine detailed molecular mechanisms of Stmn2 in vascular injury.

Thoracic Endovascular Repair for Aortic Arch Pathologies with Surgeon Modified Fenestrated Stent Grafts: A Multicentre Retrospective Study.

OBJECTIVE: To evaluate the outcome of thoracic endovascular repair (TEVAR) for aortic arch pathologies with surgeon modified fenestrated stent grafts. METHODS: A multicentre, retrospective study consisting of consecutive patients from seven centres treated with surgeon modified fenestrated stent grafts for aortic arch pathologies was conducted. A technique to align fenestrations and supra-aortic vessels was applied. Rates of technical success, mortality, complications, and re-interventions were evaluated. RESULTS: Between February 2016 and January 2020, 513 consecutive patients with aortic arch pathologies received TEVAR with surgeon modified fenestrated stent grafts. The technical success rate was 98.6% (n = 506). In total, 626 fenestrations were created to revascularise 684 branch arteries of the aortic arch. There were 13 deaths and 15 re-interventions within 30 days of the operation. The estimated clinical success rate at 30 days was 94.4% (95% confidence interval [CI] 92.4 - 96.4), the estimated survival at 30 days was 97.5% (95% CI 96.1 - 98.9), and the estimated freedom from re-intervention at 30 days was 97.1% (95% CI 95.7 - 98.5). The median follow up was 27 (interquartile range 13 - 31) months. During follow up, there were five aortic related deaths, three non-aortic related deaths, and four deaths of unknown cause. Eighteen patients underwent re-intervention. The estimated clinical success rate at 24 months was 88.2% (95% CI 85.5 - 91.0), the estimated survival at 24 months was 94.9% (95% CI 92.7 - 97.1), and the estimated freedom from re-intervention at 24 months was 93.1% (95% CI 91.0 - 95.3). In total, 18 cases of stroke were recorded, including 12 within 30 days and six during follow up; six cases of retrograde type A aortic dissection were recorded, including five within 30 days and one during the follow up. CONCLUSION: TEVAR with surgeon modified fenestrated stent grafts for the treatment of aortic arch pathologies provides acceptable outcomes. Further follow up is required to confirm the benefits of this approach.

Exploration of Simplified Intraluminal TEVAR Technique for the Treatment of Aortic Arch Disease.

OBJECTIVE: The positional relationship between the three branches of the aortic arch was determined in normal people. This study provides data to support the customization of aortic arch stents and simplifies intraluminal treatment. METHODS: From January 2019 to August 2019, 120 patients who met the inclusion criteria were examined by CT angiography. The ratio of the distance from the midpoint of the three-branch opening onto the anterior wall to the cross-sectional diameter of the aortic arch was calculated. The positional relationship among the three-branch openings was obtained and the data were analyzed statistically. RESULTS: The three-branch openings were not in a straight line. The positional relationship among the three-branch openings was divided into four types, which were not statistically different between sex and age (P>0.05). CONCLUSION: By measuring the opening position of the three aortic branches, the positional relationship among the three branches was defined to provide a theoretical basis for the design of intraluminal stents and simplified intracavity thoracic endovascular aortic repair (TEVAR) technology.

Exploration of Simplified Intraluminal TEVAR Technique for the Treatment of Aortic Arch Disease

Abstract Objective: The positional relationship between the three branches of the aortic arch was determined in normal people. This study provides data to support the customization of aortic arch stents and simplifies intraluminal treatment. Methods: From January 2019 to August 2019, 120 patients who met the inclusion criteria were examined by CT angiography. The ratio of the distance from the midpoint of the three-branch opening onto the anterior wall to the cross-sectional diameter of the aortic arch was calculated. The positional relationship among the three-branch openings was obtained and the data were analyzed statistically. Results: The three-branch openings were not in a straight line. The positional relationship among the three-branch openings was divided into four types, which were not statistically different between sex and age (P>0.05). Conclusion: By measuring the opening position of the three aortic branches, the positional relationship among the three branches was defined to provide a theoretical basis for the design of intraluminal stents and simplified intracavity thoracic endovascular aortic repair (TEVAR) technology.

Research on clinical characteristics and prognostic analysis of heparin-induced thrombocytopenia after surgery for acute type a aortic dissection.

PURPOSE: The present study aimed to explore the clinical characteristics of heparin-induced thrombocytopenia (HIT) after surgery for acute type A aortic dissection and perform a relevant prognostic analysis. METHODS: After continuous observation and analysis of 204 patients who underwent acute type A aortic dissection, we found that blood platelets decreased significantly after surgery and that these patients can be suspected to suffer HIT based on relevant 4Ts scores. For these suspected HIT patients, a latex particle-enhanced immunoturbidimetric assay was conducted to detect heparin-induced antibodies. Perioperative clinical data of patients in HIT and non-HIT groups were recorded as were blood platelet counts, HIT antibody test results, 4Ts scores, thromboembolic complications, clinical prognosis and outcomes. RESULTS: In the present study, 38 suspected HIT patients, 16 HIT patients and 188 non-HIT patients were selected in the clinical setting. Among them, HIT patients were found to have prolonged cardiopulmonary bypass time (223 min on average vs. 164 min) and delayed aortic cross-clamp time (128 min on average vs. 107 min), and these differences between HIT patients and non-HIT patients were significant (P < 0.05). Additionally, the HIT group required longer operation time and higher dose of heparin, but showing no statistical differences (P > 0.05). The transfusions of blood platelets in the HIT group and non-HIT group were 18.7 ± 5.0u and 15.6 ± 7.34 u, respectively. In the HIT group, the mechanic ventilation time and the length of ICU stay were longer comparing the non-HIT group(P < 0.05), though no significant differences in total length of stay or In-hospital mortality were observed (P > 0.05). The incidence of continuous renal replacement therapy in HIT group was higher than the non-HIT group (P < 0.05). Additionally,there were no significant differences in 24-h postoperative drainage or reoperation for bleeding in both group(P > 0.05). However, the HIT antibody titer in the HIT group was significantly higher than that in the Suspected HIT group (2.7 ± 0.8 U/mL vs. 0.3 ± 0.2 U/mL) (P < 0.05). Among patients diagnosed with HIT, the incidence of thromboembolism reached 31.5%.For example, two HIT patients newly developed thromboembolism in both lower extremities,and three patients experienced cerebral infarction. CONCLUSIONS: After surgery for acute type A aortic dissection, HIT patients developed postoperative complications, the duration of ventilatory support and length of ICU stay were extended, and the incidence of thromboembolism increased. HIT antibody detection and risk classification should be implemented for high-risk patients showing early clinical characteristics.

Changes in Coagulation and Fibrinolysis Systems During the Perioperative Period of Acute Type A Aortic Dissection.

BACKGROUND: Acute type A aortic dissection (ATAAD) has a high risk of perioperative bleeding and often requires extensive blood product infusions. Analysis of the changes in coagulation and fibrinolysis is both helpful for proper treatment and an improved prognosis. The present study investigated the changes in the coagulation and fibrinolysis systems during the perioperative period of ATAAD. METHODS: Twenty-two patients with ATAAD were included in this study. After diagnosis, all patients underwent ascending aorta replacement, aortic arch replacement, and implantation of a special stented endovascular graft. The control group included 25 patients undergoing elective aortic surgery. Baseline preoperative, intraoperative, and postoperative data were collected in both groups. Venous blood samples of all subjects were collected at five time points, after admission (T1), before surgery (T2), after protamine reversal (T3), postoperative 6 h (T4), and postoperative 24 h (T5), measuring the concentrations of platelet factor 4 (PF4), prothrombin fragment 1 + 2 (F1+2), tissue factor (TF), tissue factor pathway inhibitor (TFPI), plasminogen activator (PA), plasminogen activator inhibitor-1 (PAI-1) and thrombin antithrombin complex (TAT) by enzyme-linked immunosorbent assays (ELISAs). RESULTS: The average age of the ATAAD group was 49.9±12.5 years old, while that of the control group was 57.0±12.1 years old. There were more patients with a smoking history, and the cardiopulmonary bypass time, aortic cross-clamp time, and preoperative left ventricular ejection fraction were higher in the ATAAD group than in the control group (P < 0.05). Additionally, preoperative fibrin degradation products (FDP) and preoperative D-dimer were higher in the ATAAD group than in the control group (P < 0.05). However, time from onset to operation, intraoperative core temperature, preoperative B-type natriuretic peptide (BNP), and left ventricular end-diastolic diameter in the ATAAD group were lower than those in the control group (P < 0.05). In contrast, however, the proportion of abnormal bicuspid aortic valves in the control group was higher (P < 0.05). TF in the ATAAD group was significantly higher at T1 (7.9±3.7 ng/mL versus 0.9±0.7 ng/mL, P < 0.05). The TFPI in the ATAAD group was higher than that in the control group at T1 and T2 (P < 0.05). Additionally, PA in the ATAAD group was higher than that in the control group at T1, T2, T3, and T5 (P < 0.05), while PA in the control group was significantly higher at T3 than at T1 (P < 0.05). There was no significant difference in PAI-1 between the two groups before surgery (P > 0.05). Nevertheless, both groups reached their peak value at T3. The platelet count and fibrinogen (FBG) in the ATAAD group decreased significantly from T1 to T2 and continued to decrease after cardiopulmonary bypass. F1+2 and TAT in the ATAAD group were higher than in the control group (P < 0.05); however, they peaked at T3. The PF4 in the ATAAD group slightly increased at T1, while PF4 at T3 was significantly higher than at T1 (P < 0.05). CONCLUSION: The changes in coagulation and fibrinolysis in the ATAAD group before surgery were very significant, which caused a large amount of fibrinogen and platelet consumption. Cardiopulmonary bypass (CPB) and a lower intraoperative core temperature exacerbated the coagulation and fibrinolysis disorder, and the pro-coagulant function of the platelets was activated after surgery. Maintaining the normal concentration of fibrinogen was helpful to correct the coagulation function disorder.

Translation of Tudor-SN, a novel terminal oligo-pyrimidine (TOP) mRNA, is regulated by the mTORC1 pathway in cardiomyocytes.

The mechanisms that regulate cell-cycle arrest of cardiomyocytes during heart development are largely unknown. We have previously identified Tudor staphylococcal nuclease (Tudor-SN) as a cell-cycle regulator and have shown that its expression level was closely related to cell-proliferation capacity. Herein, we found that Tudor-SN was highly expressed in neonatal mouse myocardia, but it was lowly expressed in that of adults. Using Data Base of Transcription Start Sites (DBTSS), we revealed that Tudor-SN was a terminal oligo-pyrimidine (TOP) mRNA. We further confirmed that the translational efficiency of Tudor-SN mRNA was controlled by the mammalian target of rapamycin complex 1 (mTORC1) pathway, as revealed via inhibition of activated mTORC1 in primary neonatal mouse cardiomyocytes and activation of silenced mTORC1 in adult mouse myocardia; additionally, this result was recapitulated in H9c2 cells. We also demonstrated that the downregulation of Tudor-SN in adult myocardia was due to inactivation of the mTORC1 pathway to ensure that heart growth was in proportion to that of the rest of the body. Moreover, we revealed that Tudor-SN participated in the mTORC1-mediated regulation of cardiomyocytic proliferation, which further elucidated the correlation between Tudor-SN and the mTORC1 pathway. Taken together, our findings suggest that the translational efficiency of Tudor-SN is regulated by the mTORC1 pathway in myocardia and that Tudor-SN is involved in mTORC1-mediated regulation of cardiomyocytic proliferation and cardiac development.

Osteoglycin knockdown promotes vascular smooth muscle cell proliferation and migration in aortic dissection via the VEGF/VEGFR2 axis.

Extracellular matrix (ECM) proteins serve a major role in the pathogenesis of aortic dissection (AD). The aim of the present study was to investigate the effect of osteoglycin (OGN), an ECM proteoglycan, on aortic dissection (AD), as well as the underlying mechanism. Thoracic aortic tissues from 20 patients with AD and healthy thoracic aortic tissue from 5 patients undergoing coronary artery bypass grafting were collected to detect OGN expression levels. Following OGN knockdown in rat aortic smooth muscle cells, cell proliferation was detected by performing Cell Counting Kit­8 and BrdU assays, cell migration was assessed by performing the wound healing assay, cell invasion was detected by performing the Transwell assay, and VEGFR/AKT signaling pathway­related protein expression levels were measured via western blotting. The results demonstrated that OGN expression was significantly downregulated in patients with AD compared with healthy controls. Compared with the si­negative control (NC) group, OGN knockdown promoted RASMC proliferation and migration. Compared with the si­NC group, OGN knockdown also significantly enhanced the phosphorylation of the downstream signaling molecules of VEGFR, including AKT and ERK1/2, in VEGF­stimulated RASMCs. Collectively, the present study indicated that OGN knockdown facilitated RASMC proliferation and migration by activating AKT and ERK1/2 signaling. Therefore, OGN may serve as a novel therapeutic target for AD.

99-Case Study of Sporadic Aortic Dissection by Whole Exome Sequencing Indicated Novel Disease-Associated Genes and Variants in Chinese Population.

BACKGROUND: In this study, the whole exome sequencing in human aortic dissection, a highly lethal cardiovascular disease, was investigated to explore the aortic dissection-associated genes and variants in Chinese population. METHODS: Whole exome sequencing was performed in 99 cases of aortic dissection. All single nucleotide polymorphisms (SNPs), insertions/deletions (InDels), and copy number variations (CNVs) were filtered to exclude the benign variants. Enrichment analysis and disease-gene correlation analysis were performed. RESULTS: 3425873 SNPs, 685245 InDels, and 1177 CNVs were identified, and aortic dissection-associated SNPs, InDels, and CNVs were collected. After the disease correlation analysis, 20 candidate genes were identified. Part of these genes such as MYH11, FBN1, and ACTA2 were consistent with previous studies, while MLX, DAB2IP, EP300, ZFYVE9, PML, and PRKCD were newly identified as candidate aortic dissection-associated genes. CONCLUSION: The pathogenic and likely pathogenic variants in most of AD-associated genes (FBN1, MYH11, EFEMP2, TGFBR2, FBN2, COL3A1, and MYLK) were identified in our cohort study, and pathogenic CNVs involved in MYH11, COL family, and FBN were also identified which are not detectable by other NGS analysis. The correlation between MLX, DAB2IP, EP300, ZFYVE9, PML, PRKCD, and aortic dissection was identified, and EP300 may play a key role in AD.

Hybrid two-stage repair of Stanford A dissection with visceral or peripheral malperfusion.

BACKGROUND: The present study aimed to evaluate the effect of two-stage hybrid aortic repair at the distal aorta of Stanford A dissection with malperfusion. METHODS: This retrospective case series included 20 patients with Stanford A dissection administered two-stage thoracic endovascular aortic repair (TEVAR) about 1 month after central repair because of visceral or limb malperfusion. The patients were examined by computed tomography (CT) angiography at 3, 6, 12 and 24 months after operation. Recovery of malperfusion and true lumen index were evaluated during follow-up. RESULTS: Twenty patients underwent two-stage hybrid aortic repair, including 11 males and 9 females. The follow-up time was 24 ± 7 months. No intervention-related complications were observed, including stent graft-induced new re-entry tears, death, stroke and spinal cord injury. Malperfusion in all cases was corrected. The true lumen was not enlarged enough 1 month after the first surgery. Thrombosis of the false lumen was observed around the elephant trunk at the carina level and the celiac artery. Three months after second stage TEVAR, the false lumen thrombosis was resorbed; in addition, the trunk was fully expanded at the carina level, and the true lumen was enlarged at the celiac artery. CONCLUSIONS: Two-stage hybrid aortic repair for residual true lumen in the distal aorta 1 month after initial surgery is helpful for descending aorta remodeling and effective in treating malperfusion. This procedure may be a good option for patients suffering from Stanford A dissection with small true lumen in the distal aorta and malperfusion.

The Role of miR-107 as a Potential Biomarker and Cellular Factor for Acute Aortic Dissection.

Acute aortic dissection (AD) is one of the most severe and highly mortality vascular disease. Its actual prevalence may be seriously underestimated. We studied different expression genes to understand gene profile change between acute AD and nondiseased individuals, and then discover potential biomarkers and therapeutic targets of acute AD. In our study, acute AD differentially expressed mRNAs and miRNAs were identified through bioinformatics analysis on Gene Expression Omnibus data sets GSE52093, GSE98770, and GSE92427. Then, comprehensive target prediction and network analysis methods were used to evaluate protein-protein interaction networks and to identify Gene Ontology terms for differentially expressed mRNAs. Differentially expressed mRNAs-miRNAs involved in acute AD were assessed as well. Finally, the quantitative real-time PCR and in vitro experiment was used to validate the results. We found Integral Membrane Protein 2C (ITM2C) was low expressed and miR-107-5p was highly expressed in acute AD tissues. Meanwhile, overexpression miR-107-5p promoted the cell proliferation and inhibited the cell apoptosis in RASMC cells. miR-107-5p inhibited the progression of acute AD through targeted ITM2C.