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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.

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.

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.

ObjectivesWe 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.MethodsWe 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.ResultsThe anastomosis and cuff graft groups both increased in systolic pressure, mean pulmonary arterial pressure (P

Recent genome-wide association studies have revealed an association between variation at the ADAMTS7 locus and susceptibility to coronary artery disease (CAD). Furthermore, in a population-based study cohort, we observed an inverse association between atherosclerosis prevalence and rs3825807, a nonsynonymous SNP (A to G) leading to a Ser-to-Pro substitution in the prodomain of the protease ADAMTS7. In light of these data, we sought a mechanistic explanation for this association. We found that ADAMTS7 accumulated in smooth muscle cells in coronary and carotid atherosclerotic plaques. Vascular smooth muscle cells (VSMCs) of the G/G genotype for rs3825807 had reduced migratory ability, and conditioned media of VSMCs of the G/G genotype contained less of the cleaved form of thrombospondin-5, an ADAMTS7 substrate that had been shown to be produced by VSMCs and inhibit VSMC migration. Furthermore, we found that there was a reduction in the amount of cleaved ADAMTS7 prodomain in media conditioned by VSMCs of the G/G genotype and that the Ser-to-Pro substitution affected ADAMTS7 prodomain cleavage. The results of our study indicate that rs3825807 has an effect on ADAMTS7 maturation, thrombospondin-5 cleavage, and VSMC migration, with the variant associated with protection from atherosclerosis and CAD rendering a reduction in ADAMTS7 function.

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 β-catenin and lower β-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.

Rationale: Accumulating evidence indicates that stem/progenitor cells (SPCs) represent an important source of cells in atheromas and contribute to lesion formation and progression. Objective: We investigated whether matrix metalloproteinase-8 (MMP8) played a role in SPC migration and their recruitment into atheromas. Methods and Results: We found that SPCs in atheromas expressed MMP8 and that MMP8 knockout significantly reduced SPC numbers in atherosclerotic lesions in apolipoprotein E (ApoE)–deficient mice fed a Western diet. Further in vivo experiments showed that ApoE −/− /MMP8 −/− mice injected with stem cells isolated from bone marrows of ApoE −/− /MMP8 −/− mice had fewer SPCs in atheromas and smaller lesions than ApoE −/− /MMP8 −/− mice injected with stem cells isolated from bone marrows of ApoE −/− /MMP8 +/+ mice. Ex vivo experiments showed that MMP8 deficiency inhibited the ability of SPCs to migrate from the arterial lumen and the adventitia into atherosclerotic lesions. In vitro assays indicated that MMP8 facilitated SPC migration across endothelial cells and through Matrigel or collagen I. We also found that MMP8 cleaved a-disintegrin-and-metalloproteinase-domain-10 and that MMP8 deficiency reduced mature a-disintegrin-and-metalloproteinase-domain-10 on SPCs. Knockdown of MMP8 or incubation with the a-disintegrin-and-metalloproteinase-domain-10 inhibitor GI254023X decreased E-cadherin shedding on SPCs. The decrease in migratory ability of SPCs with MMP8 knockdown was reduced by incubation of such cells with culture supernatant from SPCs without MMP8 knockdown, and this compensatory effect was abolished by an antibody against soluble E-cadherin. Conclusions: MMP8 plays an important role in SPC migration and their recruitment into atherosclerotic lesions.