Gelatin hydrogel crosslinked by microbial transglutaminase (mTG) exhibits excellent performance in cell adhesion, proliferation, and differentiation. We examined the gelation time and gel strength of gelatin/mTG hydrogels in various proportions to investigate their physical properties and tested their degradation performancesin vitro. Cell morphology and viability of adipose tissue-derived stromal cells (ADSCs) cultured on the 2D gel surface or in 3D hydrogel encapsulation were evaluated by immunofluorescence staining. Cell proliferation was tested via Alamar Blue assay. To investigate the hydrogel effect on cell differentiation, the cardiac-specific gene expression levelsof Nkx2.5, Myh6, Gja1, and Mef2c in encapsulated ADSCs with or without cardiac induction medium were detected by real-time RT-PCR. Cell release from the encapsulated status and cell migration in a 3D hydrogel model were assessedin vitro. Results show that the gelatin/mTG hydrogels are not cytotoxic and that their mechanical properties are adjustable. Hydrogel degradation is related to gel concentration and the resident cells. Cell growth morphology and proliferative capability in both 2D and 3D cultures were mainly affected by gel concentration. PCR result shows that hydrogel modulus together with induction medium affects the cardiac differentiation of ADSCs. The cell migration experiment and subcutaneous implantation show that the hydrogels are suitable for cell delivery.

Atrial fibrillation (AF) is a frequent arrhythmia associated with cardiovascular morbidity and mortality. Neutrophil extracellular traps (NETs) are DNA fragments with cytoplasm proteins released from neutrophils, which are involved in various cardiovascular diseases. To elucidate the role of NETs in AF, we investigated the effect of NETs on AF progression and the secretion of NETs in AF. Results showed that: NETs induced the autophagic apoptosis of cardiomyocytes, and NETs also led to mitochondrial injury by promoting mitochondrial depolarization and ROS production. Ongoing tachy-pacing led to the structural loss of cardiomyocytes and provided potent stimuli to induce NETs secretion from neutrophils. In the meanwhile, increased Ang II in AF facilitated NETs formation through the upregulation of AKT phosphorylation, while it could not directly initiate NETosis as the autophagy was not induced. In vivo, DNase I was administrated to abrogate NETs formation, and AF-related fibrosis was ameliorated as expected. Correspondingly, the duration of the induced AF was reduced. Our study addresses the formation mechanism of NETs in AF and demonstrates the lethal effects of NETs on cardiomyocytes through the induction of mitochondrial injury and autophagic cell death, which comprehensively describes the positive feedback comprised of NETs and stimuli secreted by cardiomyocytes that sustains the progression of AF and AF related fibrosis.

Background: Atherosclerosis is now recognized as a chronic inflammatory disease. Angiotensin II (Ang II) is a critical factor in inflammatory responses, which promotes the pathogenesis of atherosclerosis. Placental growth factor (PlGF) is a member of the vascular endothelial growth factor (VEGF) family cytokines and is associated with inflammatory progress of atherosclerosis. However, the potential link between PlGF and Ang II has not been investigated. In the current study, whether Ang II could regulate PlGF expression, and the effect of PlGF on cell proliferation, was investigated in human vascular endothelial cells (VECs) and smooth muscle cells (VSMCs). Results: In growth-arrested human VECs and VSMCs, Ang II induced PlGF mRNA expression after 4 hour treatment, and peaked at 24 hours. 10^-6 mol/L Ang II increased PlGF protein production after 8 hour treatment, and peaked at 24 hours. Stimulation with Ang II also induced mRNA expression of VEGF receptor-1 and -2(VEGFR-1 and -2) in these cells. The Ang II type I receptor (AT₁R) antagonist blocked Ang II-induced PlGF gene expression and protein production. Several intracellular signals elicited by Ang II were involved in PlGF synthesis, including activation of protein kinase C, extracellular signal-regulated kinase 1/2 (ERK1/2) and PI3-kinase. A neutralizing antibody against PlGF partially inhibited the Ang II-induced proliferation of VECs and VSMCs. However, this antibody showed little effect on the basal proliferation in these cells, whereas blocking antibody of VEGF could suppress both basal and Ang II-induced proliferation in VECs and VSMCs. Conclusion: Our results showed for the first time that Ang II could induce the gene expression and protein production of PlGF in VECs and VSMCs, which might play an important role in the pathogenesis of vascular inflammation and atherosclerosis.

Background: Intestinal barrier dysfunction would lead to a rigorous inflammatory reaction due to the translocation of intestinal lumen-derived bacteria and endotoxins. The aim of the present study was to investigate whether intestinal barrier dysfunction occurs in patients with acute Stanford type A aortic dissection (ATAAD) and to determine its potential relationship with the plasma levels of several inflammatory biomarkers in the progression of ATAAD. Design and Methods: Serum samples from a total of 46 patients with ATAAD and 36 healthy volunteers were prospectively collected and analyzed. The serum levels of diamine oxidase (DAO), lactate dehydrogenase (LDH), interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), and C-reactive protein (CRP) were measured using colorimetric assay, enzyme-linked immunosorbent assay, and immunoturbidimetric assay. Results: Serum levels of DAO, LDH, IL-6, TNF-α, and CRP in patients with ATAAD were significantly higher than those in healthy participants. A significantly positive correlation between DAO activity and IL-6 ( r = .56, P < .001), TNF-α ( r = .63, P < .001), and CRP ( r = .53, P < .001) was observed. Moreover, the activity of DAO correlated negatively with the Pao₂/fraction of inspired oxygen (Fio₂) ratio ( r = −.39, P = .007). Conclusions: Intestinal barrier dysfunction, reflected by an increased level of serum DAO, may play an important role in the development of systemic inflammatory responses in patients with ATAAD. Therefore, strategies of preserving a normal intestinal barrier function may open new horizons in the treatment of inflammation-related adverse events in the setting of ATAAD.

Many countries and regions have established multicenter registration studies to improve the outcomes of acute type A aortic dissection (ATAAD). The aims of this study were to report actual preoperative management, surgery type, and early outcomes of surgical treatment for ATAAD in China. This cohort study uses data from the China Registry of Type A Aortic Dissection, a national clinical registry to investigate management of patients with Stanford type A aortic dissection. The data, including surgical management and outcomes of patients with ATAAD, were analyzed from January 2018 to December 2021. A total of 1,058 patients with ATAAD were enrolled in this study between January 2018 and December 2021. The mean age of all patients was 51.6 ±11.7 years. The median interval from onset to hospital was 10.65 hours (IQR: 6-24 hours), and the median interval from entering the emergency room to starting operation was 13 hours (IQR: 4.08-28.7 hours). Total arch repair was performed in 938 patients (88.7%), and frozen elephant trunk repair was performed in 800 patients (75.6%). The incidence of early mortality was 7.6%. The population of patients with ATAAD in China experienced a longer interval from onset to arrival at the hospital, received more extensive aortic arch repair, and showed a relatively lower early mortality. These findings suggest that there may be a huge survivor bias in patients with ATAAD in China, more efforts should be made to promote prehospital emergency care and preoperative management of Chinese ATAAD patients. (A multicenter registration study of aortic dissection in China; ChiCTR1800015338).