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Background: Endothelial injury is considered critical for progression of atherosclerosis and its complications in coronary artery disease (CAD). The endothelial-supportive effects of bradykinin have mainly been attributed to activation of the resident endothelium. Here we newly investigate the role of bradykinin and its B2 receptor for the recruitment and functional activation of circulating mononuclear cell subsets with endothelial-repair promoting capacity, such as CD34(+)CXCR4(+)cells, at sites of arterial injury.Methods and Results: Bradykinin-B2-receptor (B2R) blockade by icatibant substantially impaired recruitment of circulating CD34(+)CXCR4(+) mononuclear cells (expressing high levels of B2R) to endothelial cells in vitro and to injured arterial wall in vivo, whereas recruitment of CD14(hi) monocytes (expressing low levels of B2R) was unchanged. Moreover, the capacity of genetically B2R-deficient bone marrow cells to promote endothelial repair in vivo was markedly impaired as compared with wild-type bone marrow cells. B2R expression was reduced on CD34(+)CXCR4(+)mononuclear cells and endothelial repair-promoting early outgrowth cells, but not on CD14(hi)monocytes, from CAD patients as compared with healthy subjects. B2R stimulation induced CD18 activation in early outgrowth cells of healthy subjects, but not in early outgrowth cells of CAD patients. Adenoviral B2R overexpression enhanced in vivo vascular recruitment and rescued impaired endothelial repair capacity of early outgrowth cells from CAD patients.Conclusions: We newly report that bradykinin/B2R signaling may promote endothelial repair after arterial injury by selective recruitment and functional activation of B2R-expressing circulating mononuclear cell subsets. In CAD patients, B2R downregulation on endothelial repair-promoting circulating mononuclear cells substantially impairs the bradykinin-dependent endothelial repair, representing a novel mechanism promoting endothelial injury in CAD patients. [ABSTRACT FROM AUTHOR]

Mechanical support options for children and small adolescents with acute left ventricular failure are often limited to extracorporeal life support (ECLS) and subsequent left ventricular assist device implantation. We report a case of a 3-year-old child weighing 12 kg with acute humoral rejection after cardiac transplantation not adequately responding to medical therapy who presented in persistent low cardiac output syndrome. We successfully stabilized the patient by implanting a Impella 2.5 device via a 6-mm Hemashield prosthesis on the right axillary artery. The patient was bridged to recovery., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objective: The aim was to report mid-term performance of decellularized equine pericardium used for repair of various congenital heart defects in the pediatric population., Methods: A retrospective review of all patients undergoing patch implantation between 2016 - 2020 was performed. Patch quality, surgical handling, hemostasis and early patch-related complications were studied on all patients. Mid-term performance was observed in patients with ≥12 months follow-up and intact patch at discharge (without reoperation/stent implantation)., Results: A total of 201 patients with median age of 2.5 years [interquartile range (IQR): 0.6-6.5] underwent 207 procedures at 314 implant locations. The patch was used in following numbers/locations: 171 for pulmonary artery (PA) augmentation, 36 for aortic repair, 35 for septal defect closure, 22 for valvular repair and 50 at other locations. Early/30-day mortality was 6.5%. Early patch-related reoperations/stent implantations occurred in 28 locations (8.9%). No patch-related complications were noted except for bleeding from implant site in three locations (1%). Follow-up ≥ 12 months was available for 132 patients/200 locations. During a median follow-up of 29.7 months [IQR: 20.7-38.3], 53 patch-related reoperations/catheter reinterventions occurred (26.5%) with the majority in PA position (88.7%, 47/53). Overall 12- and 24-months freedom from patch-related reoperation/catheter reintervention per location was 91.5% (95% CI: 86.7%-94.6%) and 85.2% (95% CI: 78.9%-89.6%) respectively., Conclusion: Decellularized equine pericardium used for repair of various congenital heart defects showed acceptable mid-term performance. Reoperation/reintervention rates were in a range as observed with other xenogeneic materials previously reported articles, occurring most frequently after PA augmentation., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Inflammasomes are crucial gatekeepers of the immune response, but their maladaptive activation associates with inflammatory pathologies. Besides canonical activation, monocytes can trigger non-transcriptional or rapid inflammasome activation that has not been well defined in the context of acute myocardial infarction (AMI). Rapid transcription-independent inflammasome activation induced by simultaneous TLR priming and triggering stimulus was measured by caspase-1 (CASP1) activity and interleukin release. Both classical and intermediate monocytes from healthy donors exhibited robust CASP1 activation, but only classical monocytes produced high mature interleukin-18 (IL18) release. We also recruited a limited number of coronary artery disease (CAD, n=31) and AMI (n=29) patients to evaluate their inflammasome function and expression profiles. Surprisingly, monocyte subpopulations isolated from blood collected during percutaneous coronary intervention (PCI) from AMI patients presented diminished CASP1 activity and abrogated IL18 release despite increased NLRP3 gene expression. This unexpected attenuated rapid inflammasome activation was accompanied by a significant increase of TNFAIP3 and IRAKM expression. Moreover, TNFAIP3 protein levels of circulating monocytes showed positive correlation with high sensitive troponin T (hsTnT), implying an association between TNFAIP3 upregulation and the severity of tissue injury. We suggest this monocyte attenuation to be a protective phenotype aftermath following a very early inflammatory wave in the ischemic area. Damage-associated molecular patterns (DAMPs) or other signals trigger a transitory negative feedback loop within newly recruited circulating monocytes as a mechanism to reduce post-injury tissue damage., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Giral, Franke, Moobed, Müller, Lübking, James, Hartung, Kuschnerus, Meteva, Seppelt, Jakob, Klingenberg, Kränkel, Leistner, Zeller, Blankenberg, Zimmermann, Haghikia, Lüscher, Akalin, Landmesser and Kratzer.)

Objectives: The aim of this study was to report our initial experience when using Matrix Patch™ a cell-free equine-derived pericardium for the augmentation of branch pulmonary arteries (PAs) in children., Methods: Between September 2016 and September 2019, Matrix Patch was used for the augmentation of branch PAs in 96 patients and implanted in 147 separate locations. The median age at implantation was 3.2 years (interquartile range: 0.9-8.4), and 33% of patients were infants. The patch was used mainly in redo surgeries (89.6%). Intra-procedural feasibility and reinterventions were analysed. Primary end points were death or patch-related reoperation/stent implantation. Explanted patches were stained for recellularization/calcification, or to reveal proliferation/inflammation., Results: A total of 81 patients, who received patches in 119 separate locations, were followed within a median of 20 months (interquartile range: 10.2-30.2). Patients with early reoperation/stent implantation were excluded from follow-up. No patch-related death was noted. Survival at last follow-up was 88% (95% CI: 78.8-93.7%). Overall probability of freedom from reoperation/stent implantation per location, 12 and 24 months after initial surgery was 85.8% (95% CI: 76.2-91.7%) and 78.7 (95% CI: 65.9-87.2%), respectively. At 20 months, superficial proliferation with discrete macrophage activity was seen in explants; however, no signs of calcification are observed., Conclusions: The initial experience with the Matrix Patch in PAs showed comparable results to other xenogeneic patch materials. Long-term follow-up data are needed to prove the desired durability of the patch in different locations., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Aggravated endothelial injury and impaired endothelial repair capacity contribute to the high cardiovascular risk in patients with type 2 diabetes (T2D), but the underlying mechanisms are still incompletely understood. Here we describe the functional role of a mature form of miRNA (miR) 483-3p, which limits endothelial repair capacity in patients with T2D. Expression of human (hsa)-miR-483-3p was higher in endothelial-supportive M2-type macrophages (M2MΦs) and in the aortic wall of patients with T2D than in control subjects without diabetes. Likewise, the murine (mmu)-miR-483* was higher in T2D than in nondiabetic murine carotid samples. Overexpression of miR-483-3p increased endothelial and macrophage apoptosis and impaired reendothelialization in vitro. The inhibition of hsa-miR-483-3p in human T2D M2MΦs transplanted to athymic nude mice (NMRI- Foxn1 ν /Foxn1 ν ) or systemic inhibition of mmu-miR-483* in B6.BKS(D)- Lepr db /J diabetic mice rescued diabetes-associated impairment of reendothelialization in the murine carotid-injury model. We identified the endothelial transcription factor vascular endothelial zinc finger 1 (VEZF1) as a direct target of miR-483-3p. VEZF1 expression was reduced in aortae of diabetic mice and upregulated in diabetic murine aortae upon systemic inhibition of mmu-483*. The miRNA miR-483-3p is a critical regulator of endothelial integrity in patients with T2D and may represent a therapeutic target to rescue endothelial regeneration after injury in patients with T2D., (© 2018 by the American Diabetes Association.)

Impaired functions of vascular cells are responsible for the majority of complications in patients with type 2 diabetes (T2D). Recently a better understanding of mechanisms contributing to development of vascular dysfunction and the role of systemic inflammatory activation and functional alterations of several secretory organs, of which adipose tissue has more recently been investigated, has been achieved. Notably, the progression of vascular disease within the context of T2D appears to be driven by a multitude of incremental signaling shifts. Hence, successful therapies need to target several mechanisms in parallel, and over a long time period. This review will summarize the latest molecular strategies and translational developments of cardiovascular therapy in patients with T2D.

Endothelial injury and dysfunction (ED) represent a link between cardiovascular risk factors promoting hypertension and atherosclerosis, the leading cause of death in Western populations. High-density lipoprotein (HDL) is considered antiatherogenic and known to prevent ED. Using HDL from children and adults with chronic kidney dysfunction (HDL(CKD)), a population with high cardiovascular risk, we have demonstrated that HDL(CKD) in contrast to HDL(Healthy) promoted endothelial superoxide production, substantially reduced nitric oxide (NO) bioavailability, and subsequently increased arterial blood pressure (ABP). We have identified symmetric dimethylarginine (SDMA) in HDL(CKD) that causes transformation from physiological HDL into an abnormal lipoprotein inducing ED. Furthermore, we report that HDL(CKD) reduced endothelial NO availability via toll-like receptor-2 (TLR-2), leading to impaired endothelial repair, increased proinflammatory activation, and ABP. These data demonstrate how SDMA can modify the HDL particle to mimic a damage-associated molecular pattern that activates TLR-2 via a TLR-1- or TLR-6-coreceptor-independent pathway, linking abnormal HDL to innate immunity, ED, and hypertension., (Copyright © 2013 Elsevier Inc. All rights reserved.)