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Aortic pathologies, particularly aneurysms and dissections, are associated with high mortality, but their underlying biological mechanisms remain poorly understood. Vascular smooth muscle cells (VSMCs), which are essential for aortic wall stability, originate from different embryological sources—namely, neural crest (NC) and paraxial mesoderm (PM)—which anatomically correspond to the thoracic and abdominal aorta, respectively. The central hypothesis of this study is that these embryonic origins influence the cellular response to mechanical stress, thereby contributing to region-specific differences in aortopathies.

Human induced pluripotent stem cells (iPSCs) were differentiated into NC- and PM-derived progenitor cells and further into VSMCs. The control cells included primary human aortic smooth muscle cells (HASMCs). The cells were then exposed to cyclic equibiaxial stretch (1 Hz, 20% elongation, 24 h) using the Flexcell FX-6000T system on fibronectin- or laminin-coated Bioflex plates. Subsequent to this, mRNA sequencing (mRNA-Seq) using NGS was performed on both undifferentiated and differentiated HASMCs to characterize gene expression changes induced by mechanical stress

Distinct transcriptional responses to mechanical stretch were observed between undifferentiated and differentiated HASMCs. In differentiated cells, stretch induced activation of lipid synthesis pathways, metabolic reprogramming, and transcriptional changes in ribosomal RNA, indicating a shift in protein synthesis activity. In undifferentiated HASMCs, mechanical stretch induced cellular senescence pathways, as well as alterations in immune-related and protein homeostasis pathways. These results suggest that mechanical stretch induces different biological responses depending on the maturation state of the VSMCs. Preliminary data from NC- and PM-derived progenitor cells confirmed successful lineage-specific differentiation and suggested that embryonic origin also influences mechanotransduction

Our findings demonstrate that both differentiation status and embryological origin shape the cellular response to mechanical stimuli. These mechanistic insights highlight the importance of lineage-specific modeling in aortic disease and may support the identification of new biomarkers and therapeutic strategies tailored to region-specific aortic pathologies

Postoperative organ complications following open thoracoabdominal aortic aneurysm (TAAA) repairs pose significant challenges during the early postoperative period, where prompt detection is crucial for improving patient outcomes. Sepsis is often a central factor in these complications. This study investigates the perioperative dynamics of soluble urokinase plasminogen activator receptor (suPAR) plasma levels in TAAA patients undergoing elective surgical repair and evaluates its diagnostic potential for early detection of postoperative sepsis.

In this retrospective, single-center study, 28 patients (mean age 52.6 ± 13.4 years; 67.9% male) underwent elective open TAAA repair between 2022 and 2024. Blood samples were collected at five perioperative time points, and suPAR levels were measured using ELISA. The primary endpoint was the onset of postoperative sepsis, with secondary endpoints including other organ complications. The predictive performance of suPAR levels was evaluated using Receiver Operator Characteristics (ROC) analysis.

Postoperative sepsis developed in 7 of 28 patients (25%), with diagnostic criteria met at a mean of 9.7 ± 6.9 days. Baseline suPAR levels did not differ between groups; however, from 12 hours postoperatively, the sepsis group exhibited significantly higher levels (14.43 ng/ml vs. 7.23 ng/ml; p = 0.004), a difference that persisted through the first 24 hours. At 24 hours, suPAR had the highest predictive accuracy for sepsis, with an AUC of 0.90, 90% sensitivity, and 86% specificity at a 9 ng/ml cut-off (p < 0.001).

Elevated suPAR levels in the early postoperative period are strongly associated with the later onset of sepsis. Early monitoring may enable timely intervention, potentially improving outcomes in this high-risk population.

Abdominal aortic aneurysm (AAA) affects 5% of males over 65 years of age, with a devastating mortality rate of 80% upon rupture. There is no treatment to slow down the progression of AAA. Time-restricted feeding (TRF) involves restricting eating to a certain number of hours per day, typically within a 4- to 12-hour window. TRF has been shown to improve cardiometabolic health in patients with metabolic syndrome. This study aimed to investigate the effects of TRF in a mouse model of AAA.

AAA was induced by topical elastase application in 10 weeks old and 12 months old male WT C57BL/6 mice. β-Aminopropionitrile fumarate was administered post-surgery in drinking water to enhance AAA growth. Seven days post-surgery, the animals were randomly divided into control and early TRF (eTRF) groups. eTRF mice had access to food from zeitgeber time (ZT) 12 to 20. Organs were collected after 2 weeks of eTRF. RNA-seq and immunohistochemistry-paraffin were performed on the AAA.

eTRF slowed down weight gain compared to control mice and improved metabolic profiles, including lower triglyceride and cholesterol levels and better glucose tolerance. RNA-seq analysis revealed that eTRF did not affect the native aorta but increased lipid synthesis pathways in AAA. In eTRF mice, RNA-seq analysis also showed a reduction in inflammatory response and downregulation of genes associated with matrix remodeling in the AAA wall. Additionally, immunohistochemistry-paraffin of AAA tissues demonstrated reduced elastin degradation, decreased vascular smooth muscle cell loss, and lower macrophage and neutrophil infiltration, leading to a reduction in AAA size. In older mice, eTRF also reduced AAA size.

In conclusion, eTRF has a beneficial effect on the progression of AAA likely through reductions in inflammation and vascular remodeling.

The baroreflex is a key mechanism for regulating blood pressure and heart rate, mediated by mechanosensitive baroreceptors in the aortic arch and carotid sinus. However, current knowledge about baroreceptors is derived almost exclusively from animal studies. To date, no data focusing on the molecular nature of human aortic baroreceptors have been reported. We therefore conducted extensive histological, proteomic, and transcriptomic analyses of the human aortic arch and aorta to identify putative baroreceptors.

Three healthy human aortic arches, six abdominal aortic aneurysm samples, and four control abdominal aortic tissue samples from our vascular biobank were analyzed. Immunohistochemistry was performed using antibodies targeting various neuronal markers. Proteomic and transcriptomic analyses were conducted on the macrodissected adventitial layer containing nerves, in collaboration with the Functional Genomics Center Zurich.

Histological analysis revealed a heterogeneous distribution of nerves in the adventitia throughout the aortic arch, with the highest density observed in the ascending aorta up to the left subclavian artery. Proteomic analysis identified three putative baroreceptor candidates—PIEZO1, TRPV2, and TRPM4—in the human aortic arch, abdominal aortic aneurysms, and control abdominal aortas. Notably, none of these candidates were detected in the transcriptomic analysis.

To our knowledge, this is the first study to identify potential baroreceptor proteins in the human aortic arch and aorta, with no significant differences in their expression among the samples. The absence of corresponding RNA transcripts in the adventitia suggests that these genes may be transcribed and translated in the neuronal cell bodies located in the brainstem.
Further research is needed to validate these findings and to elucidate the functional role of these candidate baroreceptors in regulating blood pressure and heart rate in the human aortic arch.

Surgical revascularizations (CABG/vascular peripheral/AV shunts) are performed with autologous arteries and/or veins due to poor clinical patency results of synthetic commercial small-calibre (<6mm ID) vascular prostheses (ePTFE), mainly due to early thrombosis and late intimal hyperplasia. Therefore, we have developed a dual-action coating which is anti-thrombogenic and endothelial cell-favouring.

Our dual-action coating is based on cell-favouring layer-by-layer (LbL) coating with endpoint attached heparin. The coating was applied to small calibre ePTFE vascular grafts (Advanta, Getinge) and compared to uncoated (Advanta, Getinge) as well as two clinically used heparin-coated ePTFE grafts (Propaten, Gore / FlowLine Bipore, Jotec, Artivion). In vitro tests included: mechanical, sterilization and coagulation tests (thrombin time /partial thrombin time / anti-Xa assays) as well as thrombin generation tests up to 14-days. Endothelial cell cultures were performed up to 7 days. Pulsatile perfusion tests for 2/4h with water / NaCl / plasma were performed for assessing the stability of the coating.

Our LbL coating reduces the contact angle from 114-117° to 33-35° therefore making the surface more hydrophylic and thus increasing biocompatibility. The in vitro coagulation tests showed heparin (anti-Xa) in the LbL coated grafts and no thrombin generation. The uncoated grafts showed no heparin but clot formations. The commercial heparin coated grafts showed high thrombin generation under static and dynamic conditions. Figure 1 shows ETP (endogenous thrombin potential / nM.min) values for the various tested grafts after 30’, 1-, 7-, 10- and 14-days incubation compared to our LbL coating which demonstrated absence of thrombin generation up to 10 days. Endothelial cell proliferation was better on LbL coated grafts at 3-7 days in cell culture compared to uncoated grafts.

The in vitro anti-thrombotic and endothelial cell proliferating effects on small calibre ePTFE vascular grafts of our novel dual-action coating have shown promising results which would allow their application for small calibre revascularization procedures such as coronary, peripheral vascular and access surgery for hemodialysis. Furthermore, such a coating could be applied to all MedTech devices in contact with blood.

Hemodynamic forces are sensed at cellular junctions by mechanosensitive proteins like AmotL2 or LGN. These proteins interact with VE-cadherin in a phosphorylation-dependent manner, ensuring proper alignment of the cell along the flow axis. Impaired sensing of flow causes incorrect alignment and a disturbed integrity of the endothelial cell layer which is suggested to contribute to aortic inflammation. Previous results show that gut microbiota-derived short-chain fatty acids such as butyrate, in addition to their known anti-inflammatory properties, also influence the phosphorylation of VE-cadherin and endothelial integrity. It remains to be clarified if this also occurs under laminar flow conditions. Here we address this subject by investigating the impact of butyrate and propionate on VE-cadherin phosphorylation and its interaction with AmotL2 under laminar flow conditions.

Human aortic endothelial cells were cultured under static conditions or exposed to laminar shear stress at 4 dyn/cm^2 or 10 dyn/cm^2 in the presence or absence of butyrate and propionate. The level of VE-cadherin phosphorylation as well and the binding of AmotL2 to VE-cadherin were analyzed by Western blotting and co-immunoprecipitation. Cell alignment and polarization relative to the flow direction in the presence or absence of butyrate were assessed by phase contrast and fluorescence microscopy detecting the Golgi marker GM-130.

Butyrate elevated shear stress dependent phosphorylation of tyrosine 658 of VE-cadherin, most significantly at 10 dyn /cm^2. In the presence of butyrate, AmotL2 protein level were slightly increased. Elevated AmotL2 did not increase the VE-cadherin-bound fraction of AmotL2. Instead, butyrate rather interfered with the binding of AmotL2 to VE-cadherin. Interestingly, preliminary data indicate that propionate also impaired the binding of AmotL2 to VE-cadherin. Moreover, butyrate treatment reduced the number of aligned and polarized cells, most significantly at 4 dyn/cm^2 compared to 10 dyn/cm^2.

Given their known anti-inflammatory effects, we speculate that butyrate and propionate may have an ambivalent role, impairing cell alignment and potentially disrupting mechanosensing, which could trigger inflammation. Ongoing experiments aim to confirm these findings and clarify the role of SCFAs in mechanosensing.

Most atherosclerosis-prone blood vessels are surrounded by perivascular adipose tissue (PVAT), which is contiguous with the adventitial layer of arteries. PVAT is a physiologically and metabolically active endocrine tissue that influences vascular biology through paracrine signaling. The focus here is on adipose tissue macrophages (ATMs) within PVAT. By switching from an anti-inflammatory M2 phenotype to a pro-inflammatory M1 phenotype or vice versa depending on the microenvironment, they play a central role in initiation, maintenance, and resolution of inflammation. The receptor ChemR23 appears crucial for this ATM phenotype switching and for the crosstalk between PVAT and arteries during atherosclerosis.

We use an atherosclerotic mouse model with a systemic ChemR23 knockout expressing eGFP (Apoe-/- ChemR23-knockout/knockin mice). These mice are fed a normal chow diet or a cholesterol rich diet (WD) for 4 weeks. PVAT is analyzed by flow cytometry for ATMs and their phenotype. FACS-sorted myeloid cells (CD45+CD11b+) from PVAT are examined at transcriptomic level using scRNA sequencing. Additionally, a Cre-lox mouse model with a myeloid cell-specific ChemR23 knockout on an Apoe-/- background will allow us to better understand adipocyte-macrophage interactions during vascular and adipose tissue inflammation.

We found that the systemic ChemR23 knockout decreased the number of macrophages in various adipose tissues, including pericardial and epididymal AT as well as periaortic adipose tissue (PVAT) after 4 weeks on WD. Furthermore, the number of M1 macrophages increased in adipose tissues of mice lacking the ChemR23 receptor after 4 weeks on WD.

Based on these data, we hypothesize that the loss of ChemR23 expression adversely affects the phenotype switching of ATMs in PVAT in hyperlipidemic mice during atherosclerosis. Further investigations are planned to explore PVAT immune cell types and their immunometabolic influence on the aorta during homeostasis and inflammation applying spatial biology using the MACSima™ Imaging Cyclic Staining (MICS) technology and flow cytometry.