Regulation of intestinal immunity and tissue repair by enteric glia.

Tissue maintenance and repair depend on the integrated activity of multiple cell types1. Whereas the contributions of epithelial2,3, immune4,5 and stromal cells6,7 in intestinal tissue integrity are well understood, the role of intrinsic neuroglia networks remains largely unknown. Here we uncover important roles of enteric glial cells (EGCs) in intestinal homeostasis, immunity and tissue repair. We demonstrate that infection of mice with Heligmosomoides polygyrus leads to enteric gliosis and the upregulation of an interferon gamma (IFNγ) gene signature. IFNγ-dependent gene modules were also induced in EGCs from patients with inflammatory bowel disease8. Single-cell transcriptomics analysis of the tunica muscularis showed that glia-specific abrogation of IFNγ signalling leads to tissue-wide activation of pro-inflammatory transcriptional programs. Furthermore, disruption of the IFNγ-EGC signalling axis enhanced the inflammatory and granulomatous response of the tunica muscularis to helminths. Mechanistically, we show that the upregulation of Cxcl10 is an early immediate response of EGCs to IFNγ signalling and provide evidence that this chemokine and the downstream amplification of IFNγ signalling in the tunica muscularis are required for a measured inflammatory response to helminths and resolution of the granulomatous pathology. Our study demonstrates that IFNγ signalling in enteric glia is central to intestinal homeostasis and reveals critical roles of the IFNγ-EGC-CXCL10 axis in immune response and tissue repair after infectious challenge.

Progression of Arterial Vasa Vasorum from Regulator of Arterial Homeostasis to Promoter of Atherogenesis.

The vasa vasorum (vessels of vessels) are a dynamic microvascular system uniquely distributed to maintain physiological homeostasis of the artery wall by supplying nutrients and oxygen to the outer layers of the artery wall, adventitia, and perivascular adipose tissue, and in large arteries, to the outer portion of the medial layer. Vasa vasorum endothelium and contractile mural cells regulate direct access of bioactive cells and factors present in both the systemic circulation and the arterial perivascular adipose tissue and adventitia to the artery wall. Experimental and human data show that proatherogenic factors and cells gain direct access to the artery wall via the vasa vasorum and may initiate, promote, and destabilize the plaque. Activation and growth of vasa vasorum occur in all blood vessel layers primarily by angiogenesis, producing fragile and permeable new microvessels that may cause plaque hemorrhage and fibrous cap rupture. Ironically, invasive therapies, such as angioplasty and coronary artery bypass grafting, injure the vasa vasorum, leading to treatment failures. The vasa vasorum function both as a master integrator of arterial homeostasis and, once perturbed or injured, as a promotor of atherogenesis. Future studies need to be directed at establishing reliable in vivo and in vitro models to investigate the cellular and molecular regulation of the function and dysfunction of the arterial vasa vasorum.

Artery Tertiary Lymphoid Organs Control Aorta Immunity and Protect against Atherosclerosis via Vascular Smooth Muscle Cell Lymphotoxin ß Receptors.

Tertiary lymphoid organs (TLOs) emerge during nonresolving peripheral inflammation, but their impact on disease progression remains unknown. We have found in aged Apoe(-/-) mice that artery TLOs (ATLOs) controlled highly territorialized aorta T cell responses. ATLOs promoted T cell recruitment, primed CD4(+) T cells, generated CD4(+), CD8(+), T regulatory (Treg) effector and central memory cells, converted naive CD4(+) T cells into induced Treg cells, and presented antigen by an unusual set of dendritic cells and B cells. Meanwhile, vascular smooth muscle cell lymphotoxin ß receptors (VSMC-LTßRs) protected against atherosclerosis by maintaining structure, cellularity, and size of ATLOs though VSMC-LTßRs did not affect secondary lymphoid organs: Atherosclerosis was markedly exacerbated in Apoe(-/-)Ltbr(-/-) and to a similar extent in aged Apoe(-/-)Ltbr(fl/fl)Tagln-cre mice. These data support the conclusion that the immune system employs ATLOs to organize aorta T cell homeostasis during aging and that VSMC-LTßRs participate in atherosclerosis protection via ATLOs.

Extracellular Matrix Remodeling in Vascular Disease: Defining Its Regulators and Pathological Influence.

Because of structural and cellular differences (ie, degrees of matrix abundance and cross-linking, mural cell density, and adventitia), large and medium-sized vessels, in comparison to capillaries, react in a unique manner to stimuli that induce vascular disease. A stereotypical vascular injury response is ECM (extracellular matrix) remodeling that occurs particularly in larger vessels in response to injurious stimuli, such as elevated angiotensin II, hyperlipidemia, hyperglycemia, genetic deficiencies, inflammatory cell infiltration, or exposure to proinflammatory mediators. Even with substantial and prolonged vascular damage, large- and medium-sized arteries, persist, but become modified by (1) changes in vascular wall cellularity; (2) modifications in the differentiation status of endothelial cells, vascular smooth muscle cells, or adventitial stem cells (each can become activated); (3) infiltration of the vascular wall by various leukocyte types; (4) increased exposure to critical growth factors and proinflammatory mediators; and (5) marked changes in the vascular ECM, that remodels from a homeostatic, prodifferentiation ECM environment to matrices that instead promote tissue reparative responses. This latter ECM presents previously hidden matricryptic sites that bind integrins to signal vascular cells and infiltrating leukocytes (in coordination with other mediators) to proliferate, invade, secrete ECM-degrading proteinases, and deposit injury-induced matrices (predisposing to vessel wall fibrosis). In contrast, in response to similar stimuli, capillaries can undergo regression responses (rarefaction). In summary, we have described the molecular events controlling ECM remodeling in major vascular diseases as well as the differential responses of arteries versus capillaries to key mediators inducing vascular injury.

Cystic adventitial disease of the common femoral artery: a case report and overview of the literature.

INTRODUCTION: Cystic adventitial disease (CAD) is an uncommon condition that affects arteries and veins. It can cause a rare type of non-atherosclerotic peripheral vessel disease. The most common vessel affected is the popliteal artery. The number of case reports on CAD of the femoral artery is growing. We present a case of a 62-year-old female presented with claudication of the left leg diagnosed with CAD of the left common femoral artery. The patient was treated surgically with cyst excision and vessel reconstruction with saphenous vein autograft patch plasty. After 8-months the cyste relapsed and she had new claudication complains. We decided to perform new surgery. Surgical treatment consisted of cyst resection by excision of the femoral bifurcation and saphenous vein autograft interposition reconstruction of the bifurcation. We also provide an update on the latest literature of surgical treatment of CAD of the ilio-femoral artery region. METHODS: Medline and EMBASE were used to collect articles on CAD of ilio-femoral artery. We included English written or translated case reports or series between 1987 and 2023. RESULTS: Twenty-nine patients out of 28 case reports were included. Most patients were male (59%). Claudication is the most common symptom (76%). Treatment consisted of cyst resection, cyst decompression, Endarterectomy, patch angioplasty and interposition graft using PTFE, Dacron, Great saphenous vein (GSV) or femoral vein autograft. Recurrence appeared in 4 cases (14%). CONCLUSION: In accordance to the literature and our experience we recommend complete vessel excision and saphenous vein (or PTFE) interposition bypass as treatment.

Isolation of vasa vasorum endothelial cells from pulmonary artery adventitia: Implementation to vascular biology research.

Isolated endothelial cells are valuable in vitro model for vascular research. At present, investigation of disease-relevant changes in vascular endothelium at the molecular level requires established endothelial cell cultures, preserving vascular bed-specific phenotypic characteristics. Vasa vasorum (VV) form a microvascular network around large blood vessels, in both the pulmonary and systemic circulations, that are critically important for maintaining the integrity and oxygen supply of the vascular wall. However, despite the pathophysiological significance of the VV, methods for the isolation and culture of vasa vasorum endothelial cells (VVEC) have not yet been reported. In our prior studies, we demonstrated the presence of hypoxia-induced angiogenic expansion of the VV in the pulmonary artery (PA) of neonatal calves; an observation which has been followed by a series of in vitro studies on isolated PA VVEC. Here we present a detailed protocol for reproducible isolation, purification, and culture of PA VVEC. We show these cells to express generic endothelial markers, (vWF, eNOS, VEGFR2, Tie1, and CD31), as well as progenitor markers (CD34 and CD133), bind lectin Lycopersicon Esculentum, and incorporate acetylated low-density lipoproteins labeled with acetylated LDL (DiI-Ac-LDL). qPCR analysis additionally revealed the expression of CD105, VCAM-1, ICAM-1, MCAM, and NCAM. Ultrastructural electron microscopy and immunofluorescence staining demonstrated that VVEC are morphologically characterized by a developed actin and microtubular cytoskeleton, mitochondrial network, abundant intracellular vacuolar/secretory system, and cell-surface filopodia. VVEC exhibit exponential growth in culture and can be mitogenically activated by multiple growth factors. Thus, our protocol provides the opportunity for VVEC isolation from the PA, and potentially from other large vessels, enabling advances in VV research.

High-Strength Injectable Hydrogel into Perivascular Interstitial Space Enhances Arterial Adventitial Stress.

Injectable hydrogels with strong mechanical properties have significant potential for biomedical applications, including the development of electronic skin, intelligent medical robots, as well as tissue engineering. In this study, we report on an injectable hydrogel with notable tensile strength and adhesion properties, achieved through cross-linking thiol-terminated four-arm poly (ethylene glycol) using silver-doped nano-hydroxyapatite, modified with dopamine. Subsequently, the hydrogel was injected in vivo through the perivascular interstitial space of rats. The hydrogel wrapped around the damaged abdominal aortic adventitia, which greatly increases the stress strength of the arterial adventitia. We found that the hydrogel was characterized by excellent biocompatibility, and it induced little immune response over a span of 21 days post-implantation. This simple and minimally invasive vascular protection strategy appears promising for the treatment of vascular diseases, such as abdominal aortic aneurysm (AAA).

Conductance Artery Wall Layers and Their Respective Roles in the Clearance Functions.

Evolutionary organization of the arterial wall into layers occurred concomitantly with the emergence of a highly muscularized, pressurized arterial system that facilitates outward hydraulic conductance and mass transport of soluble substances across the arterial wall. Although colliding circulating cells disperse potential energy within the arterial wall, the different layers counteract this effect: (1) the endothelium ensures a partial barrier function; (2) the media comprises smooth muscle cells capable of endocytosis/phagocytosis; (3) the outer adventitia and perivascular adipocytic tissue are the final receptacles of convected substances. While the endothelium forms a physical and a biochemical barrier, the medial layer is avascular, relying on the specific permeability properties of the endothelium for metabolic support. Different components of the media interact with convected molecules: medial smooth muscle cells take up numerous molecules via scavenger receptors and are capable of phagocytosis of macro/micro particles. The outer layers-the highly microvascularized innervated adventitia and perivascular adipose tissue-are also involved in the clearance functions of the media: the adventitia is the seat of immune response development, inward angiogenesis, macromolecular lymphatic drainage, and neuronal stimulation. Consequently, the clearance functions of the arterial wall are physiologically essential, but also may favor the development of arterial wall pathologies. This review describes how the walls of large conductance arteries have acquired physiological clearance functions, how this is determined by the attributes of the endothelial barrier, governed by endocytic and phagocytic capacities of smooth muscle cells, impacting adventitial functions, and the role of these clearance functions in arterial wall diseases.

Claudication due to adventitial cystic degeneration: A differential diagnosis of peripheral artery disease.

BACKGROUND: Cystic adventitial disease (CAD) is an important and rare non-atherosclerotic cause of intermittent claudication and critical limb ischemia. Since the first case of CAD involving the external iliac artery was described by Atkins and Key in 1947, approximately 300 additional cases have been reported. OBJECTIVES: The aim of this article is to report a rare vascular disorder, predominantly seen in young healthy men with minimal cardiovascular risk factors. METHODS: We report a rare case of cystic adventitial disease of a young policeman. To confirm the diagnosis, an ultrasonography and a conventional angiography were performed. The therapeutic approach was surgical first. RESULTS: The procedure was successful without any complication, and the patient was discharged to home 4 days after procedure. CONCLUSION: While CAD is rare, the diagnosis should be suspected in a young patient who presents with arterial insufficiency and no risk factors for atherosclerosis. Catheter angiography is the investigation of choice in the absence of multislice CT and good MRA. It seems that the treatment that assures the best long-term results is reconstructive arterial bypass surgery.

[Isolation, culture and validation of CD34+ vascular wall-resident stem cells from mice].

Vascular wall-resident stem cells (VW-SCs) play a critical role in maintaining normal vascular function and regulating vascular repair. Understanding the basic functional characteristics of the VW-SCs will facilitate the study of their regulation and potential therapeutic applications. The aim of this study was to establish a stable method for the isolation, culture, and validation of the CD34+ VW-SCs from mice, and to provide abundant and reliable cell sources for further study of the mechanisms involved in proliferation, migration and differentiation of the VW-SCs under various physiological and pathological conditions. The vascular wall cells of mouse aortic adventitia and mesenteric artery were obtained by the method of tissue block attachment and purified by magnetic microbead sorting and flow cytometry to obtain the CD34+ VW-SCs. Cell immunofluorescence staining was performed to detect the stem cell markers (CD34, Flk-1, c-kit, Sca-1), smooth muscle markers (SM22, SM MHC), endothelial marker (CD31), and intranuclear division proliferation-related protein (Ki-67). To verify the multipotency of the isolated CD34+ VW-SCs, endothelial differentiation medium EBM-2 and fibroblast differentiation medium FM-2 were used. After culture for 7 days and 3 days respectively, endothelial cell markers and fibroblast markers of the differentiated cells were evaluated by immunofluorescence staining and q-PCR. Furthermore, the intracellular Ca2+ release and extracellular Ca2+ entry signaling were evaluated by TILLvisION system in Fura-2/AM loaded cells. The results showed that: (1) High purity (more than 90%) CD34+ VW-SCs from aortic adventitia and mesenteric artery of mice were harvested by means of tissue block attachment method and magnetic microbead sorting; (2) CD34+ VW-SCs were able to differentiate into endothelial cells and fibroblasts in vitro; (3) Caffeine and ATP significantly activated intracellular Ca2+ release from endoplasmic reticulum of CD34+ VW-SCs. Store-operated Ca2+ entry (SOCE) was activated by using thapsigargin (TG) applied in Ca2+-free/Ca2+ reintroduction protocol. This study successfully established a stable and efficient method for isolation, culture and validation of the CD34+ VW-SCs from mice, which provides an ideal VW-SCs sources for the further study of cardiovascular diseases.

[Pathological changes in the nervous structures of the aortic wall tissue adjacent to an unstable atherosclerotic plaque]. / Patologicheskie izmeneniya nervnykh struktur v tkanyakh stenki aorty, prilezhashchikh k nestabil'noi ateroskleroticheskoi blyashke.

OBJECTIVE: To study of nerve structures in the aortic wall in atherosclerosis using a complex of immunohistochemical markers. MATERIAL AND METHODS: The objects of the study were excised fragments of the wall of the thoracic and abdominal aorta along with visually determined unstable atherosclerotic plaques. To study nerve structures on paraffin sections, immunohistochemical reactions were performed for the PGP 9.5 protein, tyrosine hydroxylase, and synaptophysin. RESULTS: It has been established that pronounced pathological changes are observed in the nervous structures of the aortic wall near unstable atherosclerotic plaques. Reactive, dystrophic, and severe degenerative changes in neurocytes, nerve fibers, and glial cells are described in the elements of the nervous apparatus of the adventitia (microganglia, nerve trunks, and nerve plexuses). It was found that only sympathetic neurons and their postganglionic fibers remain in the intramural ganglia, while the structures of the parasympathetic nervous apparatus undergo degeneration. Destruction of perivascular nerve plexuses and vasa vasorum in the adventitia, as well as degeneration of varicose axons of the main terminal synaptic plexus at the border of adventitia and superficial smooth muscle layer of the media were demonstrated. CONCLUSION: It is assumed that the presence of inflammatory infiltrates in the adventitia and intima, denervation and death of vasa vasorum can serve as factors determining the development of the atherosclerotic process.

Stromal cell-derived factor-1 exerts opposing roles through CXCR4 and CXCR7 in angiotensin II-induced adventitial remodeling.

Recent studies have emphasized the role of vascular adventitia inflammation and immune response in hypertension. It has been reported that stromal cell-derived factor-1 (SDF-1) plays various biological functions through its receptors C-X-C motif chemokine receptor 4 (CXCR4) and CXCR7 in tumor growth and tissue repair. However, it is unclear that whether SDF-1/CXCR4/CXCR7 axis is involved in hypertensive vascular remodeling. In the present study, the involvement of SDF-1/CXCR4/CXCR7 axis was evaluated with lentivirus-mediated shRNA of SDF-1 and CXCR7, CXCR4 antagonist AMD3100 and CXCR7 agonist VUF11207 in angiotensin II (AngII)-induced hypertensive mice and in cultured adventitial fibroblasts (AFs). Results showed that AngII infusion markedly increased SDF-1 expressed in vascular adventitia, but not in media and endothelium. Importantly, blockade of SDF-1/CXCR4 axis strikingly potentiated AngII-induced adventitial thickening and fibrosis, as indicated by enhanced collagen I deposition. In contrast, CXCR7 shRNA largely attenuated AngII-induced adventitial thickness and fibrosis, whereas CXCR7 activation with VUF11207 significantly potentiated AngII-induced adventitial thickening and fibrosis. In consistent with these in vivo study, CXCR4 inhibition with AMD3100 and CXCR7 activation with VUF11207 aggravated AngII-induced inflammation, proliferation and migration in cultured AFs. In summary, these results suggested that SDF-1 exerted opposing effects through CXCR4 and CXCR7 in AngII-induced vascular adventitial remodeling.

FABP3 overexpression promotes vascular fibrosis in Takayasu's arteritis by enhancing fatty acid oxidation in aorta adventitial fibroblasts.

OBJECTIVE: To identify the role of fatty acid binding protein 3 (FABP3) in vascular fibrosis in Takayasu's arteritis (TAK) and to explore the underlying molecular mechanism. METHODS: The expression of FABP3 and extracellular matrix proteins (ECMs) were detected in aorta tissues from TAK patients (n = 12) and healthy controls (n = 8) by immunohistochemistry. The concentration of serum proteins was determined by ELISA. CCK8 and Ki67 staining were used to measure aorta adventitial fibroblast (AAF) proliferation. Widely targeted lipidomic profiling was used to screen for associated metabolic pathways. Changes in ECMs and fatty acid oxidation (FAO)-related enzymes were determined by RT-qPCR and Western blot. The interactions between FABP3 and these enzymes were explored with a co-immunoprecipitation (Co-IP) assay. RESULTS: The expression of FABP3 was increased in the thickened adventitia of TAK patients and was positively correlated with the serum expression of ECMs. FABP3 knockdown inhibited AAF proliferation and ECM production, whereas FABP3 overexpression enhanced these processes. Further analysis revealed that FABP3 upregulation promoted carnitine palmitoyltransferase 1A and carnitine/acylcarnitine carrier protein (CACT) expression, two key enzymes in FAO, as well as adenosine triphosphate (ATP) levels. FABP3 and CACT were co-localized in the adventitia and bound to each other in AAFs. Etomoxir reversed the enhanced FAO, ATP production, AAF proliferation and ECM production mediated by FABP3 upregulation. Treatment with 60 g/day curcumin granules for 3 months reduced the level of serum FABP3. Curcumin also inhibited vascular fibrosis by reducing FABP3-enhanced FAO in AAFs. CONCLUSION: Elevated FABP3 expression accelerated vascular fibrosis in TAK, which was likely mediated by promoting FAO in AAFs.

Gal-1 (Galectin-1) Upregulation Contributes to Abdominal Aortic Aneurysm Progression by Enhancing Vascular Inflammation.

OBJECTIVE: Abdominal aortic aneurysm (AAA) is a vascular degenerative disease causing sudden rupture of aorta and significant mortality in elders. Nevertheless, no prognostic and therapeutic target is available for disease management. Gal-1 (galectin-1) is a ß-galactoside-binding lectin constitutively expressed in vasculature with roles in maintaining vascular homeostasis. This study aims to investigate the potential involvement of Gal-1 in AAA progression. Approach and Results: Gal-1 was significantly elevated in circulation and aortic tissues of Ang II (angiotensin II)-infused apoE-deficient mice developing AAA. Gal-1 deficiency reduced incidence and severity of AAA with lower expression of aortic MMPs (matrix metalloproteases) and proinflammatory cytokines. TNFα (tumor necrosis factor alpha) induced Gal-1 expression in cultured vascular smooth muscle cells and adventitial fibroblasts. Gal-1 deletion enhanced TNFα-induced MMP9 expression in fibroblasts but not vascular smooth muscle cells. Cysteinyl-labeling assay demonstrated that aortic Gal-1 exhibited susceptibility to oxidation in vivo. Recombinant oxidized Gal-1 induced expression of MMP9 and inflammatory cytokines to various extents in macrophages, vascular smooth muscle cells, and fibroblasts through activation of MAP (mitogen-activated protein) kinase signaling. Clinically, serum MMP9 level was significantly higher in both patients with AAA and coronary artery disease than in control subjects, whereas serum Gal-1 level was elevated in patients with AAA but not coronary artery disease when compared with controls. CONCLUSIONS: Gal-1 is highly induced and contributes to AAA by enhancing matrix degradation activity and inflammatory responses in experimental model. The pathological link between Gal-1 and AAA is also observed in human patients. These findings support the potential of Gal-1 as a disease biomarker and therapeutic target of AAA.

Mechanisms of abdominal aortic aneurysm progression: A review.

Abdominal aortic aneurysm (AAA) is a common disease associated with significant cardiovascular morbidity and mortality. Up to now, there is still controversy on the choice of treatment method of AAA. Even so, the mechanisms of AAA progression are poorly defined, making targeting new therapies problematic. Current evidence favors an interaction of the hemodynamic microenvironment with local and systemic immune responses. In this review, we aim to provide an update of mechanisms in AAA progression, involving hemodynamics, perivascular adipose tissue, adventitial fibroblasts, vasa vasorum remodeling, intraluminal thrombus, and distribution of macrophage subtypes.

Renal Interstitial Fibrosis Is Reduced in High-Fat Diet-Induced Obese Pigs following Renal Denervation from the Intima and Adventitia of the Renal Artery.

BACKGROUND: This study aims to compare whether 2 different routes of renal denervation (RDN) from the intima and adventitia of the renal artery can reduce renal fibrosis in a pig model of hypertension induced by a high-fat diet and to explore possible molecular mechanisms. METHODS: Twenty-four Bama miniature pigs were randomly divided into a control group (normal diet, n = 6) or a hypertension model group (high-fat diet, n = 18). The model group was randomly divided into the intima-RDN group (n = 6), the adventitia-RDN group (n = 6), or the renal arteriography-only group (sham group, n = 6). All animals were fed separately. The model group was fed a high-fat diet after the operation, and the control group was fed conventionally for 6 months. After 6 months, renal artery angiography was performed again to observe the condition of the renal arteries, after which all animals were euthanized. The blood pressure and blood biochemical results of each group were evaluated 6 months after the operation; kidney tissue morphology and collagen fiber content were examined by hematoxylin-eosin staining and Masson staining; superoxide dismutase activity and the malondialdehyde content of kidney tissue were assessed by a biochemical enzyme method; the protein expression level of transforming growth factor-ß 1 (TGF-ß1), α-smooth muscle actin (α-SMA), and Smad3 was assessed by Western blot, and electron microscopy was used to examine changes in the kidney microstructure. RESULTS: After 6 months of a high-fat diet, the blood lipid levels of the model group were significantly higher compared to baseline and to that of the control group during the same period (all showed p < 0.05); the blood lipid levels of the control group did not change significantly from baseline (p > 0.05). The degree of glomerular damage caused by hyperlipidemia in the intima-RDN group and the adventitia-RDN group was significantly lower than that of the sham and control groups, and the renal fibrosis area percentage was also significantly lower (p < 0.05). Electron microscopy showed that both the intima-RDN group and the adventitia-RDN group had a more even distribution of chromosomes and less mitochondrial swelling compared with the sham group. CONCLUSION: RDN from the adventitia of the renal artery and RDN from the intima of the renal artery have the similar advantages of delaying high-fat-induced renal fibrosis. The antifibrotic effect of RDN may be related to inhibition of the TGF-ß1/Smad3 pathway.

Updates in aortic wall pathology.

Several studies have investigated the pathogenesis of aortic wall abnormalities such as aortic dissection or aneurysm; however, the comprehensive pathological in situ event involved in the development of the disease is not understood well. The vasa vasorum form a network of capillaries or venules around the adventitia and outer media, which play an important role in the aortic wall structure and function. Impairment of their function may induce tissue hypoxia, impede the transfer of cellular nutrients, and cause aortic medial degeneration, which is considered the major predisposing factor to this aortic wall pathology. This review updates our understanding of the pathological changes in the aortic media and vasa vasorum of patients with aortic dissection and aortic aneurysm.

Homocysteine promotes migration of adventitial fibroblasts via angiotensin II type 1 receptor activation to aggravate atherosclerosis.

This study clarified the effect of homocysteine on adventitial fibroblasts (AFs) and its relationship with angiotensin II type 1 receptor (AT1R). Hyperhomocysteinemia aggravated the plaque area and increased the expression of IL-6, MCP-1, and macrophage infiltration in the plaque and adventitia of the aorta, whereas telmisartan improved this effect. Hyperhomocysteinemia induced the occurrence of the AFs marker protein ER-TR7 in the plaque and entire layer of the aorta, whereas telmisartan improved these effects, indicating that homocysteine induced AFs migration and that AT1R mediated this process. The migration experiments of AFs also reached the same conclusion. Homocysteine increased the phosphorylation levels of PKC and ERK1/2 in the AFs and HEK293A cells transfected with the AT1R plasmid, whereas telmisartan inhibited this effect, indicating that homocysteine activated AT1R intracellular signaling pathway. Homocysteine also increased the AFs At1R expression. Conclusion, homocysteine promoted adventitial inflammation, induced AFs migration, and aggravated atherosclerosis by activating AT1R.

A Deep Learning-based Method to Extract Lumen and Media-Adventitia in Intravascular Ultrasound Images.

Intravascular ultrasound (IVUS) imaging allows direct visualization of the coronary vessel wall and is suitable for assessing atherosclerosis and the degree of stenosis. Accurate segmentation and lumen and median-adventitia (MA) measurements from IVUS are essential for such a successful clinical evaluation. However, current automated segmentation by commercial software relies on manual corrections, which is time-consuming and user-dependent. We aim to develop a deep learning-based method using an encoder-decoder deep architecture to automatically and accurately extract both lumen and MA border. Inspired by the dual-path design of the state-of-the-art model IVUS-Net, our method named IVUS-U-Net++ achieved an extension of the U-Net++ model. More specifically, a feature pyramid network was added to the U-Net++ model, enabling the utilization of feature maps at different scales. Following the segmentation, the Pearson correlation and Bland-Altman analyses were performed to evaluate the correlations of 12 clinical parameters measured from our segmentation results and the ground truth. A dataset with 1746 IVUS images from 18 patients was used for training and testing. Our segmentation model at the patient level achieved a Jaccard measure (JM) of 0.9080 ± 0.0321 and a Hausdorff distance (HD) of 0.1484 ± 0.1584 mm for the lumen border; it achieved a JM of 0.9199 ± 0.0370 and an HD of 0.1781 ± 0.1906 mm for the MA border. The 12 clinical parameters measured from our segmentation results agreed well with those from the ground truth (all p-values are smaller than .01). Our proposed method shows great promise for its clinical use in IVUS segmentation.

Heparin-free adventitia pulmonary oxygenation in the treatment of trauma complicated with severe pulmonary infection: a case report.

The application of Venovenous (VV) extracorporeal membrane oxygenation (ECMO) in trauma and patients with severe bleeding tendency has been controversial. However, VV ECMO without anticoagulation contributes to reducing the risk of bleeding during ECMO maintenance. VV ECMO serves critical roles in therapy of patients with severe pulmonary infection and failure in conventional therapy. The common peripheral catheterization approach for VV ECMO is femoral vein-internal jugular vein catheterization, and bilateral femoral vein catheterization can also achieve the purpose of respiratory support for patients with limited cervical catheterization. In this case report, we described a patient with post-traumatic cervical spinal cord injury and severe pulmonary infection who was successfully treated with heparin-free intravenous ECMO.