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Frontiers in Physiology 2024Redox processes can modulate vascular pathophysiology. The endoplasmic reticulum redox chaperone protein disulfide isomerase A1 (PDIA1) is overexpressed during vascular...
Redox processes can modulate vascular pathophysiology. The endoplasmic reticulum redox chaperone protein disulfide isomerase A1 (PDIA1) is overexpressed during vascular proliferative diseases, regulating thrombus formation, endoplasmic reticulum stress adaptation, and structural remodeling. However, both protective and deleterious vascular effects have been reported for PDIA1, depending on the cell type and underlying vascular condition. Further understanding of this question is hampered by the poorly studied mechanisms underlying PDIA1 expression regulation. Here, we showed that PDIA1 mRNA and protein levels were upregulated (average 5-fold) in the intima and media/adventitia following partial carotid ligation (PCL). Our search identified that miR-204-5p and miR-211-5p (miR-204/211), two broadly conserved miRNAs, share PDIA1 as a potential target. MiR-204/211 was downregulated in vascular layers following PCL. In isolated endothelial cells, gain-of-function experiments of miR-204 with miR mimic decreased PDIA1 mRNA while having negligible effects on markers of endothelial activation/stress response. Similar effects were observed in vascular smooth muscle cells (VSMCs). Furthermore, PDIA1 downregulation by miR-204 decreased levels of the VSMC contractile differentiation markers. In addition, PDIA1 overexpression prevented VSMC dedifferentiation by miR-204. Collectively, we report a new mechanism for PDIA1 regulation through miR-204 and identify its relevance in a model of vascular disease playing a role in VSMC differentiation. This mechanism may be regulated in distinct stages of atherosclerosis and provide a potential therapeutic target.
PubMed: 38638277
DOI: 10.3389/fphys.2024.1327794 -
Cardiovascular Pathology : the Official... 2024Exertional dyspnea has been documented in US military personnel after deployment to Iraq and Afghanistan. We studied whether continued exertional dyspnea in this patient...
Exertional dyspnea has been documented in US military personnel after deployment to Iraq and Afghanistan. We studied whether continued exertional dyspnea in this patient population is associated with pulmonary vascular disease (PVD). We performed detailed histomorphometry of pulmonary vasculature in 52 Veterans with biopsy-proven post-deployment respiratory syndrome (PDRS) and then recruited five of these same Veterans with continued exertional dyspnea to undergo a follow-up clinical evaluation, including symptom questionnaire, pulmonary function testing, surface echocardiography, and right heart catheterization (RHC). Morphometric evaluation of pulmonary arteries showed significantly increased intima and media thicknesses, along with collagen deposition (fibrosis), in Veterans with PDRS compared to non-diseased (ND) controls. In addition, pulmonary veins in PDRS showed increased intima and adventitia thicknesses with prominent collagen deposition compared to controls. Of the five Veterans involved in our clinical follow-up study, three had borderline or overt right ventricle (RV) enlargement by echocardiography and evidence of pulmonary hypertension (PH) on RHC. Together, our studies suggest that PVD with predominant venular fibrosis is common in PDRS and development of PH may explain exertional dyspnea and exercise limitation in some Veterans with PDRS.
Topics: Humans; Male; Pulmonary Artery; Adult; Hypertension, Pulmonary; Middle Aged; Female; Afghan Campaign 2001-; Iraq War, 2003-2011; Pulmonary Veins; Dyspnea; Veterans; Case-Control Studies; Veterans Health; Biopsy; Fibrosis
PubMed: 38604505
DOI: 10.1016/j.carpath.2024.107640 -
Cardiovascular Research May 2024The interleukin-1 receptor accessory protein (IL1RAP) is a co-receptor required for signalling through the IL-1, IL-33, and IL-36 receptors. Using a novel...
AIMS
The interleukin-1 receptor accessory protein (IL1RAP) is a co-receptor required for signalling through the IL-1, IL-33, and IL-36 receptors. Using a novel anti-IL1RAP-blocking antibody, we investigated the role of IL1RAP in atherosclerosis.
METHODS AND RESULTS
Single-cell RNA sequencing data from human atherosclerotic plaques revealed the expression of IL1RAP and several IL1RAP-related cytokines and receptors, including IL1B and IL33. Histological analysis showed the presence of IL1RAP in both the plaque and adventitia, and flow cytometry of murine atherosclerotic aortas revealed IL1RAP expression on plaque leucocytes, including neutrophils and macrophages. High-cholesterol diet fed apolipoprotein E-deficient (Apoe-/-) mice were treated with a novel non-depleting IL1RAP-blocking antibody or isotype control for the last 6 weeks of diet. IL1RAP blockade in mice resulted in a 20% reduction in subvalvular plaque size and limited the accumulation of neutrophils and monocytes/macrophages in plaques and of T cells in adventitia, compared with control mice. Indicative of reduced plaque inflammation, the expression of several genes related to leucocyte recruitment, including Cxcl1 and Cxcl2, was reduced in brachiocephalic arteries of anti-IL1RAP-treated mice, and the expression of these chemokines in human plaques was mainly restricted to CD68+ myeloid cells. Furthermore, in vitro studies demonstrated that IL-1, IL-33, and IL-36 induced CXCL1 release from both macrophages and fibroblasts, which could be mitigated by IL1RAP blockade.
CONCLUSION
Limiting IL1RAP-dependent cytokine signalling pathways in atherosclerotic mice reduces plaque burden and plaque inflammation, potentially by limiting plaque chemokine production.
Topics: Animals; Female; Humans; Male; Mice; Anti-Inflammatory Agents; Atherosclerosis; Disease Models, Animal; Inflammation; Interleukin-1 Receptor Accessory Protein; Macrophages; Mice, Inbred C57BL; Mice, Knockout, ApoE; Plaque, Atherosclerotic; Signal Transduction
PubMed: 38563353
DOI: 10.1093/cvr/cvae046 -
JACC. Basic To Translational Science Mar 2024Neutrophil extracellular traps (NETs) are implicated in the pathogenesis of abdominal aortic aneurysm (AAA), located in adventitia and intraluminal thrombus. We...
Neutrophil extracellular traps (NETs) are implicated in the pathogenesis of abdominal aortic aneurysm (AAA), located in adventitia and intraluminal thrombus. We compared the therapeutic potential of targeting upstream or downstream effector molecules of NET formation in 2 murine AAA models based on angiotensin II or peri-adventitial elastase application. In both models, NETs were detected in formed aneurysms at treatment start. Although NET inhibitors failed in the elastase model, they prevented progression of angiotensin II-induced aneurysms with thrombus, which resembles established human disease (including thrombus development). Blockade of upstream NET mediators was more effective than interference with downstream NET molecules.
PubMed: 38559632
DOI: 10.1016/j.jacbts.2023.11.003 -
Biomedicines Feb 2024Despite advancements in coronary artery bypass grafting (CABG), the optimal choice of graft material remains a subject of investigation. This study aimed to...
The Controversy of Using Insufficient Great Saphenous Veins in Coronary Artery Bypass Grafting: A Comparative Morphological Analysis of Healthy and Insufficient Veins Related to the Possibility of Using Them as a Graft.
BACKGROUND
Despite advancements in coronary artery bypass grafting (CABG), the optimal choice of graft material remains a subject of investigation. This study aimed to comprehensively analyze the morphological characteristics of varicose veins, exploring their potential utilization in CABG compared to healthy veins.
METHODS
The study included 178 patients, categorized into two groups based on healthy and varicose veins. Morphological parameters, including maximum venous diameter, wall thickness, and specific changes in tunica intima (TI), tunica media (TM), and tunica adventitia (TA), were analyzed through microscopic evaluation.
RESULTS
Varicose veins exhibited a significantly larger maximum venous diameter ( = 0.0001) and increased wall thickness ( = 0.0001) compared to healthy veins. Although varicose veins showed thickening in TI and TM, the differences were not statistically significant. Notably, disorganized smooth muscle bundles were more prevalent in varicose veins ( = 0.001), suggesting potential wall weakness. The absence of vasa vasorum in TA was significantly higher in varicose veins ( = 0.050), influencing vascularization considerations.
CONCLUSIONS
The comparative morphological microscopic analysis of the specimens of healthy and varicose veins reveals significant differences between the groups, which make the conclusion of this study to plead for avoiding the use of varicose veins as a graft.
PubMed: 38540090
DOI: 10.3390/biomedicines12030476 -
Brain Sciences Mar 2024To evaluate the efficacy of perivascular sympathectomy in managing adventitia layer-related long-segment tubular stenosis of cervical segment (C1) internal carotid...
Adventitia Layer-Focused Microsurgical Flow Reconstruction for Long-Segment Tubular Stenosis of the Cervical Segment (C1) Internal Carotid Artery: Clinical Valuable Experience in 20 Cases.
To evaluate the efficacy of perivascular sympathectomy in managing adventitia layer-related long-segment tubular stenosis of cervical segment (C1) internal carotid arteries (ICAs) in a cohort where conventional medical and endovascular interventions were not viable options, we retrospectively analyzed 20 patients (8 males, 12 females, aged 41-63 years) who underwent perivascular sympathectomy for long-segment (>5 cm) tubular cervical ICA stenosis (non-atherosclerotic, non-intima related, and nondolichoarteriopathic) between 2017 and 2023. The procedure aimed to alleviate symptoms such as hemiparesis, pulsatile tinnitus, and migraines associated with transient ischemic attacks (TIAs). Preoperative and postoperative symptoms were assessed, and patient follow-up was conducted by MR angiography and perfusion studies. Postoperatively, 10 out of 11 migraine sufferers (90.9%) reported complete cessation of symptoms, while one patient (9.09%) experienced reduction in frequency and intensity. In cases of tinnitus, six out of nine patients (66.6%) reported complete resolution, two (22.2%) had reduced symptoms, and one (11.1%) saw no change. Regarding motor function, all 12 patients (100%) with initial hemiparesis (30-40% loss of motor function) showed complete recovery postoperatively. There was no TIA attack among the patients after the procedure in the mean two-year follow-up. Perivascular sympathectomy has shown promising results in alleviating symptoms and preventing recurrent cerebrovascular events in long-segment tubular stenosis of cervical ICAs.
PubMed: 38539676
DOI: 10.3390/brainsci14030289 -
IScience Apr 2024Converging studies showed interstitial fluid (ISF) adjacent to blood vessels flows in adventitia along vasculature into heart and lungs. We aim to reveal circulatory...
Converging studies showed interstitial fluid (ISF) adjacent to blood vessels flows in adventitia along vasculature into heart and lungs. We aim to reveal circulatory pathways and regulatory mechanism of such adventitial ISF flow in rat model. By MRI, real-time fluorescent imaging, micro-CT, and histological analysis, ISF was found to flow in adventitial matrix surrounded by fascia and along systemic vessels into heart, then flow into lungs via pulmonary arteries and back to heart via pulmonary veins, which was neither perivascular tissues nor blood or lymphatic vessels. Under physiological conditions, speckle-like adventitial ISF flow rate was positively correlated with heart rate, increased when holding breath, became pulsative during heavy breathing. During cardiac or respiratory cycle, each dilation or contraction of heart or lungs can generate to-and-fro adventitial ISF flow along femoral veins. Discovered regulatory mechanisms of adventitial ISF flow along vasculature by heart and lungs will revolutionize understanding of cardiovascular system.
PubMed: 38532885
DOI: 10.1016/j.isci.2024.109407 -
International Journal of Surgery Case... Apr 2024Cystic adventitial disease (CAD) is a rare vascular disorder marked by occlusion stemming from the development of a cystic mass within the outer (subadventitial) layer,...
INTRODUCTION AND IMPORTANCE
Cystic adventitial disease (CAD) is a rare vascular disorder marked by occlusion stemming from the development of a cystic mass within the outer (subadventitial) layer, with a predominant impact on the popliteal artery. The significance of the case presented herein lies in shedding light on a distinct clinical manifestation involving a 40-year-old man who exhibited sporadic calf claudication during ambulation. This instance contributes to the broader understanding of CAD and its diverse clinical presentations, emphasizing the need for further exploration and awareness within the medical community.
CASE PRESENTATION
A 40-year-old man, with no significant past medical history, was referred to the cardiovascular department for the evaluation of a new onset of left calf pain persisting over the past three months. An arterial lower limb Doppler ultrasound was performed, revealing a focal hypoechoic image around the popliteal artery with a regular arterial wall, indicative of extrinsic compression. This resulted in significant stenosis of the popliteal artery during plantar flexion of the foot. The diagnosis of CAD of the left popliteal artery was established after limb computed tomography angiography, and a complete resection of the cyst was scheduled. The postoperative course was uneventful, with the patient experiencing relief from left calf claudication.
CLINICAL DISCUSSION
CAD is an uncommon vascular anomaly, representing merely 0.1 % of all vascular conditions. This condition predominantly afflicts men aged between 40 and 50 years old. The etiology of CAD remains a subject of debate, with pathological findings typically involving intramural cysts containing gelatinous material between the media and the adventitia. Surgical intervention becomes necessary when symptoms arise.
CONCLUSION
CAD of the popliteal artery, though rare, is a significant contributor to peripheral vascular insufficiency in young patients without typical atherosclerotic risk factors.
PubMed: 38522307
DOI: 10.1016/j.ijscr.2024.109541 -
Clinical Case Reports Mar 2024The presence of multiple pseudoaneurysms in a patient should prompt investigations for the underlying etiologies including autoimmune and immunosuppressive disease...
KEY CLINICAL MESSAGE
The presence of multiple pseudoaneurysms in a patient should prompt investigations for the underlying etiologies including autoimmune and immunosuppressive disease processes. Treatment options include open repair and endovascular stenting.
ABSTRACT
Pseudoaneurysms (also known as false aneurysms) are atypical dilatations or outpouchings from a vessel which are not always contained by the three layers of a normal vessel wall, namely the intima, media, and adventitia. These are distinct from a true aneurysm which has a wall comprising all three layers. The underlying etiology for both true aneurysms and pseudoaneurysm can vary. We present the rare case of bilateral superficial femoral artery pseudoaneurysms, of unknown etiology and a concurrent posterior tibial artery saccular aneurysm in a patient with Human Immunodeficiency Virus (HIV) infection and multiple comorbidities. This was managed using a combination of endovascular covered stent grafts and open surgical repair technique. The patient is doing well on follow-up a year later with no post-operative infections. A literature review of the existing reports of superficial femoral artery pseudoaneurysms and posterior tibial artery aneurysms and their management is also reported.
PubMed: 38515996
DOI: 10.1002/ccr3.8686 -
International Angiology : a Journal of... Apr 2024Sclerotherapy is a cornerstone of the treatment of chronic venous disease, despite some technical aspects (e.g., sclerosant liquid agent concentration [SLAC] and contact...
Empty vein ablation (EVA) technique: an in-vivo animal model to assess the effects of sclerosing agent concentration and wall contact time on intima and media tunicae structure.
BACKGROUND
Sclerotherapy is a cornerstone of the treatment of chronic venous disease, despite some technical aspects (e.g., sclerosant liquid agent concentration [SLAC] and contact time between sclerosant agent and vein wall [ctSA/VW]) to maximize outcomes remain an unsolved problem and a source of debate. An innovative three-balloon catheter has been developed to allow sclerotherapy in empty vein conditions (Empty Vein Ablation technique, EVA), revolutionizing the definition of SLAC and ctSA/VW. Aim of this experimental study is to analyze EVA effects on intima and media vessel tunicae using different SLAC and ctSA/VW in an in-vivo animal model.
METHODS
Two adult sheep were treated by EVA using jugular and common iliac vein axes (eight vein segments). Different SLAC (polidocanol 0.5% or 1%) and different ctSA/VW (3 or 5 minutes) were combined for testing residual circumferential intima percentage and media thickness after EVA.
RESULTS
Intact circumferential residual intima after the treatment was 21.3±4.9%, 18.2±7.4%, 15.7±2.4% and 8.9±2.0% using 0.5% (3 min), 0.5% (5 min), 1% (3 min) and 1% (5 min), respectively (R=0.945; control sample: 97.6%). Media thickness after the treatment was 121.6±35.3 µm, 110.9±7.8 µm, 96.1±30.4 µm and 79.1±34.1 µm using 0.5% (3 min), 0.5% (5 min), 1% (3 min) and 1% (5 min), respectively (R=0.990; control sample 125.7 µm). No significant modifications were detected analyzing the adventitia in all samples.
CONCLUSIONS
EVA proved to be effective in venous wall destruction even with a very low SLAC and ctSA/VW (0.5% in 3 minutes), in quite large caliber veins. Direct comparisons with foam/liquid sclerotherapy should be done to confirm therapeutic effectiveness of these results, despite EVA has provided a maximized and controlled SA/VW contact time and ratio.
Topics: Animals; Sclerosing Solutions; Sclerotherapy; Tunica Intima; Polidocanol; Tunica Media; Sheep; Iliac Vein; Jugular Veins; Time Factors; Ablation Techniques; Models, Animal; Disease Models, Animal
PubMed: 38512703
DOI: 10.23736/S0392-9590.24.05147-2