Vascular Injury Research Articles

Short Sleep Duration and Hypertension: A Double Hit for the Brain.

Short sleep duration has been associated with an increased risk of cognitive impairment and dementia. Short sleep is associated with elevated blood pressure, yet the combined insult of short sleep and hypertension on brain health remains unclear. We assessed whether the association of sleep duration with cognition and vascular brain injury was moderated by hypertensive status. A total of 682 dementia-free participants (mean age, 62±9 years; 53% women) from the Framingham Heart Study completed assessments of cognition, office blood pressure, and self-reported habitual and polysomnography-derived sleep duration; 637 underwent brain magnetic resonance imaging. Linear regressions were performed to assess effect modification by hypertensive status on total sleep time (coded in hours) and cognitive and magnetic resonance imaging outcomes. There was a significant interaction between sleep duration and hypertensive status when predicting executive function/processing speed (Trail Making B-A) and white matter hyperintensities. When results were stratified by hypertensive status, longer sleep duration was associated with better executive functioning/processing speed scores in the hypertensive group (meaning that shorter sleep duration was associated with poorer executive function/processing speed scores) (self-report sleep: β=0.041 [95% CI, 0.012-0.069], P=0.005; polysomnography sleep: β=0.045 [95% CI, 0.002-0.087], P=0.038), but no association was observed for the normotensive group. Similarly, shorter subjective sleep duration was associated with higher white matter hyperintensity burden in the hypertensive group (β=-0.115 [95% CI, -0.227 to -0.004], P=0.042), but not in the normotensive group. In individuals with hypertension, shorter sleep duration was associated with worse cognitive performance and greater brain injury.

NAT10 promotes vascular remodelling via mRNA ac4C acetylation.

Vascular smooth muscle cell (VSMC) phenotype switching is a pathological hallmark in various cardiovascular diseases. N4-acetylcytidine (ac4C) catalyzed by N-acetyltransferase 10 (NAT10) is well conserved in the enzymatic modification of ribonucleic acid (RNA). NAT10-mediated ac4C acetylation is involved in various physiological and pathological processes, including cardiac remodelling. However, the biological functions and underlying regulatory mechanisms of mRNA ac4C modifications in vascular diseases remain elusive. By combining in-vitro and in-vivo vascular injury models, NAT10 was identified as a crucial protein involved in the promotion of post-injury neointima formation, as well as VSMC phenotype switching. The potential mechanisms of NAT10 in the vascular neointima formation were clarified by RNA sequence (RNA-seq), acetylated mRNA immunoprecipitation sequence (acRIP-seq), and RNA binding protein immunoprecipitation sequence (RIP-seq). NAT10 and ac4C modifications were upregulated in injured human and rodent arteries. Deletion of NAT10 in VSMCs effectively reduced post-injury neointima formation and VSMC phenotype switching. Further RNA-seq, RIP-seq, and acRIP-seq revealed that NAT10, by its ac4C modification, directly interacts with genes, including integrin-β1 (ITGB1) and collagen type I alpha 2 chain (Col1a2) mRNAs. Taking ITGB1 as one example, it showed that NAT10-mediated ac4C consequently increased ITGB1 mRNA stability and its downstream focal adhesion kinase (FAK) signaling, directly influencing the proliferation of VSMCs and vascular remodelling. The regulation of NAT10 on the VSMC phenotype is of translational significance because the administration of Remodelin, a NAT10 inhibitor, effectively prevents neointima formation by suppressing VSMC proliferation and downregulating ITGB1 expression and deactivating its FAK signaling. This study reveals that NAT10 promotes vascular remodelling via mRNA ac4C acetylation, which may be a promising therapeutic target against vascular remodelling.

NIK Is a Mediator of Inflammation and Intimal Hyperplasia in Endothelial Denudation-Induced Vascular Injury.

Neointimal hyperplasia is the main cause of vascular graft failure in the medium term. NFκB is a key mediator of inflammation that is activated during neointimal hyperplasia following endothelial injury. However, the molecular mechanisms involved in NFκB activation are poorly understood. NFκB may be activated through canonical (transient) and non-canonical (persistent) pathways. NFκB-inducing kinase (NIK, MAP3K14) is the upstream kinase of the non-canonical pathway. We have now explored the impact of NIK deficiency on neointimal hyperplasia following guidewire-induced endothelial cell injury and on local inflammation by comparing NIK activity-deficient alymphoplasia mice (NIKaly/aly) with control wild-type (NIK+/+) mice. Guidewire-induced endothelial cell injury caused neointimal hyperplasia and luminal stenosis and upregulated the local expression of NIK and the NFκB target chemokines monocyte chemoattractant protein-1 (MCP-1/CCL2) and chemokine ligand 5 (RANTES/CCL5). Immunohistochemistry disclosed the infiltration of the media and intima by F4/80 positive macrophages. The intima/media ratio and percentage of stenosis were milder in the NIKaly/aly than in the NIK+/+ mice. Additionally, the gene expression for MCP-1 and RANTES was lower and F4/80+ cell infiltration was milder in the NIKaly/aly than in the NIK+/+ mice. Finally, circulating MCP-1 levels were lower in the NIKaly/aly than in the NIK+/+ mice, reflecting milder systemic inflammation. In conclusion, NIK is a driver of vascular wall inflammation and stenosis following guidewire-induced endothelial cell injury. NIK targeting may be a novel therapeutic approach to limit arterial stenosis following endothelial cell injury.

The Basic Principles of Pathophysiology of Venous Thrombosis.

The past few decades have brought tremendous insight into the molecular and pathophysiological mechanisms responsible for thrombus generation. For a clinician, it is usually sufficient to explain the incident of deep vein thrombosis (DVT) with provoking factors such as trauma with vascular injury, immobilization, hormonal factors, or inherited or acquired coagulation defects. About half of DVTs are, however, lacking such triggers and are called unprovoked. Venous stasis and hypoxia at the valve sinus level may start a chain of reactions. The concept of immunothrombosis has added a new dimension to the old etiological triad of venous stasis, vessel wall injury, and changes in blood components. This is particularly important in COVID-19, where hyperinflammation, cytokines, and neutrophil extracellular traps are associated with the formation of microthrombi in the lungs. To better understand the mechanisms behind DVT and reach beyond the above-mentioned simplifications, animal models and clinical epidemiological studies have brought insight into the complex interplay between leukocytes, platelets, endothelium, cytokines, complements, and coagulation factors and inhibitors. These pathways and the interplay will be reviewed here, as well as the roles of cancer, anticancer drugs, and congenital thrombophilic defects on the molecular level in hypercoagulability and venous thromboembolism.

Radiation-Induced Macrovessel/Microvessel Disease.

Radiation therapy (RT) is a cornerstone in cancer treatment (used in 50% of cases), yet challenges persist because damage to normal tissue through direct impact of radiation or bystander effects is inevitable. Injury of macrovessels by RT manifests as obstructive disease, which is akin to atherosclerotic disease. Historically observed in coronary arteries of patients treated for breast cancer and lymphoma, it also affects patients receiving contemporary therapy for lung and chest cancers. Moreover, radiation at various sites can lead to peripheral vascular disease. An aspect of radiation-induced injury that has received little attention is microvascular injury, which typically results from damage to the endothelium and is considered the primary driver of RT-induced toxicity in the skin, kidney, and brain. This review delves into the clinical manifestations of RT-induced vascular disease, signaling pathways, cellular targets affected by radiation injury, and preclinical models of RT-induced vascular injury. The goal is to inspire the development of innovative strategies to prevent RT-related cardiovascular disease.

Analysis of the efficacy of triple-channel minimally invasive knee arthroscopy in treating popliteal cysts in children

BackgroundThis study aimed to investigate a technique for treating pediatric popliteal cysts with a triple-channel knee arthroscopic approach, hypothesizing that this technique exhibits favorable clinical outcomes with reduced recurrence rates.MethodsA retrospective analysis was conducted on the clinical data of 14 patients with symptomatic pediatric popliteal cysts admitted to the joint surgery center using an arthroscopic minimally invasive technique from December 2017 to December 2020. Arthroscopy was employed for adequate enlargement of the posterior medial flap opening between the cyst and the joint cavity and to completely resect the cyst wall. The popliteal cyst recurrence was assessed through Magnetic Resonance Imaging(MRI) at 3 and 12 months post-surgery, and the Rauschning and Lindgren scores were recorded to evaluate the clinical prognosis.ResultsA total of 14 children completed the follow-up, including 8 boys and 6 girls, with a mean age of 9.9 ± 1.1 years (5–12 years); 5 cases in the left knee and 9 cases in the right knee; the mean operative time was 19.2 ± 2.7 min (10–25 min); and the mean follow-up time was 15.1 ± 2.4 months (12–24 months). There was no intraoperative vascular or nerve injury and no incisional exudate infection. Postoperatively, posterior knee symptoms disappeared in the children, Rauschning and Lindgren scores significantly improved, and no recurrence signs were observed on MRI.ConclusionsThis study determined that the arthroscopic three-channel minimally invasive technique is effective and safe for treating popliteal cysts in children, making it worthy of clinical promotion.

Safety and risk analysis of total resection surgery for thoracic and lumbar spinal tumors: a decadal analysis of 103 cases

Study designRetrospective cohort study.PurposeTo explore the complications and risk factors for total resection (TR) of primary thoracic and lumbar spinal tumors over the past decade at our institution.MethodsPatients meeting inclusion criteria (primary spinal tumors, thoracic or lumbar location, TR at our center) were included. Demographic characteristics, surgical data, perioperative complications and management results were reviewed. Patients were stratified by tumor site, the number of excised segments, and recurrence status to elucidate distinctive characteristics.ResultsThe cohort comprised 103 patients, with a mean age of 35.8 years. On average, 1.83 vertebral segments were resected per patient. Perioperative complications were substantial, totaling 166 events, with 71 classified as major and 95 as minor, yielding an average of 1.61 complications per patient. No perioperative deaths occurred, but 79 patients (76.7%) experienced at least one complication. Multiple vertebral sections correlated with a higher complication rate (P = 0.031), and lumbar surgeries exhibited elevated risks of large vascular injury (P = 0.001), neurological deterioration, and cerebrospinal fluid leakage compared to thoracic cases. Conversely, thoracic spinal procedures showed a higher rate of pleural effusion (P = 0.004). Binary logistics stepwise regression identified multi-segmental resection as the independent risk factor for major perioperative complications.ConclusionsTR of primary spinal tumors is associated with a high perioperative complication rate, although most events have a favorable prognosis. Complication characteristics vary based on the surgical site, number of excised segments, and surgical history. A nuanced preoperative evaluating approach considering patient age, surgical segments, and extent of resection is crucial.

Honokiol protects against diabetic retinal microvascular injury via sirtuin 3-mediated mitochondrial fusion

IntroductionMitochondrial dysfunction and oxidative stress play important roles in diabetic retinal vascular injuries. Honokiol (HKL) is a small-molecule polyphenol that exhibits antioxidant effects and has a beneficial effect in diabetes. This study aimed to explore the potential ability of HKL to ameliorate vascular injury in diabetic retinopathy (DR) and its possible mechanisms of action.MethodsThe effect of HKL was evaluated in vascular injury in an in vivo type 2 diabetic (db/db) mouse model. In vitro, retinal microvascular endothelial cells were treated with high glucose (HG) to simulate the pathological diabetic environment. Cell viability, expression of apoptosis-related proteins, cellular reactive oxygen species, mitochondrial membrane potential, and morphological changes in the mitochondria were examined.ResultsThe diabetic mice exhibited severe retinal vascular damage, including vascular leakage in vivo and capillary endothelial cell apoptosis in vitro. HKL reversed the retinal vascular leakage in the diabetic mice. In vitro, HKL improved retinal capillary endothelial cell viability, decreased apoptosis, and reversed the HG-induced increased cellular oxidative stress and mitochondrial fragmentation. The sirtuin 3 (SIRT3) inhibitor 3-TYP blocked all the in vivo and in vitro protective effects of HKL against diabetic retinal vascular leakage and capillary endothelium and eliminated the decrease in oxidative stress levels and reduction of mitochondrial fragmentation.DiscussionIn conclusion, these findings suggest that HKL inhibits vascular injury in DR, which was likely achieved through SIRT3-mediated mitochondrial fusion. This study provides a potential new strategy for the treatment of DR.

Luteolin Protects against Vascular Calcification by Modulating SIRT1/CXCR4 Signaling Pathway and Promoting Autophagy.

Vascular calcification (VC) is a common pathological manifestation of atherosclerosis, hypertension, diabetes vascular disease, vascular injury, chronic kidney disease and aging, which is mainly manifested as increased stiffness of the vascular wall. Oxidative stress and autophagy dysfunction are key factors in the pathogenesis of vascular calcification, but the specific mechanisms and the therapeutic strategy of vascular calcification have not been clarified. In the present study, Sirtuin 1 (SIRT1) was screened as the therapeutic targets for vascular calcification by the bioinformatics. SIRT1 is a nicotinamide adenine dinucleotide, which plays an important role in inhibiting oxidative stress and promoting autophagy. Luteolin(LUT), a kind of natural tetrahydroxyl flavonoid, exists in many plants and has many pharmacological effects such as anti-oxidation and anti-apoptosis. We have reported that luteolin has certain anti-osteoporosis effects in the previous study, and it is accepted that the development of vascular calcification is similar to bone formation, indicating that luteolin may also resist vascular calcification. And luteolin is known to activate SIRT1 to some extent. Moreover, the molecular docking analysis predicted that SIRT1 could bind directly to luteolin. Therefore, the purpose of this study was to investigate the potential role of luteolin in inhibiting oxidative stress and promoting autophagy during vascular calcification via modulating SIRT1 expression. The results showed that luteolin significantly improved vascular calcification induced by a high-fat diet (HFD) and vitamin D3 in rats in vivo. In addition, luteolin significantly repressed the formation of mineralized nodules and ALP activity in H2O2-treated A7r5 cells. Luteolin reduced the level of MDA, LDH and ROS generation, inhibited the protein expression of cleaved caspase-3, cleaved caspase-9, β-catenin and BMP-2 in the aortic tissue of the rat and rat smooth muscle cells (A7r5) treated with hydrogen peroxide. At the same time, luteolin could promote the expression of autophagy related proteins. Moreover, luteolin also produced effects to increase the protein expression levels of SIRT1 more than 2 times both in vivo and in vitro. In terms of mechanism, luteolin attenuated vascular calcification by inhibiting oxidative stress and improving autophagy level, via modulating SIRT1 / CXCR4 signaling pathway. In conclusion, this experiment for the first time revealed that LUT protected against VC via modulating SIRT1 / CXCR4 signaling pathway to promote autophagy and inhibit vascular calcification and may be developed as a new therapeutic agent for vascular calcification and atherosclerosis.

A novel model of cardiovascular–kidney–metabolic syndrome combining unilateral nephrectomy and high-salt–sugar–fat diet in mice

The aim of this study was to explore biological interaction and pathophysiology mechanisms in a new mouse model of cardiovascular–kidney–metabolic (CKM) syndrome, induced by chronic moderate renal failure in combination with consumption of a customized Western diet rich in carbohydrates, fat and salt. Male C57BL/6J mice were subjected to unilateral nephrectomy, fed a customized Western diet rich not only in sugar and fat but also in salt, and followed for 12 weeks or 20 weeks. Sham-operated mice on a standard chow served as healthy controls. Body composition, weight gain, glucose metabolism, fat distribution, blood pressure, cardiac function, vascular reactivity, renal function, inflammation and mitochondrial function were measured and combined with biochemical and histopathological analyses. The novel triple-hit model of CKM syndrome showed signs and symptoms of metabolic syndrome, disturbed glucose metabolism, impaired adipocyte physiology and fat redistribution, cardiovascular dysfunction, renal damage and dysfunction, systemic inflammation, elevated blood pressure and cardiac remodeling. The pathological changes were more pronounced in mice after prolonged exposure for 20 weeks, but no deaths occurred. In the present mouse model of CKM syndrome, profound and significant metabolic, cardiac, vascular and renal dysfunctions and injuries emerged by using a Western diet rich not only in fat and carbohydrates but also in salt. This multisystem disease model could be used for mechanistic studies and the evaluation of new therapeutic strategies.

Follow-up strategies after non-operative treatment of traumatic splenic injuries: a systematic review.

Blunt trauma often results in splenic injuries, with non-operative management (NOM) being the preferred approach for stable patients. Following NOM, splenic vascular injuries, such as pseudoaneurysms, may arise, prompting radiological follow-up. However, a consensus on optimal radiological follow-up strategies is lacking. This systematic review evaluates existing evidence on radiological follow-up post-NOM for traumatic splenic injuries. Conducting a systematic review following updated PRISMA guidelines, we searched MEDLINE, Embase, The Cochrane Library, and trial registries from January 2010 to March 2023. Inclusion criteria covered studies on radiological follow-up for blunt splenic injuries. Out of 5794 studies, 17 were included involving 3392 patients. Various radiological modalities were used, with computed tomography (CT) being the most common. Vascular injuries occurred in 4.5% of patients, with most pseudoaneurysms diagnosed on day 2-6 post-trauma, and leading to intervention in 60% of these cases. Thirteen studies recommended routine follow-up, with six favouring CT, and seven supporting radiation-free modalities. Four studies proposed follow-up based on clinical indications, initial findings, or symptoms. Recommendations for specific timing of radiological follow-up ranged from 48h to seven days post-injury. Regarding AAST grading, nine studies recommended follow-up for injury grade III and higher. Limited high-quality evidence exists on radiological follow-up in isolated blunt splenic injuries, causing uncertainty in clinical practice. However, our review suggests a reasonable need for follow-up, with contrast-enhanced ultrasound emerging as a promising alternative to CT. Specific timing and criteria for follow-up remain unresolved, highlighting the need for high-quality prospective studies to address these knowledge gaps.

The novel anthraquinone compound Kanglexin prevents endothelial-to-mesenchymal transition in atherosclerosis by activating FGFR1 and suppressing integrin β1/TGFβ signaling.

Endothelial-mesenchymal transition (EndMT) disrupts vascular endothelial integrity and induces atherosclerosis. Active integrin β1 plays a pivotal role in promoting EndMT by facilitating TGFβ/Smad signaling in endothelial cells. Here, we report a novel anthraquinone compound, Kanglexin (KLX), which prevented EndMT and atherosclerosis by activating MAP4K4 and suppressing integrin β1/TGFβ signaling. First, KLX effectively counteracted the EndMT phenotype and mitigated the dysregulation of endothelial and mesenchymal markers induced by TGFβ1. Second, KLX suppressed TGFβ/Smad signaling by inactivating integrin β1 and inhibiting the polymerization of TGFβR1/2. The underlying mechanism involved the activation of FGFR1 by KLX, resulting in the phosphorylation of MAP4K4 and Moesin, which led to integrin β1 inactivation by displacing Talin from its β-tail. Oral administration of KLX effectively stimulated endothelial FGFR1 and inhibited integrin β1, thereby preventing vascular EndMT and attenuating plaque formation and progression in the aorta of atherosclerotic Apoe-/- mice. Notably, KLX (20 mg/kg) exhibited superior efficacy compared with atorvastatin, a clinically approved lipid-regulating drug. In conclusion, KLX exhibited potential in ameliorating EndMT and retarding the formation and progression of atherosclerosis through direct activation of FGFR1. Therefore, KLX is a promising candidate for the treatment of atherosclerosis to mitigate vascular endothelial injury.

The Occurrence of Senescence in the Arteriovenous Fistula in the Rat.

Maturational failure of dialysis arteriovenous fistulas (AVFs) not uncommonly occurs and is of considerable and timely importance. Our prior studies demonstrate that senescence, a phenotypic process that promotes vascular and other diseases, occurs in the murine AVF. In the present study, we examined whether senescence also occurs in the rat AVF model and the effect of compounds that inhibit or accelerate senescence. The rat AVF was created in the femoral vessels by an end vein-side artery anastomosis. We assessed in the AVF the expression of critical drivers of senescence, specifically, the cell cycle inhibitors p16Ink4a and p21Cip1, and such indices of a senescence phenotype as senescence-associated β-galactosidase (SA-β-gal) activity, SA-β-gal staining, and a senescence-associated secretory phenotype (SASP). We examined the effects of compounds that retard or accelerate senescence on AVF blood flow. The AVF evinced upregulation of p16Ink4a and p21Cip1 when assessed 3 days after AVF creation. The AVF also demonstrated increased SA-β-gal activity in the artery and vein; staining for SA-β-gal in the AVF artery, anastomosis, and vein; and a prominent SASP. Fisetin, an established senolytic that is protective in other models of vascular injury, when administered for 3 weeks, increased AVF blood flow and outward remodeling. Hemin, when administered for 3 weeks, decreased AVF blood flow. We demonstrate that hemin is a novel inducer of a senescence phenotype in endothelial cells, as reflected by several senescence indices. However, when administered relatively acutely (for 5 days) hemin increased AVF blood flow via HO-dependent mechanisms, as the latter was entirely prevented by a competitive inhibitor of HO activity. The rat AVF exhibits senescence within 3 days of its creation. Chronic administration of a senolytic compound (fisetin) increases AVF blood flow, whereas chronic administration of a pro-senescence compound (hemin) decreases AVF blood flow.

Transient High Salt Intake Promotes T-Cell-Mediated Hypertensive Vascular Injury.

Dietary high salt (HS) intake has a strong impact on cardiovascular diseases. Here, we investigated the link between HS-aggravated immune responses and the development of hypertensive vascular disease. ApolipoproteinE-deficient mice were transiently treated with HS (1% NaCl) via drinking water for 2 weeks, followed by a washout period, and subsequent Ang II (angiotensin II) infusion (1000 ng/kg per min for 10 days) to induce abdominal aortic aneurysms/dissections and inflammation. While transient HS intake alone triggered nonpathologic infiltration of activated T cells into the aorta, subsequent Ang II infusion increased mortality and the incidence of abdominal aortic aneurysms/dissections and atherosclerosis compared with hypertensive control mice. There were no differences in blood pressure between both groups. In transient HS-treated hypertensive mice, the aortic injury was associated with increased inflammation, accumulation of neutrophils, monocytes, CD69+CD4+ T cells, as well as CD4+ and CD8+ memory T cells. Mechanistically, transient HS intake increased expression levels of aortic RORγt as well as splenic CD4+TH17 and CD8+TC1 T cells in Ang II-treated mice. Isolated aortas of untreated mice were incubated with supernatants of TH17, TH1, or TC1 cells polarized in vitro under HS or normal conditions which revealed that secreted factors of HS-differentiated TH17 and TC1 cells, but not TH1 cells accelerated endothelial dysfunction. Our data suggest that transient HS intake induces a subclinical T-cell-mediated aortic immune response, which is enhanced by Ang II. We propose a 2-hit model, in which HS acts as a predisposing factor to enhance hypertension-induced TH17 and TC1 polarization and aortic disease.

Impact of Age on the Occurrence of Vascular Complications in Patients Undergoing Anterior Lumbar Approach Surgery.

Retrospective cohort study. To investigate the impact of age on the incidence of vascular complications in patients undergoing anterior lumbar approach surgery. Anterior approach lumbar spinal surgery may facilitate the use of intervertebral devices with larger endplate coverage and increased lordosis. Despite the advantages of this approach, risks related to vascular injury in older patients have been described in the literature. In total, 751 consecutive patients with degenerative spinal pathology who underwent stand-alone anterior lumbar interbody fusion (ALIF), ALIF combined with posterior fusion and/or instrumentation (360), total disc replacement, or hybrid procedures (ALIF and total disc replacement) were included. Data collected included general patient descriptive data, surgery details, intraoperative vascular injury, and postoperative vascular complications (deep vein thrombosis and/or pulmonary embolism). Rates of vascular complications were compared across age groups. In addition, the mean age of patients was compared between those with versus without vascular complications. Overall mean age was 50.4 years (range: 20-83 yr). The mean estimated blood loss was 91.3mL (range: 10-2800mL). A total of 15 patients, 2.0%, had vascular complications. There were 10 cases (1.3%) of intraoperative injury to iliac arteries or iliolumbar veins (mean blood loss was 721mL, and all were repaired intraoperatively). Postoperatively, 6 patients (0.8%) developed deep vein thrombosis and/or pulmonary embolism (one patient had both). With respect to age, there were no significant differences in rates of intraoperative, postoperative, or combined vascular complication rates across the age group ( P > 0.38). In addition, there were no statistically significant differences in the mean ages of patients with versus those without vascular complications ( P > 0.17). Overall incidence of vascular complications was 2.0%. No relationship between vascular complications and age was demonstrated. These data suggest that increased age may not necessarily be an absolute contraindication for anterior lumbar approach surgery. Level III.

Penetrating neck trauma” - Enigma to surgeons: A case report with review of literature

: We report for the first time a case of penetrating injury to carotid artery by a stone piece during welding using hammer.: A 26, year old male labourer presented with a penetrating neck injury by a stone piece. As the patient was stable, NCCT neck was done which revealed a metallic foreign body obliterating the right carotid space. CT Angiography was also done to rule out any vascular injury. The patient underwent neck exploration during which foreign body was removed and right carotid artery repair was done with 4-0 prolene. : The patient had no complications and showed no sequalae from this injury during follow up.: CT angiography should be done in all patients who are stable to rule out injury to great vessels before neck exploration .

Exosomes from hypoxic urine-derived stem cells facilitate healing of diabetic wound by targeting SERPINE1 through miR-486-5p

Vascular pathologies and injuries are important factors for the delayed wound healing in diabetes. Previous studies have demonstrated that hypoxic environments could induce formation of new blood vessels by regulating intercellular communication and cellular behaviors. In this study, we have enhanced the angiogenic potential of exosomes by subjecting urine-derived stem cells (USCs) to hypoxic preconditioning. To prolong the retention of exosomes at the wound site, we have also engineered a novel dECM hydrogel termed SISMA, which was modified from porcine small intestinal submucosa (SIS). For its rapid and controllable gelation kinetics, excellent biocompatibility, and exosome release capability, the SISMA hydrogel has proven to be a reliable delivery vehicle for exosomes. The hypoxia-induced exosomes-loaded hydrogel has promoted endothelial cell proliferation, migration, and tube formation. More importantly, as evidenced by significant in vivo vascular regeneration in the early stages post-injury, it has facilitated tissue repair. This may because miR-486–5p in H-exo inhibit SERPINE1 activity in endothelial cell. Additionally, miRNA sequencing analysis suggested that the underlying mechanism for enhanced angiogenesis may be associated with the activation of classical HIF-1α signaling pathway. In summary, our study has presented a novel non-invasive, cell-free therapeutic approach for accelerating diabetes wound healing and development of a practical and efficient exosomes delivery platform.

Mechanisms of Lung Endothelial Cell Injury and Survival in Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is a progressive, chronic, and incurable inflammatory pulmonary vascular disease characterized by significant sex bias and largely unexplored microbial-associated molecular mechanisms that may influence its development and sex prevalence across various subgroups. PAH can be subclassified as idiopathic, heritable, or associated with conditions such as connective tissue diseases, congenital heart defects, liver disease, infections, and chronic exposure to drugs or toxins. During PAH progression, lung vascular endothelial cells (ECs) undergo dramatic morphofunctional transformations in response to acute and chronic inflammation. These transformations include the appearance and expansion of abnormal vascular cell phenotypes such as those derived from apoptosis-resistant cell growth and endothelial-to-mesenchymal transition (EndoMT). Compelling evidence indicates that these endothelial phenotypes seem to be triggered by chronic lung vascular injury and dysfunction, often characterized by reduced secretion of vasoactive molecules like nitric oxide (NO) and exacerbated response to vasoconstrictors such as Endothelin-1 (ET-1); both long-term known contributors of PAH pathogenesis. This review sheds light on the mechanisms of EC dysfunction, apoptosis, and EndoMT in PAH, aiming to unravel the intricate interactions between ECs, pathogens, and other cell types that drive the onset and progression of this devastating disease. Ultimately, we hope to provide an overview of the complex functions of lung vascular ECs in PAH, inspiring novel therapeutic strategies that target these dysfunctional cells to improve the treatment landscape for PAH, particularly in the face of current and emerging global pathogenic threats.

Chronic stress in adulthood results in microvascular dysfunction and subsequent depressive-like behavior

Depression is a prevalent mental disorder characterized by unknown pathogenesis and challenging treatment. Recent meta-analyses reveal an association between cardiovascular risk factors and an elevated risk of depression. Despite this, the precise role of vascular injury in depression development remains unclear. In this investigation, we assess vascular system function in three established animal models of depression— chronic unpredictable mild stress (CUMS), chronic social defeat stress (CSDS) and maternal separation (MS)—utilizing ultrasonography and laser Doppler measurement. All three model animals exhibit anhedonia and despair-like behavior. However, significant microvascular dysfunction (not macrovascular) is observed in animals subjected to CUMS and CSDS models, while such dysfunction is absent in the MS model. Statistical analysis further indicates that microcirculation dysfunction is not only associated with depression-like behavior but is also intricately involved in the development of depression in the CUMS and CSDS models. Furthermore, our study has proved for the first time that endothelial nitric oxide synthase-deficient (eNOS+/−) mice, which is a classic model of vascular endothelial injury, showed depression-like behavior which occurred two months later than microvascular dysfunction. Notably, the mitigation of microvascular dysfunction successfully reverses depression-like behavior in eNOS+/− mice by enhancing nitric oxide production. In conclusion, this study unveils the pivotal role of microvascular dysfunction in the onset of depression induced by chronic stress in adulthood and proposes that modulating microvascular function may serve as a potential intervention in the treatment of depression.

MiR-148a-3p mitigation of coronary artery disease through PCSK9/NF-κB inhibition of vascular endothelial cell injury.

Coronary artery disease (CAD) causes myocardial ischemia, narrowing or occlusion of the lumen. Although great progress has been made in the treatment of CAD, the existing treatment methods do not meet the clinical needs, so it is urgent to find new treatment methods. The aim of this study was to investigate the mechanism of action of miR-148a-3p in alleviating CAD by inhibiting vascular endothelial cell injury and to provide new ideas for the treatment of CAD. A cell model was constructed by lipopolysaccharide (LPS) induction of vascular endothelial cells, and a CAD rat model was established by a high-fat diet and intraperitoneal injection of posterior pituitary hormone. Relevant indices were detected by RT-qPCR, ELISA, Western blot, MTT, and flow cytometry. The results indicate that in LPS-induced vascular endothelial cell assays, miR-148a-3p inhibited the upregulation of PCSK9, thereby suppressing the NF-κB signaling pathway and promoting vascular endothelial cell proliferation. Overexpression of PCSK9 and the addition of NF-κB signaling pathway activator increased vascular endothelial cell apoptosis. In animal experiments, miR-148a-3p alleviated the symptoms of CAD rats, whereas overexpression of PCSK9 promoted apoptosis and increased atheromatous plaque area in CAD rats. In conclusion, miR-148a-3p inhibits the NF-κB signaling pathway through downregulation of PCSK9, thereby protecting vascular endothelial cells and alleviating CAD.