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Phytomedicine : International Journal... Jun 2024Hypoxic pulmonary vascular remodeling (HPVR) is a key pathological feature of hypoxic pulmonary hypertension (HPH). Oxygen-sensitive potassium (K) channels in pulmonary...
BACKGROUND
Hypoxic pulmonary vascular remodeling (HPVR) is a key pathological feature of hypoxic pulmonary hypertension (HPH). Oxygen-sensitive potassium (K) channels in pulmonary artery smooth muscle cells (PASMCs) play a crucial role in HPVR. Luteolin (Lut) is a plant-derived flavonoid compound with variety of pharmacological actions. Our previous study found Lut alleviated HPVR in HPH rat.
PURPOSE
To elucidate the mechanism by which Lut mitigated HPVR, focusing on oxygen-sensitive voltage-dependent potassium channel 1.5 (Kv1.5).
METHODS
HPH rat model was established using hypobaric chamber to simulate 5000 m altitude. Isolated perfused/ventilated rat lung, isolated pulmonary arteriole ring was utilized to investigate the impact of Lut on K channels activity. Kv1.5 level in lung tissue and pulmonary arteriole of HPH rat was assessed. CyclinD1, CDK4, PCNA, Bax, Bcl-2, cleaved caspase-3 levels in lung tissue of HPH rat were tested. The effect of Lut on Kv1.5, cytoplasmic free calcium concentration ([Ca]), CyclinD1, CDK4, PCNA, Bax/Bcl-2 was examined in PASMCs under hypoxia, with DPO-1 as a Kv1.5 specific inhibitor. The binding affinity between Lut and Kv1.5 in PASMCs was detected by drug affinity responsive target stability (DARTS). The overexpression of KCNA5 gene (encoding Kv1.5) in HEK293T cells was utilized to confirm the interaction between Lut and Kv1.5. Furthermore, the impact of Lut on mitochondrial structure, SOD, GSH, GSH-Px, MDA and HIF-1α levels were evaluated in lung tissue of HPH rat and PASMCs under hypoxia.
RESULTS
Lut dilated pulmonary artery by directly activating Kv and Ca-activated K channels (K) in smooth muscle. Kv1.5 level in lung tissue and pulmonary arteriole of HPH rat was upregulated by Lut. Lut downregulated CyclinD1, CDK4, PCNA while upregulating Bax/Bcl-2/caspase-3 axis in lung tissue of HPH rat. Lut decreased [Ca], reduced CDK4, CyclinD1, PCNA, increased Bax/Bcl-2 ratio, in PASMCs under hypoxia, by upregulating Kv1.5. The binding affinity and the interaction between Lut and Kv1.5 was verified in PASMCs and in HEK293T cells. Lut also decreased [Ca] and inhibited proliferation via targeting Kv1.5 of HEK293T cells under hypoxia. Furthermore, Lut protected mitochondrial structure, increased SOD, GSH, GSH-Px, decreased MDA, in lung tissue of HPH rat. Lut downregulated HIF-1α level in both lung tissue of HPH rat and PASMCs under hypoxia.
CONCLUSION
Lut alleviated HPVR by promoting vasodilation of pulmonary artery, reducing cellular proliferation, and inducing apoptosis through upregulating of Kv1.5 in PASMCs.
PubMed: 38941817
DOI: 10.1016/j.phymed.2024.155840 -
Orthopaedics & Traumatology, Surgery &... Jun 2024The modified Stoppa approach is gradually becoming the gold standard in pelvic ring and acetabulum surgery. One of the potential intraoperative complications is vascular...
INTRODUCTION
The modified Stoppa approach is gradually becoming the gold standard in pelvic ring and acetabulum surgery. One of the potential intraoperative complications is vascular injury. The aim of this study was to identify the level of division of common iliac vessels with respect to a bone landmark, their inter-individual variability and their correlation with morphological criteria.
MATERIAL AND METHODS
This was a single-center continuous retrospective study of patients who had preoperative CT angiography for pelvic fracture between February 2017 and May 2018. The level of arterial and venous division and the angle of vein division were measured bilaterally for each patient from the most antero-inferior part of the sacroiliac joint on multiplanar reconstruction and standardized analysis. Relationships with morphological data (age, gender, BMI, height), anterior column fracture and deep venous thrombosis were analyzed.
RESULTS
The right arterial division level was 50±16mm (-2.35; 96) from the landmark and the left arterial division level 44±14mm (0; 80). The right venous division level was 30±12mm (-9; 75) and the left venous division level 30±13mm (-5; 66). The right venous bifurcation angle was 65±18° (22; 119) and the left venous bifurcation angle 68±17° (18; 117). The arterial division level was significantly higher on the right side (p=0.007). There were no significant correlations with morphological data.
CONCLUSION
The great inter-individual variability of iliac vessels should prompt analysis of their morphology on routine imaging when planning pelvic surgery using the modified Stoppa approach, in order to anticipate the risk of bleeding.
LEVEL OF EVIDENCE
IV; cases series.
PubMed: 38936697
DOI: 10.1016/j.otsr.2024.103922 -
Genes Jun 2024The ring finger protein 213 gene (RNF213) is involved in several vascular diseases, both intracranial and systemic ones. Some variants are common in the Asian population...
The ring finger protein 213 gene (RNF213) is involved in several vascular diseases, both intracranial and systemic ones. Some variants are common in the Asian population and are reported as a risk factor for moyamoya disease, intracranial stenosis and intracranial aneurysms. Among intracranial vascular diseases, both moyamoya disease and intracranial artery dissection are more prevalent in the Asian population. We performed a systematic review of the literature, aiming to assess the rate of RNF213 variants in patients with spontaneous intracranial dissections. Four papers were identified, providing data on 53 patients with intracranial artery dissection. The rate of RNF213 variants is 10/53 (18.9%) and it increases to 10/29 (34.5%), excluding patients with vertebral artery dissection. All patients had the RNF213 p.Arg4810Lys variant. RNF213 variants seems to be involved in intracranial dissections in Asian cohorts. The small number of patients, the inclusion of only patients of Asian descent and the small but non-negligible coexistence with moyamoya disease familiarity might be limiting factors, requiring further studies to confirm these preliminary findings and the embryological interpretation.
Topics: Humans; Adenosine Triphosphatases; Aortic Dissection; Asian People; Genetic Predisposition to Disease; Intracranial Aneurysm; Moyamoya Disease; Polymorphism, Single Nucleotide; Ubiquitin-Protein Ligases
PubMed: 38927660
DOI: 10.3390/genes15060725 -
Skin Research and Technology : Official... Jul 2024Wound healing monitoring and timely decision-making are critical for wound classification. Tryptophan (Tr) intrinsic fluorescence, detected at 295/340 nm, provides a...
BACKGROUND
Wound healing monitoring and timely decision-making are critical for wound classification. Tryptophan (Tr) intrinsic fluorescence, detected at 295/340 nm, provides a noninvasive approach for wound assessment. Our previous work demonstrated that this autofluorescence is associated with keratinocytes in a highly proliferative state in vitro.
OBJECTIVE
We investigated the correlation between Tr fluorescence and key wound healing parameters, including re-epithelialization, fibrosis, neovascularization, and acute and chronic inflammation, using a rabbit model.
METHODS
Seven rabbits underwent wound healing assessment over a 15-day period. We employed histological analysis from central and marginal biopsies, and UV fluorescence imaging captured by a monochromatic near-UV sensitive camera equipped with a passband optical filter (340 nm/12 nm). Excitation was achieved using a 295 nm LEDs ring lamp. Normalized fluorescence values were correlated with histological measurements using Pearson correlation.
RESULTS
The UV fluorescence strongly exhibited a strong correlation with re-epithelization (r = 0.8) at the wound edge, with peak intensity observed between the sixth and ninth days. Notably, wound-healing dynamics differed between the wound center and edge, primarily attributed to variations in re-epithelialization, neovascularization, and chronic inflammation.
CONCLUSION
Our findings highlight the presence of autofluorescence at 295/340 nm during wound healing, demonstrating a robust association with re-epithelialization. This excitation/emission signal holds promise as a valuable noninvasive strategy for monitoring wound closure, re-epithelialization, and other biological processes where Tr plays a pivotal role.
Topics: Animals; Rabbits; Tryptophan; Re-Epithelialization; Wound Healing; Disease Models, Animal; Fluorescence; Skin; Optical Imaging; Inflammation; Ultraviolet Rays
PubMed: 38923076
DOI: 10.1111/srt.13834 -
Veterinary Sciences Jun 2024A 13-year-old spayed female cocker spaniel was presented with a 2-month history of swelling in several digits and intermittent hindlimb lameness. Radiographs revealed...
A 13-year-old spayed female cocker spaniel was presented with a 2-month history of swelling in several digits and intermittent hindlimb lameness. Radiographs revealed marked soft-tissue swelling and periosteal new bone formation without cortical bone destruction, characteristic of hypertrophic osteopathy (HO), in the distal parts of all extremities except for the right forelimb. However, no notable findings were detected in thoracic radiographs. An ultrasonography indicated cranial bladder wall thickening, which resolved following antibiotic therapy. Computed tomographic angiography identified a potential underlying cause as an aberrant right subclavian artery (ARSA) originating from the aortic arch, compressing the esophagus and causing mild esophageal cranial dilation to the aberrant vessel. No other intrathoracic or neoplastic lesions were observed. Gastrointestinal symptoms, such as regurgitation, were absent. Although an ARSA was likely the cause of HO, surgical correction was declined by the owner. To the best of our knowledge, this is the first reported case of HO concurrent with ARSA in dogs.
PubMed: 38922010
DOI: 10.3390/vetsci11060263 -
The Archives of Bone and Joint Surgery 2024The aim of this study is to provide a radiologic description of periacetabular vascularization. A computed tomography angiography was used to analyze the vascularization...
The aim of this study is to provide a radiologic description of periacetabular vascularization. A computed tomography angiography was used to analyze the vascularization patterns of the periacetabular region, describing for the first time "in vivo" the periacetabular branches of the superior and inferior gluteal artery, obturator artery, and of the medial circumflex femoral artery. The analysis revealed the possibility of visualizing clearly all the previously described vessels of the aforementioned arteries. Both acetabular and supra-acetabular arteries, the rami of the OA directed to the lamina quadrilateral, and the rami of the IGA directed to the posterior wall were identified. In conclusion, understanding the periacetabular vascularization patterns is pivotal for effective clinical decision-making in pelvic trauma, and conservative and reconstructive surgery of the hip. The radiologic description provided in this study, along with the associated literature review, offers valuable insights into the clinical implications of periacetabular vascularization.
PubMed: 38919742
DOI: 10.22038/ABJS.2024.75243.3480 -
The Journal of Thoracic and... Jun 2024In remodeling valve sparing root replacement with external annuloplasty, we compare long-term outcomes of calibrated expansible Extra-Aortic Ring to homemade Dacron ring.
OBJECTIVES
In remodeling valve sparing root replacement with external annuloplasty, we compare long-term outcomes of calibrated expansible Extra-Aortic Ring to homemade Dacron ring.
METHODS
All patients (2003-2020) operated for root aneurysm with/without AI were included. The standardized CAVIAAR technique was root remodeling and external annuloplasty ring, with Extra-Aortic Ring or homemade Dacron ring.
RESULTS
Among 486 patients (age: 52.3±14.0 years) operated for root aneurysm, 375 (repair rate: 77.1%) underwent root remodeling with annuloplasty (Extra-Aortic Ring (n=289) vs Dacron ring (n=86)). At 10 years (median follow-up: 4.08 years, IQR [1.95,7.61]), unmatched and matched analysis showed that patients with Extra-Aortic Ring had higher survival, similar to the general population (93.3% vs 79.9%, p=0.097), lower reoperation incidence (2.0% vs 9.7%, p=0.0098) and lower AI grade>2 recurrence (1.9% vs 11.2%, p=0.0042), compared to patients with Dacron ring. Mixed-effect model showed that with Extra-Aortic Ring annuloplasty, annular dilation over time (p=0.0033) was prevented and, compared to homemade Dacron ring, root expansibility was better preserved (3.22% vs 2.12%, p=0.002) and mean transvalvular gradient was lower (6.58mmHg vs 7.94mmHg, p=0.001). Tricuspid and bicuspid valves with Extra-Aortic Ring had similar reoperation (4.3% vs 0.85%, p=0.65) and AI grade>2 incidence (2.7% vs 1.2%, p=0.61), expansibility (p=0.29) and diameter (p=0.47), while mean transvalvular gradient was lower for tricuspid valves (5.58mmHg vs 7.60mmHg, p=0.004).
CONCLUSIONS
Valve sparing root remodeling with calibrated expansible Extra-Aortic Ring annuloplasty improves outcomes of reoperation and recurrent AI, compared to homemade Dacron ring. It prevents dilation and maintains physiological root dynamics for durable valve repair.
PubMed: 38914371
DOI: 10.1016/j.jtcvs.2024.06.013 -
Urology Case Reports Jul 2024Penile strangulation secondary to utilization of a constrictive ring is a rare urologic emergency that requires urgent decompression to prevent prolonged vascular...
Penile strangulation secondary to utilization of a constrictive ring is a rare urologic emergency that requires urgent decompression to prevent prolonged vascular obstruction resulting in necrosis and gangrene. Current literature is mainly comprised of case presentations that focus on management in the acute setting via removal of the ring. Herein, we describe surgical management of a patient who presents in delayed fashion after self-removal of the constrictive ring. We discuss our penectomy-sparing technique of debridement and split thickness skin graft.
PubMed: 38911466
DOI: 10.1016/j.eucr.2024.102762 -
Frontiers in Cardiovascular Medicine 2024In hypertension (HTN), biomechanical stress may drive matrix remodeling through dysfunctional VSMC activity. Prior evidence has indicated VSMC tension-induced signaling...
INTRODUCTION
In hypertension (HTN), biomechanical stress may drive matrix remodeling through dysfunctional VSMC activity. Prior evidence has indicated VSMC tension-induced signaling through the serum and glucocorticoid inducible kinase-1 (SGK-1) can impact cytokine abundance. Here, we hypothesize that SGK-1 impacts production of additional aortic pathologic markers (APMs) representing VSMC dysfunction in HTN.
METHODS
Aortic VSMC expression of APMs was quantified by QPCR in cyclic biaxial stretch (Stretch) +/- AngiotensinII (AngII). APMs were selected to represent VSMC dedifferentiated transcriptional activity, specifically Interleukin-6 (IL-6), Cathepsin S (CtsS), Cystatin C (CysC), Osteoprotegerin (OPG), and Tenascin C (TNC). To further assess the effect of tension alone, abdominal aortic rings from C57Bl/6 WT mice were held in a myograph at experimentally derived optimal tension (OT) or OT + 30% +/-AngII. Dependence on SGK-1 was assessed by treating with EMD638683 (SGK-1 inhibitor) and APMs were measured by QPCR. Then, WT and smooth muscle cell specific SGK-1 heterozygous knockout (SMC-SGK-1KO) mice had AngII-induced HTN. Systolic blood pressure and mechanical stress parameters were assessed on Day 0 and Day 21. Plasma was analyzed by ELISA to quantify APMs. Statistical analysis was performed by ANOVA.
RESULTS
In cultured aortic VSMCs, expression of all APMs was increased in response to biomechanical stimuli (Stretch +/-AngII,). Integrating the matrix contribution to signal transduction in the aortic rings led to IL-6 and CysC demonstrating SGK-1 dependence in response to elevated tension and interactive effect with concurrent AngII stimulation. CtsS and TNC, on the other hand, primarily responded to AngII, and OPG expression was unaffected in aortic ring experimentation. Both mouse strains had >30% increase in blood pressure with AngII infusion, reduced aortic distensibility and increased PPV, indicating increased aortic stiffness. In WT + AngII mice, IL-6, CtsS, CysC, and TNC plasma levels were significantly elevated, but these APMs were unaffected by HTN in the SMC-SGK-1KO +AngII mice, suggesting SGK-1 plays a major role in VSMC biomechanical signaling to promote dysfunctional production of selected APMs.
CONCLUSION
In HTN, changes in the plasma levels of markers associated with aortic matrix homeostasis can reflect remodeling driven by mechanobiologic signaling in dysfunctional VSMCs, potentially through the activity of SGK-1. Further defining these pathways may identify therapeutic targets to reduce cardiovascular morbidity and mortality.
PubMed: 38903966
DOI: 10.3389/fcvm.2024.1359734 -
Deletion of endothelial IGFBP5 protects against ischaemic hindlimb injury by promoting angiogenesis.Clinical and Translational Medicine Jun 2024Angiogenesis is critical for forming new blood vessels from antedating vascular vessels. The endothelium is essential for angiogenesis, vascular remodelling and...
BACKGROUND
Angiogenesis is critical for forming new blood vessels from antedating vascular vessels. The endothelium is essential for angiogenesis, vascular remodelling and minimisation of functional deficits following ischaemia. The insulin-like growth factor (IGF) family is crucial for angiogenesis. Insulin-like growth factor-binding protein 5 (IGFBP5), a binding protein of the IGF family, may have places in angiogenesis, but the mechanisms are not yet completely understood. We sought to probe whether IGFBP5 is involved in pathological angiogenesis and uncover the molecular mechanisms behind it.
METHODS AND RESULTS
IGFBP5 expression was elevated in the vascular endothelium of gastrocnemius muscle from critical limb ischaemia patients and hindlimb ischaemic (HLI) mice and hypoxic human umbilical vein endothelial cells (HUVECs). In vivo, loss of endothelial IGFBP5 (IGFBP5) facilitated the recovery of blood vessel function and limb necrosis in HLI mice. Moreover, skin damage healing and aortic ring sprouting were faster in IGFBP5 mice than in control mice. In vitro, the genetic inhibition of IGFBP5 in HUVECs significantly promoted tube formation, cell proliferation and migration by mediating the phosphorylation of IGF1R, Erk1/2 and Akt. Intriguingly, pharmacological treatment of HUVECs with recombinant human IGFBP5 ensued a contrasting effect on angiogenesis by inhibiting the IGF1 or IGF2 function. Genetic inhibition of IGFBP5 promoted cellular oxygen consumption and extracellular acidification rates via IGF1R-mediated glycolytic adenosine triphosphate (ATP) metabolism. Mechanistically, IGFBP5 exerted its role via E3 ubiquitin ligase Von Hippel-Lindau (VHL)-regulated HIF1α stability. Furthermore, the knockdown of the endothelial IGF1R partially abolished the reformative effect of IGFBP5 mice post-HLI.
CONCLUSION
Our findings demonstrate that IGFBP5 ablation enhances angiogenesis by promoting ATP metabolism and stabilising HIF1α, implying IGFBP5 is a novel therapeutic target for treating abnormal angiogenesis-related conditions.
Topics: Animals; Insulin-Like Growth Factor Binding Protein 5; Mice; Hindlimb; Humans; Human Umbilical Vein Endothelial Cells; Ischemia; Disease Models, Animal; Male; Neovascularization, Physiologic; Angiogenesis
PubMed: 38886900
DOI: 10.1002/ctm2.1725