Thromboangiitis Obliterans Research Articles

Peripheral Ischemia and Necrosis Revealing Buerger's Disease in an Internal Medicine Department

Buerger's disease is a systemic vasculitis strongly correlated with tobacco use. It entails a heavy socio-occupational impact. We report the case of a 26-year-old patient with ischemia of the lower limbs revealing Buerger’s disease. He is known smoker with passive exposure to Indian hemp. He was seen for ischemic foot pain that had been progressing for a year. Involvement began in the left big toe. Subsequently, hyperalgesic necrotic lesions were observed on the 3rd, 4th and 5th toes of the foot. Biological investigations revealed an inflammatory syndrome with normocytic anemia and increased C-reactive protein. Retroviral, syphilitic, Hepatitis B and C viruses and SARS-CoV-2 serologies were negative. Antinuclear antibodies were initially borderline at 100 IU with speckled fluorescence, then negative on control. Neutrophil cytoplasmic antibodies and antiphospholipid antibodies were negative. Investigation of thrombophilia was non-contributory, notably factor V mutation testing, antithrombin III assay, proteins C and S and fibrinogen. An arterial ultrasound revealed extensive arterial thrombosis with thickening of the femoral arterial vessel walls. Thromboangiitis obliterans was confirmed and the patient was put on corticosteroids and adjuvant therapy. Surgical treatment was performed 4 months later. Buerger's disease is a serious vascular disorder which must be diagnosed very early in order to prevent complications. Early smoking cessation leads to remission in the early phase.

Preliminary application of ulnar cortex transverse transport technique in treatment of upper extremity thromboangiitis obliterans

To investigate the feasibility and effectiveness of ulnar cortex transverse transport technique in treating upper extremity thromboangiitis obliterans (TAO). A retrospective analysis was conducted on the clinical data of 7 male patients with upper extremity TAO who were admitted and met the inclusion criteria between January 2019 and July 2022. The patients ranged in age from 32 to 50 years, with a mean age of 40.1 years. The disease duration ranged from 6 to 24 months, averaging 13.6 months. The smoking history ranged from 8 to 31 years, with a mean of 18.4 years. All patients presented with finger ulcers or gangrene, including 1 case affecting the thumb and index finger, 1 case affecting the index and middle fingers, 1 case affecting the middle and ring fingers, 1 case affecting only the ring finger, and 3 cases affecting the ring and little fingers. The preoperative visual analogue scale (VAS) score was 9.1±0.7. All patients underwent treatment with the ulnar cortext transverse transport technique. The wound healing time and the disappearance time of rest pain were recorded. The VAS score was used to assess the degree of hand pain before and after operation. Serum interleukin 6 (IL-6) levels were measured before operation and at 1 month after operation. Computed tomography angiography (CTA) of the affected limb was performed before operation and at 3 months after operation to evaluate changes in blood vessels. The clinical outcomes were evaluated at 1 year after operation based on the Patwa and Krishnan grading system. All 7 patients were followed up 12-17 months, with an average of 13.7 months. All patients experienced successful healing of ulcers, with wound healing time ranging from 14 to 21 days, averaging 17.3 days. During the follow-up, no complication occurred, and there was no recurrence of ulcers. The disappearance time of rest pain ranged from 8 to 15 days, averaging 12.1 days. The pre- and post-operative (1-month) serum IL-6 levels were (25.1±5.9) pg/mL and (11.9±2.9) pg/mL, respectively, with a significant difference ( t=5.363, P=0.002). CTA examination at 3 months after operation revealed partial revascularization of upper extremity arteries and establishment of collateral circulation, showing significant improvement compared to preoperative status. The VAS scores at 1, 7, 28 days, and 6 months postoperatively were 6.4±0.8, 3.7±0.8, 0.6±0.8, and 0.1±0.4, respectively, all of which significantly improved compared to preoperative scores ( P<0.05). Furthermore, the VAS scores gradually decreased over time, with significant differences observed between postoperative time points ( P<0.05). At 1 year after operation, the effectiveness of all 7 patients were evaluated as excellent based on the Patwa and Krishnan grading system. The ulnar cortex transverse transport technique can improve blood circulation in the upper limb of patients with TAO, reconstruct microcirculation, inhibit inflammation, promote ulcer healing, and alleviate limb pain.

Rare clinical presentations and advances in the treatment of Buerger's disease - narrative review

Rare clinical presentations and advances in the treatment of Buerger's disease - narrative review

Mesenchymal stromal cell therapy (REGENACIP®), a promising treatment option in chronic limb threatening ischemia - a narrative review.

Chronic Limb Threatening Ischemia (CLTI) is a challenging clinical problem associated with high morbidity and mortality. Endovascular interventions have been the cornerstone of treatment whenever possible. It is estimated that CLTI represents < 10% of all Peripheral Artery Disease patients, yet 50% of the patients end up either with a major amputation of the lower limbs or die of cardiovascular causes within one year period, especially in those with unsuccessful revascularization or "no-option" CLTI. Cell-based therapeutics, especially bone marrow-derived mesenchymal stromal cells have emerged as a potential, promising, and novel alternate therapeutic modality in the management of CLTI, bolstered with positive results in numerous research, including randomized and nonrandomized trials. REGENACIP® is one such BM-MSC therapy approved by Central Drugs Standard Control Organization in India for the management of "no-option" Atherosclerotic Peripheral Arterial disease / Buerger's disease patients with established critical limb ischemia in Rutherford Grade III-5 or III-6, not eligible for or have failed traditional revascularization treatment, with rest pain and / or ulcers in the affected limb. The current review aims to deliberate upon the various aspects of CLTI and clinical benefits of REGENACIP® therein.

Purified CD34+ Cells Transplantation in Patients with Angiitis-induced Chronic Limb-threatening Ischemia: A Single-center Retrospective Study over A 10-year Period

Angiitis-induced chronic limb-threatening ischemia (AICLTI) is defined as chronic limb-threatening ischemia (CLTI) caused by thromboangiitis obliterans (TAO) or other arteritis-related autoimmunological diseases. In the current study, we aimed to report the 10-year outcomes of AICLTI patients who underwent purified CD34+ cells (PCCs) transplantation. AICLTI patients who underwent PCCs transplantation at our center from May 2009 to September 2011 were retrospectively enrolled. The main outcome was major amputation-free survival (MAFS); other outcomes included Rutherford classification, intolerable pain-free walking time (IPFWT), Wong-Baker Faces Pain Rating Scale (WBFPS), recurrence, new lesions, quality of life (QoL) and patients' posttransplantation work conditions. Twenty-four patients were enrolled with a mean age of 41.5±7.8 years. Three underwent major amputation during the follow-up, and the 10-year MAFS was 87.5%. Eight were observed to have recurrence, and 2 had new lesions; the 10-year recurrence-free rate was 66.1%. All patients were unable to work at admission, 17 (70.8%) patients were reemployed after transplantation. The current study further demonstrated satisfactory long-term efficacy of PCCs transplantation, with a 10-year MAFS of 87.5%. However, the 10-year recurrence-free rate of 66.1% suggested that strict and regular long-term follow-up is necessary.

Factors effecting the success of retrograde tibiopedal access and recanalization in infrapopliteal artery occlusions.

Peripheral arterial disease (PAD) is increasingly prevalent, particularly among the aging population. Retrograde tibiopedal access (RTPA) has emerged as a useful endovascular treatment for PAD. However, there is limited research examining factors that influence the efficacy of RTPA. To investigate factors affecting the access, crossing, and recanalization success rates of RTPA for infrapopliteal PAD treatment. A retrospective study was conducted on 720 patients who underwent endovascular treatment for PAD. Of these, 104 patients (mean age: 65.5 ± 16.2; 89 men) with 131 RTPA trials were included in the final evaluation. The disease and its duration, Rutherford score, smoking status, access site, and its occlusion status, access, crossing, and recanalization success were noted. Data were analyzed using Pearson's chi-square and Mann-Whitney U tests and multivariate logistic regression to evaluate the impact of various factors on success rates. The access success rate was 82.6%, the crossing success rate was 95.4%, and the recanalization success rate was 74%. Access success was significantly higher when the dorsal pedal artery (DPA) was the access artery compared with the posterior tibial artery (91.3% vs. 74.2%, P = 0.009). Access success was notably lower in patients with thromboangiitis obliterans compared with patients with diabetes mellitus (DM) and non-DM atherosclerosis (68.6% vs. 90.3% and 80.3%, P = 0.019). Recanalization success was higher when the puncture site was non-occluded (76.7% vs. 53.5%, P = 0.023). The study suggests that RTPA is a generally effective and safe technique for infrapopliteal PAD treatment. The most favorable outcomes are observed in individuals with DM who have a non-occluded DPA at the puncture site. Recanalization success is only affected by the patency of the artery at the puncture site. These findings offer targeted guidance for clinicians and highlight areas requiring further investigation.

Current Diagnostic and Therapeutic Challenges in Superficial Venous Thrombosis.

Superficial venous thrombosis (SVT) is a fairly common disorder, characterized by the formation of thrombi inside superficial veins, with or without an associated inflammatory reaction. Its evolution is frequently self-limited. However, serious complications may change this clinical course with extension to deep vein thrombosis (DVT) and pulmonary embolism (PE). SVT shares similar risk factors with DVT and is frequently associated with the presence of varicose veins. However, the occurrence of non-varicose veins could conceal risk factors such as malignancies, thrombophilia, or Buerger's disease. While the clinical diagnosis is generally straightforward, additional diagnostic evaluations are often necessary. Duplex ultrasound (DUS) is an invaluable tool that provides the location of SVT, the proximity to the sapheno-femoral junction, and the clot length, all of which influence the decision for optimal management. The treatment of SVT should be symptomatic, pathogenic (limiting the extension of thrombosis), and prognostic (to prevent complications). There are several guidelines that provide recommendations, and despite the need for more consensus and for further studies, the treatment of SVT should be mainly medical, including anticoagulation in specific clinical situations and symptom relief, with invasive treatment in a minority of cases. Initiation, intensity, and length of anticoagulant treatment should be based on the eventual risk of progression to DVT or PE, which can be high, intermediate, or low, based on the location of SVT and the clot length. Our review summarizes the evaluation and proper management of SVT and highlights the importance of a shared decision within the heart team regarding this condition in order to prevent further complications.

Elevation and distraction of the Tibial periosteum in the management of chronic ischemic lower limb diseases.

This study investigates the effectiveness of tibia periosteum distraction (TPD) applied to the tibial periosteum, an innovative approach grounded in Ilizarov's tension-stress theory, for the treatment of ischemic diabetic foot and vasculitic foot conditions. A retrospective analysis was conducted on 33 patients (36 limbs) who underwent TPD between June 2019 and May 2022. The study comprised 21 males (23 limbs) and 12 females (13 limbs), aged 41 to 80 years (mean age: 63.4 years). Diabetic foot accounted for 27 cases, thromboangiitis obliterans for 2 cases, and arterial occlusive disease for 4 cases. The distribution of affected limbs included 15 left feet and 21 right feet. Periosteum traction commenced on the third postoperative day at a rate of approximately 0.75mm/day, adjusted biweekly. The traction device was removed after two weeks. Evaluation included capillary refill and wound healing assessment, along with pre- and postoperative analysis of foot skin temperature, ankle-brachial index (ABI), visual analogue scale (VAS) pain scores, and peripheral blood oxygen saturation. CT angiography (CTA) was utilized to assess vascular conditions in both lower limbs. All 33 patients were successfully followed up for a duration ranging from 4 to 24 weeks (mean: 11.03 weeks). VAS pain scores significantly decreased from preoperative (5.09 ± 1.70, range: 2-8) to postoperative two weeks (2.24 ± 0.90, range: 1-4) (t = 9.44, p < .001). Oxygen saturation levels increased from 83.88% ± 11.82% (range: 58%-97%) preoperatively to 91.36% ± 5.69% (range: 76%-98%) at two weeks postoperatively (t = -4.21, p < .001). Foot skin temperature also showed a significant increase (t = -3.98, p < .001). Capillary refill test at two weeks postoperatively demonstrated notable improvement. CTA revealed evident neovascularization in the operated limbs compared to preoperative conditions. Wound improvement was significant in all 33 patients within two months postoperatively. TPD emerges as a promising technique for chronic ischemic lower limb diseases, demonstrating favorable preliminary outcomes in wound healing promotion and amputation rate reduction. Nevertheless, large-scale randomized controlled trials are essential to further validate its efficacy.

Mailuoning oral liquid ameliorates vasculitis in thromboangiitis obliterans rats via inactivating cGAS-STING-IRF3 and TLR4-MAPKs/NF-κB signaling pathways

Ethnopharmacological relevanceMailuoning oral liquid (MLN O), one traditional Chinese patent medicine, has a good therapeutic effect on thromboangiitis obliterans (TAO) in clinical practice. However, the underlying mechanism remains unclear. Aim of the studyThis study aimed to explore the effects and potential mechanisms of MLN O against TAO based on network pharmacology and experimental verification. Materials and methodsNetwork pharmacology was used to identify the intersectional targets and signaling pathways of MLN O and TAO. In vivo, the TAO model was established by injecting sodium laurate and dihydrotestosterone (DHT) into the femoral arteries of Wistar rats. Rats were given the indicated drugs by intragastric administration (i.g.), intravenous injection (i.v.), or subcutaneous injection (s.c.) per day for 21 days since a week before surgery. In vitro, HUVECs, RAW264.7, and THP-1 cells were stimulated by LPS and DHT to simulate the pathological changes of TAO. The anti-inflammatory, anticoagulant, and immunomodulatory effects of MLN O were evaluated by histological observation, blood biochemical indexes detection, H&E staining, immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), qRT-PCR, western blotting and immunofluorescence assays. Furthermore, the vascular ring test was applied to explore the vasodilatory activity of MLN O. ResultsMLN O significantly improved the pathological signs in TAO rats through its excellent anti-inflammatory, anticoagulant, immunomodulatory, and vasodilatory effects. Specifically, MLN O alleviated the gangrene and reduced the thrombosis in TAO rats, meanwhile, suppressed the expressions of inflammatory factors and clotting factors, which is related to the inactivations of cGAS-STING-IRF3 and TLR4-MAPKs/NF-κB signaling pathways. However, the superphysiological dose of DHT deteriorated the pathological development of TAO in vitro and in vivo. Moreover, the results of network pharmacology are consistent with the experimental verification. ConclusionCollectively, this study indicates for the first time that MLN O could alleviate TAO by inhibiting cGAS-STING-IRF3 and TLR4-MAPKs/NF-κB signaling pathways, which sheds light on a novel clinical therapeutic strategy for TAO.

A case of Buerger's disease with vasculopathy and skin fibrosis requiring differential diagnosis from systemic sclerosis.

Buerger's disease is characterized by peripheral ischemia due to occlusion of small- and medium-sized arteries in the extremities. This report describes a case of Buerger's disease in a 51-year-old male who presented with findings resembling systemic sclerosis. The patient exhibited Raynaud's phenomenon in year X-3, which developed to skin hardening, nail avulsion, and ulceration of the right fingers in year X. Diagnostic testing showed positive microvasculopathy on nailfold videocapillaroscopy (NVC) and positive fibrosis on skin biopsy. Although the patient fulfilled the 2013 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for systemic sclerosis, several findings in this case were atypical for systemic sclerosis, including left-right asymmetry in finger involvement, nail loss, and negative autoantibody tests. Contrast-enhanced computed tomography showed poor perfusion of the right ulnar artery, and a heavy smoking history was established in the patient case. Therefore, based on Shionoya's criteria, he was diagnosed with a case of Buerger's disease confined to the upper extremity. Smoking cessation and vasodilator therapy resulted in the prompt resolution of ischemic symptoms, skin hardening, and ulcerations. Furthermore, NVC abnormalities improved, and ulnar artery occlusion showed reperfusion on repeat testing. The present case suggests that hypoxemia-driven microvasculopathy may contribute to vascular occlusion and skin fibrosis observed in this atypical presentation.

Intra-Arterial Nitroglycerin Injection in Upper Extremity Buerger's Disease for Faster Ulcer Recovery: A Case Report

AbstractThromboangiitis obliterans (TAO), also known as Buerger's disease, is a challenging nonatherosclerotic vascular disorder predominantly affecting smokers. Current management of TAO lacks standard guidelines, with smoking cessation as the only cornerstone. We present the case of a 28-year-old smoker with TAO manifesting as necrotic finger ulcers. Regardless of initial debridement, conventional therapy failed to improve his condition. Angiography confirmed the diagnosis of TAO and intra-arterial nitroglycerin injection was administered, leading to immediate vasodilation and improved perfusion. Combined with oral vasodilators and anticoagulants, the patient showed significant ulcer healing within 2 weeks. TAO's etiology remains unclear; however, it is linked to smoking and immune responses. Diagnosis relies on clinical criteria and angiographic findings. While smoking cessation remains crucial, various pharmacological interventions like vasodilators show considerable potential for enhancing therapeutic outcomes. Our case highlights the potential of intra-arterial nitroglycerin in TAO management. However, further studies are warranted due to limited sample size. Advancements in understanding TAO's biology and diagnostic techniques offer hope for improved management strategies in the future.

Gene Therapy of Thromboangiitis Obliterans with Growth Factor Plasmid (VEGF165) and Autologous Bone Marrow Cells.

We performed gene therapy for critical limb ischemia in thromboangiitis obliterans (TAO) by the intramuscular administration of plasmids of the vascular endothelial growth factor gene (VEGF 165) with or without bone marrow-derived stem cells. The 21 patients were randomly assigned to three groups: A-with dual therapy, cells and plasmid; B-plasmid only; and C-control group, where patients received intramuscular injections of saline. Serum VEGF levels, the ankle-brachial index (ABI), transcutaneous oxygen pressure (TcPO2), and the rest pain measured by the visual analog scale (VAS) were determined sequentially before treatment, and then 1 and 3 months after treatment. In the treatment groups, serum VEGF levels increased by 4 weeks and returned to baseline values after 3 months. ABI after 12 weeks increased by an average of 0.18 in group A, and 0.09 in group B and group C. TcPO2 increased by an average of 17.3 mmHg in group A, 14.1 mmHg in group B, and 10.7 mmHg in group C. The largest pain decrease was observed in group A and averaged 5.43 less pain intensity. Gene therapy using the VEGF plasmid along with or without bone marrow-derived mononuclear cells administered intramuscularly into an ischemic limb in TAO is a safe and effective therapy.

The Role of Gut Microbiota in Thromboangiitis Obliterans: Cohort and Mendelian Randomization Study.

Thromboangiitis obliterans (TAO), also known as Buerger's disease, is a rare vasculitis. Observational epidemiology studies have suggested a relationship between the gut microbiota and TAO. However, due to confounding factors and reverse causality, the causal relationship remains unclear. Based on the assumption of their association, this study sought specific gut microbiota causally linked to TAO. The case-control study was conducted at the Xiangya Hospital of Central South University from November 2022 to January 2023 including twelve TAO patients and nine healthy controls. We conducted a Mendelian randomization (MR) study using summary statistics from a genome-wide association study (GWAS) of gut microbiota and TAO. Considering the scale and accessibility of the data, the MiBioGen consortium served as the exposure, whereas the FinnGen consortium GWAS study served as the outcome. Finally, we compared the results of the MR with those of the case-control studies. The inverse variance weighted (IVW) (OR = 0.119, 95% CI: 0.021-0.688, p = 0.017) and maximum likelihood (ML) (OR = 0.121, 95% CI: 0.020-0.742, p = 0.022) estimates suggest that Ruminiclostridium 5 has a suggestive protective effect on TAO while the IVW (OR = 5.383, 95% CI: 1.128-25.693, p = 0.035) and ML (OR = 5.658, 95% CI: 1.142-28.021, p = 0.034) estimates suggest that Eubacterium (xylanophilum group) has a suggestive risk effect on TAO, and the ML (OR = 0.055, 95% CI: 0.004-0.755, p = 0.030) estimates suggest that Lachnospira has a suggestive protective effect on TAO. No significant heterogeneity of instrumental variables or horizontal pleiotropy was found. The results of the case-control study showed that the TAO had a lower relative abundance of Ruminiclostridium 5 (p = 0.015) and Lachnospira (p = 0.048), and a higher relative abundance of Eubacterium (xylanophilum group) (p = 0.029) than the healthy controls. These results were consistent with the MR analysis. Our study demonstrates that Ruminiclostridium 5, Lachnospira, and Eubacterium (xylanophilum group) are causally related to TAO, suggesting their potential significance for the prevention and treatment of TAO.

Gangrenous manifestation of thromboangiitis obliterans (Buerger’s disease) in a chronic smoker: A case report

Gangrenous manifestation of thromboangiitis obliterans (Buerger’s disease) in a chronic smoker: A case report

Short-term efficacy of endovascular procedures for lower extremity thromboangiitis obliterans (Buerger’s disease)

ABSTRACT Purpose Although thrombolysis obliterans (TAO) has been recognized for more than a century, there is no optimal treatment for this disease. The aim of this report was to compare the short-term efficacies of catheter-directed thrombolysis (CDT), percutaneous transluminal angioplasty (PTA) and CDT+PTA in treating TAO disease. Method Consecutive patients with TAO treated at Ganzhou People’s Hospital between 2012 and 2022 were included in this retrospective study. According to the information provided in the medical records, endovascular procedures included CDT, PTA or CDT+PTA. One-year follow-up outcomes of the patients with TAO who underwent endovascular procedures were compared. The primary outcome was major adverse limb event (MALE) and the secondary outcomes were the technical success, complications, ABI at 1 week after surgery and minor amputation. Results Sixty-nine patients with TAO were assessed for inclusion in our single-center study from 2012 to 2022 and received endovascular procedures. Among them, 22 patients underwent CDT, 21 patients underwent PTA, and 26 patients underwent PTA+CDT. The one-year follow-up revealed significant differences in the MALE-free survival rates among the three groups, particularly between the CDT group and the PTA+CDT group (the hazard ratio (HR) for MALE-free survival was 0.173, 95% CI [0.050–0.599], p = 0.006). The technical success rates of the three groups were 63.6%, 90.5%, and 92.3%, respectively. There were differences in the ABI at one week after surgery among the three groups. Conclusions Endovascular procedures are effective for TAO in the short term. The effectiveness of CDT alone is suboptimal; combining CDT with PTA achieves the most favorable endovascular treatment outcome; while the effectiveness of PTA falls in between these two procedures.

Low-intensity pulsed ultrasound improves symptoms in patients with Buerger disease: a double-blinded, randomized, and placebo-controlled study

Here we report the effects of low-intensity pulsed ultrasound (LIPUS) on symptoms in peripheral arterial disease patients with Buerger disease. A double-blinded and randomized study with active and inactive LIPUS was conducted. We assessed symptoms in leg circulation during a 24-week period of LIPUS irradiation in 12 patients with Buerger disease. Twelve patients without LIPUS irradiation served as controls. The pain intensity on visual analog score was significantly decreased after 24-week LIPUS treatment. Skin perfusion pressure was significantly increased in patients who received LIPUS treatment. There was no significant difference in symptoms and perfusion parameters in the control group. No severe adverse effects were observed in any of the patients who underwent LIPUS treatment. LIPUS is noninvasive, safe and effective option for improving symptoms in patients with Buerger disease.

Isolated visceral manifestation of Buerger’s disease presenting as intestinal obstruction: a case report

Introduction and importance: Buerger’s disease is an uncommon segmental nonatherosclerotic vasculitis essentially affecting small to medium-sized arteries and veins of upper and lower extremities and can lead to limb amputation. Visceral vessel involvement is quite rare accounting for 2% of cases presenting with acute abdomen due to mesenteric ischemia. Moreover, isolated visceral involvement is even rare. Case presentation: A 42-year-old gentleman, a chronic smoker, presented with abdominal pain associated with nausea and vomiting and loose stool of 2 months duration. Magnetic resonance enterography revealed segmental circumferential wall thickening with stricture in the mid part of the jejunum with lymphadenopathy features of possible inflammatory bowel disease (Crohn’s disease). Furthermore, intraoperative surgical findings were also suggestive of Crohn’s disease. However, histologic findings were consistent with thromboangiitis obliterans. Discussion: Thromboangiitis obliterans can present with inflammatory vascular lesions without necrosis in the early stage to varying degrees of recanalisation, gangrene, and amputation in the late stage. It rarely involves the brain, heart, and abdominal viscera. The visceral involvement may be in the form of intestinal obstruction or mesenteric ischemia or can mimic Crohn’s in a background of smoking. Conclusion: This case report will help to learn more about the rarer intestinal presentation of intestinal Buerger’s disease. It can present with features of bowel ischemia, obstruction or Crohn’s. So, histology would play a pivotal role in differentiating the diagnostic dilemma.

Vasoactive and Antifibrotic Properties of Cannabinoids and Applications to Vasospastic/Vaso-Occlusive Disorders

Background Management of vasospastic and vaso-occlusive disorders is a complex challenge, with current treatments showing varied success. Cannabinoids have demonstrated both vasodilatory and antifibrotic properties, which present potential mechanisms for therapeutic relief. No existing review examines these effects in peripheral circulation in relation to vasospastic and vaso-occlusive disorders. This study aims to investigate vasodilatory and antifibrotic properties of cannabinoids in peripheral vasculature for application in vasospastic and vaso-occlusive disorders affecting the hand. Methods A systematic search was conducted by 2 independent reviewers across PubMed, Cochrane, Ovid MEDLINE, and CINAHL to identify studies in accordance with the determined inclusion/exclusion criteria. Information regarding study design, medication, dosage, and hemodynamic or antifibrotic effects were extracted. Descriptive statistics were used to summarize study findings as appropriate. Results A total of 584 articles were identified, and 32 were selected for inclusion. Studies were grouped by effect type: hemodynamic (n = 17, 53%) and antifibrotic (n = 15, 47%). Vasodilatory effects including reduced perfusion pressure, increased functional capillary density, inhibition of vessel contraction, and increased blood flow were reported in 82% of studies. Antifibrotic effects including reduced dermal thickening, reduced collagen synthesis, and reduced fibroblast migration were reported in 100% of studies. Conclusion Overall, cannabinoids were found to have vasodilatory and antifibrotic effects on peripheral circulation via both endothelium-dependent and independent mechanisms. Our review suggests the applicability of cannabis-based medicines for vasospastic and vaso-occlusive disorders affecting the hand (eg, Raynaud disease, Buerger disease). Future research should aim to assess the effectiveness of cannabis-based medicines for these conditions.

Exploring Causal Relationships between Circulating Inflammatory Proteins and Thromboangiitis Obliterans: A Mendelian Randomization Study.

Thromboangiitis obliterans (TAO) is a vascular condition characterized by poor prognosis and an unclear etiology. This study employs Mendelian randomization (MR) to investigate the causal impact of circulating inflammatory proteins on TAO. In this MR analysis, summary statistics from a genome-wide association study meta-analysis of 91 inflammation-related proteins were integrated with independently sourced TAO data from the FinnGen consortium's R10 release. Methods such as inverse variance weighting, MR-Egger regression, weighted median approaches, MR-PRESSO, and multivariable MR (MVMR) analysis were utilized. The analysis indicated an association between higher levels of C-C motif chemokine 4 and a reduced risk of TAO, with an odds ratio (OR) of 0.44 (95% confidence interval [CI]: 0.29-0.67; p = 1.4 × 10-4; adjusted p = 0.013). Similarly, glial cell line-derived neurotrophic factor exhibited a suggestively protective effect against TAO (OR: 0.43, 95% CI: 0.22-0.81; p = 0.010; adjusted p = 0.218). Conversely, higher levels of C-C motif chemokine 23 were suggestively linked to an increased risk of TAO (OR: 1.88, 95% CI: 1.21-2.93; p = 0.005; adjusted p = 0.218). The sensitivity analysis and MVMR revealed no evidence of heterogeneity or pleiotropy. This study identifies C-C motif chemokine 4 and glial cell line-derived neurotrophic factor as potential protective biomarkers for TAO, whereas C-C motif chemokine 23 emerges as a suggestive risk marker. These findings elucidate potential causal relationships and highlight the significance of these proteins in the pathogenesis and prospective therapeutic strategies for TAO.

Integrated network pharmacology and metabolomics reveal vascular protective effects of Ilex pubescens on thromboangiitis obliterans

BackgroundIlex pubescens Hook. et Arn (IP), traditionally known for its properties of promoting blood circulation, swelling and pain relief, heat clearing, and detoxification, has been used in the treatment of thromboangiitis obliterans (TAO). Despite its traditional applications, the specific mechanisms by which IP exerts its therapeutic effects on TAO remain unclear. Aim of the studyThis study aims to uncover the underlying mechanisms in the therapeutic effects of IP on TAO, employing network pharmacology and metabolomic approaches. MethodsIn this study, a rat TAO model was established by injecting sodium laurate through the femoral artery, followed by the oral administration of IP for 7 days. Plasma coagulation parameters were measured to assess the therapeutic effects of IP. The potential influence on the femoral artery and gastrocnemius muscle was histopathologically evaluated. Network pharmacology was employed to predict relevant targets and model pathways for TAO. Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS) was used for the metabolic profile analysis of rat plasma. Immunohistochemistry (IHC) was used to verify the mechanisms by which IP promotes blood circulation in TAO. ResultsThe study revealed that IP improved blood biochemical function in TAO and played a significant role in vascular protection and maintaining normal blood vessels and gastrocnemius morphologies. Network pharmacology showed that IP compounds play a therapeutic role in modulating lipids and atherosclerosis. Metabolomic analysis revealed that the pathways involved in sphingolipid metabolism and steroid biosynthesis were significantly disrupted. The joint analysis showed a strong correlation between lysophosphatidylcholine and IP components, including triterpenoid and iridoid components, which support the curative action of IP through the modulation of sphingolipid metabolism. Furthermore, decreased expression levels of SPHK1/S1PR1, TNF-α, IL-1β, and IL-6 were observed in the IP-treated group, suggesting that IP exerts a protective effect on the vasculature primarily by regulating of the SPHK1/S1PR1 signaling pathway. ConclusionIn this study, we found that IP protects the vasculature against injury and treats TAO by regulating the steady-state disturbance of the sphingolipid pathway. These findings suggest that IP promotes vasculature by modulating sphingolipid metabolism and SPHK1/S1PR1 signaling pathway and reduce levels of inflammatory factors, offering new insights into its therapeutic potential.