1,721,032 research outputs found
New therapeutic effects of cilostazol in patients with ischemic disorders.
No full textCilostazol (CIL) is effective for the treatment of patients with peripheral arterial disease (PAD). CIL is an orally administered drug with multiple effects, including anti-platelets aggregation, favorable functions on plasmatic lipids and vasodilator ones, but how these effects might be related to improvement in patients walking affected by PAD is not fully understood. The latest data demonstrate that nitric oxide (NO) is induced by CIL through endothelial nitric oxide synthase (eNOS) activation via a cyclic-AMP (cAMP)/ protein kinase A (PKA)- and PI3K/Akt- dependent mechanism. This mechanism is also responsible for the vasodilatation dependent on endothelium which characterized patients receiving CIL. Other investigators have found that CIL notably reduces the exercise-induced host-inflammatory response in PAD patients, and consequently it improves lipid hydroperoxides and cell-adhesion molecule levels. We recently reported that CIL is able to cause neoangiogenesis in vivo by stimulating the production of proangiogenic proteins, such as vascular endothelial growth factor (VEGF), that increase levels of Endothelial progenitor cells (EPCs) and the formation of new blood vessels. The mechanisms of action of this drug are several and are not clear and established. The objective of the present review is to analyze the existing data about the therapeutic effects of CIL, with the purpose of providing practical indications about this topic for the management of subjects affected by ischemic disorders
Therapeutic potential of high mobility group box-1 in ischemic injury and tissue regeneration.
No full textHigh-mobility group box-1 (HMGB1) is a nuclear protein that acts as a cytokine when released into the extracellular milieu by necrotic and inflammatory cells, and is involved in inflammatory responses and tissue repair. This protein is released passively during cellular necrosis by almost all cells that have a nucleus, but is also actively secreted by immune cells such as macrophages and monocytes. This cytokine plays a key role in mediating the local and systemic responses to several stimuli and might have therapeutic relevance. Indeed, vessel-associated stem cells, injected into the general circulation of dystrophic mice, migrate to sites of tissue damage in response to the HMGB1 signal, by a nuclear factor-κB dependent mechanism. Moreover, endogenous HMGB1 enhances angiogenesis and restores cardiac function in a murine model of myocardial infarction, and the exogenous administration of HMGB1 after myocardial infarction leads to the recovery of left ventricular function through the regeneration of cardiomyocytes. Finally, recent findings show that endogenous HMGB1 is crucial for ischemia-induced angiogenesis in diabetic mice and that HMGB1 protein administration enhances collateral blood flow in the ischemic hind limbs of diabetic mice through a VEGF-dependent manner. The mechanisms of action of this protein are complex and are not well known or defined. The objective of this review is to evaluate the data regarding the tissue regeneration effects of HMGB1, with the aim of providing practical considerations about this topic for the management of subjects affected by ischemic and degenerative diseases
Analysis of completion intraoperative venography during first rib resection for venous thoracic outlet syndrome
No full textBackground: We evaluated the impact of completion intraoperative venography on clinical outcomes for axillosubclavian vein (AxSCV) thrombosis owing to venous thoracic outlet syndrome (vTOS). Methods: We performed a retrospective, single-center review of all patients with vTOS treated with first rib resection (FRR) and intraoperative venography from 2011 to 2023. We reviewed intraoperative venographic films to classify findings and collected demographics, clinical and perioperative variables, and clinical outcomes. Primary end points were symptomatic relief and primary patency at 3 months and 1 year. Secondary end points were time free from symptoms, reintervention rate, perioperative complications, and mortality. Results: Fifty-one AxSCVs (49 patients; mean age, 31.3 ± 12.6 years; 52.9% female) were treated for vTOS with FRR and external venolysis followed by completion intraoperative venography with a mean follow up of 15.5 ± 13.5 months. Before FRR, 32 underwent catheter-directed thrombolysis (62.7%). Completion intraoperative venography identified 16 patients with no stenosis (group 1, 31.3%), 17 with no stenosis after angioplasty (group 2, 33.3%), 10 with residual stenosis after angioplasty (group 3, 19.7%), and 8 with complete occlusion (group 4, 15.7%). The overall symptomatic relief was 44 of 51 (86.3%) and did not differ between venographic classifications (group 1, 14 of 16; group 2, 13 of 17; group 3, 10 of 10; and group 4, 7 of 8; log-rank test, P = .5). The overall 3-month and 1-year primary patency was 42 of 43 (97.7%) and 32 of 33 (97.0%), respectively (group 1, 16 of 16 and 9 of 9; group 2, 16 of 17 and 12 of 13; group 3, 10 of 10, 5 of 5; group 4, primary patency not obtained). There was one asymptomatic rethrombosis that resolved with anticoagulation, and three patients underwent reintervention with venous angioplasty for significant symptom recurrence an average 2.89 ± 1.7 months after FRR. Conclusions: Our single-center retrospective study demonstrates that FRR with completion intraoperative venography has excellent symptomatic relief and short- and mid-term patency despite residual venous stenosis and complete occlusion. Although completion intraoperative venographic classification did not correlate with adverse outcomes, this protocol yielded excellent results and provides important clinical data for postoperative management. Our results also support a conservative approach to AxSCV occlusion identified after FRR
Association of Klotho and FGF23 with cardiovascular outcomes in diabetic older adults with chronic limb-threatening ischemia: a prospective study
No full textPeripheral arterial disease (PAD) is more prevalent in individuals with type 2 diabetes mellitus (T2DM). The most severe complication of PAD is chronic limb-threatening ischemia (CLTI), which is associated with major adverse cardiovascular events (MACE) and major adverse limb events (MALE) following lower limb revascularization (LER). This study investigates the relationship between baseline levels of Klotho and FGF23 and the risk of cardiovascular and limb-related outcomes after LER in a selected cohort of older adults. The study enrolled 109 older patients with PAD and CLTI requiring LER. Baseline levels of Klotho and FGF23 were measured, and their associations with subsequent MACE and MALE were analyzed over a 12-month follow-up period. Using stepwise multivariable logistic regression and Cox proportional hazards models, we found that among 109 older patients with PAD and CLTI undergoing LER, independent predictors of MACE included age (p = 0.016), male sex (p = 0.006), BMI (p = 0.004), diabetes duration (p = 0.031), hypertension (p = 0.013), and smoking status (p < 0.001), with higher FGF23 (p < 0.001) and lower Klotho levels (p = 0.002) significantly associated with increased risk; in the Cox model, increased Klotho was linked to a reduced risk of MACE (95% CI: 0.994–1.000, p = 0.022), while multivariate analysis for MALE confirmed Klotho as an independent predictor (p < 0.01). These findings reinforce the hypothesis that altered baseline levels of Klotho, and FGF23 are associated with adverse cardiovascular and limb outcomes in diabetic individuals over 75 years old with PAD and CLTI, highlighting their potential role as biomarkers for post-revascularization risk stratification
Association between TNFRSF11B gene polymorphisms and history of ischemic stroke in Italian diabetic patients.
No full textOsteoprotegerin (OPG) is a secretory glycoprotein that belongs to the tumor necrosis factor receptor family and plays a role in atherosclerosis. The present study aimed to evaluate whether OPG gene (TNFRSF11B) polymorphisms are involved in ischemic stroke in an Italian population with diabetes. Participants in a retrospective case-control study included 364 diabetic patients (180 males, 184 females) with history of ischemic stroke and 492 diabetic subjects without history of ischemic stroke (252 males, 240 females). The T245G, T950C, and G1181C polymorphisms of the OPG gene were analyzed by polymerase chain reaction and restriction fragment length polymorphism. We found that the T245G, T950C, and G1181C gene polymorphisms of the OPG gene were significantly (34.1 vs. 9.5 %, P < 0.0001; 30.8 vs. 6.3 %, P < 0.0001 and 26.4 vs. 11.6 % P < 0.0001, respectively) and independently (adjusted OR 5.15 [3.46-7.68], OR 6.63 [4.26-10.31], and OR 3.03 [2.04-4.50], respectively) associated with history of ischemic stroke. We also found that these three polymorphisms act synergistically in patients with stroke history. The TNFRSF11B gene polymorphisms studied are associated with history of ischemic stroke and synergistic effects between these genotypes might be potential markers for cerebrovascular disorders
Fibroblast growth factor 23 serum level in type 2 diabetic italian subjects with peripheral arterial disease and critical limb ischemia.
Full text linkOBJECTIVE: Fibroblast growth factor 23 (FGF23) was demonstrated to be involved in the occurrence and development of cardiovascular disease (CVD). The aim of this study was to investigate the potential role of FGF23 on presence and severity of peripheral arterial disease (PAD) in type 2 diabetic patients.
PATIENTS AND METHODS: In this study, we analyzed FGF23 serum levels in 413 type 2 diabetic patients with PAD and in 598 diabetic controls without lower limbs atherosclerosis.
RESULTS: We found that FGF23 median serum levels were significantly higher in patients than in diabetic controls (69.3 (58.8-75.1) pg/mL in PAD and 42.98 (37.1-49.8) pg/mL in subjects without PAD (p < 0.001) and were significantly and independently associated with critical limb ischemia (CLI) [OR, 7.69 (2.64-16.31); p = 0.001].
CONCLUSIONS: We have found, for the first time, that FGF23 could be associated with presence and severity of PAD in Italian patients with type 2 diabetes
Pro-Inflammatory Genetic Profiles in Subjects with Peripheral Arterial Occlusive Disease and Critical Limb Ischemia
No full textOBJECTIVES: Single nucleotide polymorphisms in genes encoding inflammatory molecules may determine genetic profiles associated with increased risk of development and progression of cardiovascular diseases. In this study, we evaluated distribution and reciprocal interaction of a set of functionally important polymorphisms of genes encoding prototypical inflammatory molecules in subjects with peripheral arterial occlusive disease (PAOD) and critical limb ischemia (CLI). We also investigated whether synergistic interactions between these pro-inflammatory gene polymorphisms influence the risk of PAOD and CLI. DESIGN, SUBJECTS, AND METHODS: A genetic association study including 157 PAOD patients and 206 controls. The following gene polymorphisms were analyzed: C-reactive protein (CRP) 1059 G/C, interleukin-6 (IL-6) -174 G/C, macrophage migration inhibitory factor (MIF) -173 G/C, monocyte chemoattractant protein (MCP-1) 2518 A/G, E-selectin (E-Sel) Ser128Arg, intercellular adhesion molecule-1 (ICAM-1) 469 E/K, matrix metalloproteinase (MMP)-1 -1607 1G/2G, MMP-3 -1171 5A/6A, and MMP-9-1563 C/T. RESULTS: We found that IL-6, E-sel, ICAM-1, MCP-1, MMP-1, and MMP-3 gene polymorphisms were significantly and independently associated with PAOD. We also found that these pro-inflammatory polymorphisms determine genetic profiles that are associated with different levels of risk for PAOD and CLI, depending on the number of high-risk genotypes concomitantly carried by a given individual. CONCLUSIONS: Proinflammatory genetic profiles are significantly more common in subjects with PAOD. Synergistic effects between pro-inflammatory genotypes might be potential markers for presence and severity of atherosclerotic disorder
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