Development of a novel fluorescent biosensor for dynamic monitoring of metabolic methionine redox status in cells and tissues

Aberrant production of reactive oxygen species (ROS) leads to tissue damage accumulation, which is associated with a myriad of human pathologies. Although several sensors have been developed for ROS quantification, their applications for ROS-related human physiologies and pathologies still remain problematic due to the unstable nature of ROS. Herein, we developed Trx1-cpYFP-fRMsr (TYfR), a genetically-encoded fluorescent biosensor with the remarkable specificity and sensitivity toward fMetRO (free Methionine-R-sulfoxide), allowing for dynamic quantification of physiological levels of fMetRO, a novel indicator of ROS and methionine redox status in vitro and in vivo. Moreover, using the sensor, we observed a significant fMetRO enrichment in serum from patients with acute coronary syndrome, one of the most severe cardiovascular diseases, which becomes more evident following percutaneous coronary intervention. Collectively, this study proposes that fMetRO is a novel biomarker of tissue damage accumulation in ROS-associated human pathologies, and that TYfR is a promising tool for quantifying fMetRO with potentials in versatile applications.ope

MicroRNA in the Diseased Pulmonary Vasculature: Implications for the Basic Scientist and Clinician

Since the first descriptions of their active functions more than ten years ago, small non-coding RNA species termed microRNA (miRNA) have emerged as essential regulators in a broad range of adaptive and maladaptive cellular processes. With an exceptionally rapid pace of discovery in this field, the dysregulation of many individual miRNAs has been implicated in the development and progression of various cardiovascular diseases. MiRNA are also expected to play crucial regulatory roles in the progression of pulmonary vascular diseases such as pulmonary hypertension (PH), yet direct insights in this field are only just emerging. This review will provide an overview of pulmonary hypertension and its molecular mechanisms, tailored for both basic scientists studying pulmonary vascular biology and physicians who manage PH in their clinical practice. We will describe the pathobiology of pulmonary hypertension and mechanisms of action of miRNA relevant to this disease. Moreover, we will summarize the potential roles of miRNA as biomarkers and therapeutic targets as well as future strategies for defining the cooperative actions of these powerful effectors in pulmonary vascular disease.ope

Successful endovascular treatment of iatrogenic coronary artery dissection extending into the entire ascending aorta

Iatrogenic acute dissection of the ascending aorta during percutaneous coronary intervention occurs rarely. Localized aortic dissections may be treated by sealing the entry with a coronary stent. However, extensive dissections may require a surgical intervention. A case of iatrogenic coronary dissection with extensive propagation into the ascending aorta during angioplasty of the right coronary artery is presented. The aortic dissection was successfully treated by stenting at the right coronary artery ostium. Follow-up computed tomography and coronary angiography showed complete resolution of aortic dissection.ope

Different association between renal dysfunction and clinical outcomes according to the presence of diabetes in patients undergoing endovascular treatment for peripheral artery disease

Objective: Although chronic kidney disease (CKD) and diabetes are important prognostic factors in patients with peripheral artery disease, there are limited data regarding the outcomes of endovascular treatment (EVT) according to the severity of CKD, especially in the presence of diabetes. This study sought to compare clinical outcomes of lower limb EVT between patients with and patients without CKD according to the presence of diabetes. Methods: Patients were enrolled from the Korean multicenter EVT registry and were divided according to the presence of diabetes, then further stratified by CKD (estimated glomerular filtration rate <60 mL/min/1.73 m(2)). The primary outcome was major adverse limb events (MALEs; a composite of reintervention for target limb, reintervention for target vessel, and unplanned major amputation) at 2 years. Results: A total of 3045 patients were eligible for analysis: 1277 nondiabetic patients (944 without CKD, 333 with CKD) and 1768 diabetic patients (951 without CKD, 817 with CKD). CKD was associated with a significantly increased risk of MALEs after EVT in diabetic patients (14.4% vs 9.9%; adjusted hazard ratio, 1.60; 95% confidence interval, 1.28-2.01; P < .001) but not in nondiabetic patients (7.6% vs 9.7%; adjusted hazard ratio, 0.78; 95% confidence interval, 0.53-1.14; P = .203; interaction P = .018). In analysis stratified by the severity of CKD among diabetic patients, end-stage renal disease was significantly associated with an increased risk of MALE. Conclusions: CKD was associated with a significantly higher risk of MALEs after EVT in diabetic patients but not in nondiabetic patients. The increased risk of MALEs was mainly driven by patients with end-stage renal disease.ope

Sex Differences in Outcomes Following Endovascular Treatment for Symptomatic Peripheral Artery Disease: An Analysis From the K- VIS ELLA Registry

Background With advances in peripheral artery disease ( PAD ) treatments such as endovascular treatment ( EVT ), personalized patient assessment is important. Data on sex differences in clinical outcome for PAD patients undergoing EVT have been limited, and studies have produced conflicting results. This study sought to compare midterm clinical outcomes between women and men in a large population of patients with PAD undergoing EVT . Methods and Results The K- VIS ELLA (Korean Vascular Intervention Society Endovascular Therapy in Lower Limb Artery Disease) registry is a nationwide, multicenter, observational study that includes 3073 PAD patients undergoing EVT . The study population was divided into men (n=2523) and women (n=550). The primary outcome was a composite of death, myocardial infarction, and major amputation; the secondary outcome included major adverse limb events. Women had more comorbidities and more severe and complex target lesions than men. Women showed higher rates of death, myocardial infarction, or major amputation than men (14.8% versus 9.8%, adjusted hazard ratio 1.350, 95% CI 1.017-1.792, P=0.038), and higher rates of major adverse limb events (19.9% versus 14.5%, adjusted hazard ratio 1.301, 95% CI 1.014-1.670, P=0.039) and procedural complications (10.2% versus 5.9%, P<0.001) based on multivariable analysis. In patients with claudication, the primary outcome incidence was significantly higher in women (hazard ratio 2.088, 95% CI 1.421-3.068, P<0.001). In contrast, there was no significant difference in primary outcome for patients with critical limb ischemia between the 2 groups (hazard ratio 1.164, 95% CI 0.800-1.694, P=0.426). A significant interaction ( P=0.035) between patient presentation and outcome was observed. Conclusions In a large population of patients with PAD undergoing EVT , women had higher rates of death, myocardial infarction, or major amputation than men and higher rates of complex lesions, procedural complications, and limb-specific adverse events.ope

Association between Body Mass Index and Clinical Outcomes of Peripheral Artery Disease after Endovascular Therapy: Data from K-VIS ELLA Registry

Background and objectives: Few studies have investigated the obesity paradox in clinical outcomes of peripheral artery disease (PAD). We investigated the association between body mass index (BMI) and clinical outcomes in PAD patients undergoing endovascular therapy (EVT). Methods: Patients (n=2,914) from the retrospective Korean Vascular Intervention Society Endovascular Therapy in Lower Limb Artery Disease registry were categorized according to BMI: underweight (<18.5 kg/m², n=204), normal weight (18.5-25 kg/m², n=1,818), overweight (25-30 kg/m², n=766), or obese (≥30 kg/m², n=126). Groups were compared for major adverse cardiovascular events (MACE) and major adverse limb events (MALE). Results: The underweight and obese groups were older and had more frequent critical limb ischemia and infrapopliteal artery disease than the normal or overweight groups (all p<0.001). Hypertension and diabetes were more frequent and current smoking was less frequent in the overweight and obese groups than the underweight or normal weight groups (all p <0.001). The underweight group showed the higher rates of MACE and MALE at 3 years (17.2%, 15.7%) compared with the normal weight (10.8%, 11.7%), overweight (8.4%, 10.7%), or obese groups (8.7%, 14.3%) (log-rank p<0.001, p=0.015). In contrast, the risk of MACE was lower in the overweight than the normal weight group (adjusted hazard ratio, 0.706; 95% CI, 0.537-0.928). Conclusions: In PAD patients undergoing EVT, underweight was an independent predictor for MACE and MALE, whereas MACE risk was lower for overweight than normal weight patients. Trial registration: ClinicalTrials.gov Identifier: NCT02748226.ope

Korean Multicenter Registry Study of EPIC Stents for the Treatment of Iliac Artery Disease: K-EPIC Registry

Background and objectives: The EPIC™ stent is a self-expanding, nitinol stent that has been designed to enhance flexibility and provide expansion within vessels. The aim of the present study was to investigate the clinical efficacy and safety of the EPIC™ stent when used to treat iliac artery diseases in a prospective Korean multicenter registry. Methods: A total of 138 patients with iliac artery diseases who received endovascular treatment with EPIC™ stents at 9 Korean sites were enrolled in a prospective cohort and followed for 1 year. The primary endpoint was the 1-year freedom from target lesion revascularization (TLR). The secondary endpoints were 1-year clinical patency and freedom from major adverse events (MAEs). Results: The mean age of the study subjects was 66.8±8.5 years and most subjects were male (86.2%). The most frequent lesion type was Trans-Atlantic Inter-Society Consensus B (43.5%) and the majority (56.5%) of the target lesions were located in the common iliac artery. Procedural success was obtained in 99.3% of patients. The freedom from TLR and the clinical patency at 1-year follow-up were 94.9% and 92.3%, respectively. The 1-year rate of MAEs was 5.1%. Combined coronary artery disease (hazard ratio [HR], 5.91; 95% confidence interval [CI], 1.13-30.89; p=0.035) and smaller stent diameter (HR, 0.38; 95% CI, 0.17-0.88; p=0.023) were identified as independent risk factors of TLR after EPIC™ stent implantation. Conclusions: The EPIC™ stents demonstrated excellent immediate and 1-year efficacy and safety outcomes in iliac artery lesions in this multicenter, prospective, registry-based study.ope

Differential efficacy between stenting and plain balloon angioplasty for femoropopliteal disease with or without total occlusion

Background/aims: Whether the presence of chronic total occlusion (CTO) affects patency after stenting in femoropopliteal lesions is unknown. We determined the effects of plain balloon angioplasty (POBA) in comparison with those of stenting on patency for femoropopliteal CTO and stenosis (non-CTO). Methods: We analyzed data from the Korean Vascular Intervention Society Endovascular Therapy in Lower-Limb Artery Diseases Registry, a multicenter cohort of patients with lower extremity peripheral arterial disease. Data from 1,329 patients and 1558 limbs treated with endovascular intervention for at least one femoropopliteal lesion were evaluated. Results: Among the 1,558 limbs, 345, 432, 275, and 506 were in the non-CTO-POBA, non-CTO-stent, CTO-POBA, and CTO-stent groups, respectively. During follow-up, loss of clinical primary patency, a composite of freedom from restenosis or clinically driven target lesion revascularization, occurred in 65 (18.8%), 68 (15.7%), 62 (22.5%), and 113 limbs (22.3%) in the non-CTO-POBA, non-CTO-stent, CTO-POBA, and CTO-stent groups, respectively. The patients in the non-CTO-stent group showed a significantly better clinical primary patency than those in the no-CTO-POBA group, whereas those in the CTO-stent and CTO-POBA groups showed no significant differences. After inverse probability of treatment weighting to balance the differences among covariates between the non-CTO-stent and non-CTO-POBA groups, the non-CTO-stent group still showed superior clinical primary patency as compared with the non-CTO-POBA group. Conclusion: In the patients with femoropopliteal stenosis without CTO, stenting resulted in better clinical outcomes than balloon angioplasty. The presence of CTO in the femoropopliteal lesion should be considered when selecting a suitable device for performing endovascular procedures.ope

Influence of preprocedural glycemic control on clinical outcomes of endovascular therapy in diabetic patients with lower extremity artery disease: an analysis from a Korean multicenter retrospective registry cohort

Background: The influence of intensive glucose control in diabetic patients on the macrovascular outcomes is controversial. Thus, this study aimed to elucidate the effect of preprocedural hemoglobin A1c (HbA1c) on clinical outcomes after endovascular therapy for lower extremity artery disease (LEAD) in diabetic patients. Methods: Diabetic patients were enrolled from the retrospective cohorts of a Korean multicenter endovascular therapy registry and were divided according to the HbA1c level during index admission into the optimal (< 7.0%) or suboptimal (≥ 7.0%) glycemic control groups. The primary endpoints were major adverse limb events (MALE, a composite of major amputation, minor amputation, and reintervention). Results: Of the 1103 patients enrolled (897 men, mean age 68.2 ± 8.9 years), 432 (39.2%) were classified into the optimal glycemic control group and 671 (60.8%) into the suboptimal glycemic control group. In-hospital events and immediate procedural complications were not different between the two groups. The suboptimal group showed a trend towards a higher incidence of MALE than the optimal group (log-rank p = 0.072). Although no significant differences were found between the two groups in terms of overall survival or amputation, the risk of reintervention was significantly higher in the suboptimal group (log-rank p = 0.048). In the multivariate Cox regression model, suboptimal glycemic control was one of the independent predictors for reintervention. When our data were analyzed according to the initial presentation, suboptimal preprocedural HbA1c significantly increased the incidence of MALE compared with optimal preprocedural HbA1c only in patients with intermittent claudication. Conclusion: In diabetic patients undergoing endovascular therapy for LEAD, suboptimal preprocedural HbA1c is associated with an increased risk of adverse limb events, especially in patients with intermittent claudication. Further prospective research will be required to validate the role of more intensive glycemic control on the reduction of adverse limb events in diabetic patients undergoing endovascular therapy for LEAD.ope

Long-term Clinical Outcomes and Prognostic Factors After Endovascular Treatment in Patients With Chronic Limb Threatening Ischemia

Background and objectives: Endovascular therapy (EVT) first strategy has been widely adopted for the treatment of chronic limb threatening ischemia (CLTI) patients in real-world practice. This study aimed to investigate long-term outcomes of CLTI patients who underwent EVT and identify prognostic factors. Methods: From the retrospective cohorts of a Korean multicenter endovascular therapy registry, 1,036 patients with CLTI (792 men, 68.8 ± 9.5 years) were included. The primary endpoint was amputation-free survival (AFS) defined as the absence of major amputation or death. Secondary endpoints were major adverse limb events (MALE; a composite of major amputation, minor amputation, and reintervention). Results: Five-year AFS and freedom from MALE were 69.8% and 61%, respectively. After multivariate analysis, age (hazard ratio [HR], 1.476; p<0.001), end-stage renal disease (ESRD; HR, 2.340; p<0.001), Rutherford category (RC) 6 (HR, 1.456; p=0.036), and suboptimal EVT (HR, 1.798; p=0.005) were identified as predictors of major amputation or death, whereas smoking (HR, 0.594; p=0.007) was protective. Low body mass index (HR, 1.505; p=0.046), ESRD (HR, 1.648; p=0.001), femoropopliteal lesion (HR, 1.877; p=0.004), RC-6 (HR, 1.471; p=0.008), and suboptimal EVT (HR, 1.847; p=0.001) were predictors of MALE. The highest hazard rates were observed during the first 6 months for both major amputation or death and MALE. After that, the hazard rate decreased and rose again after 3-4 years. Conclusions: In CLTI patients, long-term outcomes of EVT were acceptable. ESRD, RC-6, and suboptimal EVT were common predictors for poor clinical outcomes. Trial registration: ClinicalTrials.gov Identifier: NCT02748226.ope