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In a randomized trial, 154 patients with femoropopliteal-artery disease who were undergoing angioplasty were assigned to treatment with a paclitaxel-coated angioplasty balloon, an uncoated balloon with paclitaxel dissolved in the contrast medium, or an uncoated balloon without paclitaxel (control treatment). Late lumen loss, restenosis at 6 months, and target-lesion revascularization at 6, 12, and 24 months were significantly reduced with the paclitaxel-coated balloon but not with paclitaxel-containing contrast medium. In patients with femoropopliteal-artery disease who were undergoing angioplasty, late lumen loss, restenosis at 6 months, and target-lesion revascularization at 6, 12, and 24 months were significantly reduced with a paclitaxel-coated balloon but not with paclitaxel-containing contrast medium. Percutaneous transluminal angioplasty for revascularization of the superficial femoral artery has an initial technical success rate of more than 95%. 1 However, restenosis occurs in 40 to 60% of the treated segments after 6 to 12 months 2 – 4 ; these rates are much higher than restenosis rates in other vascular beds, such as the coronary and renal arteries. 5 Stenting is more effective than balloon angioplasty for preventing restenosis in the coronary circulation, but a benefit of stenting in the vessels of the lower extremities remains to be confirmed. 6 – 9 Several other attempts to increase long-term patency in peripheral vascular disease have . . .

In a 2-year clinical trial, the addition of ezetimibe to simvastatin had no effect on the progression of atherosclerosis, as measured by carotid-artery intima–media thickness, despite the additional lowering of levels of low-density lipoprotein cholesterol and C-reactive protein by ezetimibe when added to simvastatin. However, the study was not powered to assess clinical end points. The addition of ezetimibe to simvastatin had no effect on the progression of atherosclerosis, as measured by carotid-artery intima–media thickness, despite the additional lowering of levels of low-density lipoprotein cholesterol and C-reactive protein. A reduction in levels of low-density lipoprotein (LDL) cholesterol constitutes one of the cornerstones in the prevention of cardiovascular disease. In recent trials comparing various statins or the same statin at various doses, aggressive therapy to lower LDL cholesterol levels was associated with a reduction in rates of cardiovascular events. 1 – 4 However, administration of the highest approved statin dose offers only limited additional lowering of LDL cholesterol at the expense of an increased incidence of side effects. 5 Therefore, novel compounds that further reduce LDL cholesterol levels when added to statin therapy are of interest. A recently introduced compound, ezetimibe, selectively . . .

In-stent restenosis (ISR) represents a major drawback of stented superficial femoral arteries (SFAs). Motivated by the high incidence and limited knowledge of ISR onset and development in human SFAs, this study aims to (i) analyze the lumen remodeling trajectory over 1-year follow-up period in human stented SFAs and (ii) investigate the impact of altered hemodynamics on ISR initiation and progression. Ten SFA lesions were reconstructed at four follow-ups from computed tomography to quantify the lumen area change occurring within 1-year post-intervention. Patient-specific computational fluid dynamics simulations were performed at each follow-up to relate wall shear stress (WSS) based descriptors with lumen remodeling. The largest lumen remodeling was found in the first post-operative month, with slight regional-specific differences (larger inward remodeling in the fringe segments, p < 0.05). Focal re-narrowing frequently occurred after 6 months. Slight differences in the lumen area change emerged between long and short stents, and between segments upstream and downstream from stent overlapping portions, at specific time intervals. Abnormal patterns of multidirectional WSS were associated with lumen remodeling within 1-year post-intervention. This longitudinal study gave important insights into the dynamics of ISR and the impact of hemodynamics on ISR progression in human SFAs.

Carotid and femoral plaques exhibit varying degrees of stability; however, the relationships of different genes/cell types with plaque embolism are poorly understood. We evaluated differential gene/cell expression and investigated the cells/genes associated with carotid and femoral artery plaque embolism. sc-RNA-seq and bulk RNA data were obtained to identify differentially expressed genes (DEGs). Seven machine learning models were trained, and the top 10 DEGs across all models were selected. The most disturbed cells in carotid and femoral artery plaques were identified using Augur, while the genes and cells in the carotid plaque associated with embolism were analyzed through scPagwas. The differences in most disturbed cells and embolism-related cells were further analyzed. Compared with femoral plaques, carotid plaques had 80 downregulated and 90 upregulated genes. Machine learning identified the key DEGs between carotid and femoral plaques were predominantly from the HOX gene family. Natural Killer (NK) cells were the most significantly disturbed cells between carotid and femoral plaques, and they may be most strongly associated with plaque embolism. Among the differential genes in NK cells, CD2 was most associated with embolism. Our research may offer new insights into atherosclerosis at different locations.

Blood vessel growth in adult organisms involves the following two fundamental processes: angiogenesis, the proliferation and extension of capillary networks; and arteriogenesis, the growth of functional arteries. We provide a protocol for the evaluation of postnatal arteriogenesis and angiogenesis in a mouse model of hind-limb ischemia. Surgical ligation of the femoral artery at a specific site triggers arteriogenesis of small, pre-existing collateral arteries into functional conduit vessels proximally and ischemic angiogenesis distally. The vascular response to hind-limb ischemia can be readily evaluated by laser Doppler-based perfusion measurements, histological quantification of arteriogenesis and angiogenesis or whole-mount visualization of arteries in limb muscles. Depending on the experimental design, the protocol takes between 4 and 29 d to complete; however, the net working time is about 2 d per mouse. The concurrent and specific analysis of postnatal angiogenesis and arteriogenesis in the same animal is a unique feature of the protocol.

We have shown that both insulin and resveratrol (RSV) decrease neointimal hyperplasia in chow-fed rodents via mechanisms that are in part overlapping and involve the activation of endothelial nitric oxide synthase (eNOS). However, this vasculoprotective effect of insulin is abolished in high-fat-fed insulin-resistant rats. Since RSV, in addition to increasing insulin sensitivity, can activate eNOS via pathways that are independent of insulin signaling, such as the activation of sirtuin 1 (SIRT1) and AMP-activated kinase (AMPK), we speculated that unlike insulin, the vasculoprotective effect of RSV would be retained in high-fat-fed rats. We found that high-fat feeding decreased insulin sensitivity and increased neointimal area and that RSV improved insulin sensitivity (p < 0.05) and decreased neointimal area in high-fat-fed rats (p < 0.05). We investigated the role of SIRT1 in the effect of RSV using two genetic mouse models. We found that RSV decreased neointimal area in high-fat-fed wild-type mice (p < 0.05), an effect that was retained in mice with catalytically inactive SIRT1 (p < 0.05) and in heterozygous SIRT1-null mice. In contrast, the effect of RSV was abolished in AMKPα2-null mice. Thus, RSV decreased neointimal hyperplasia after arterial injury in both high-fat-fed rats and mice, an effect likely not mediated by SIRT1 but by AMPKα2.

Vascular calcification (V) is an independent risk factor for all-cause and cardiovascular mortality. Vascular smooth muscle cells (VSMCs) play a major role in VC as they can acquire mineralizing properties when exposed to osteogenic conditions. Despite its clinical impact, there are still no dedicated therapeutic strategies targeting VC. To address this issue, we used human calcified and non-calcified atherosclerotic arteries (ECLAGEN Biocollection) to screen and identify microRNA (miR) associated with VC. We combined non-biased miRNomic (microfluidic arrays) and transcriptomic analysis to select miR candidates and their putative target genes with expression associated with VC and ossification. We further validated miR functional regulation and function in relation to cell mineralization using primary human VSMCs. Our study identified 12 miRs associated with VC in carotid and femoral arteries. Among those, we showed that miR136, miR155, and miR183 expression were regulated during VSMC mineralization and that overexpression of these miRs promoted VSMC mineralization. Cross-analysis of this miRNomic and a transcriptomic analysis led to the identification of CD73 and Smad3 pathways as putative target genes responsible for mediating the miR155 pro-mineralizing function. These results highlight the potential benefit of miR155 inhibition in limiting VC development in peripheral atherosclerotic arteries.

This study aimed to explore thrombolysis therapy based on ultrasound combined with urokinase and Arg–Gly–Asp sequence (RGDS)-targeted microbubbles by evaluating the histological changes in a thrombotic rabbit model. Forty-two New Zealand rabbits featuring platelet-rich thrombi in the femoral artery were randomized to (n = 6/group): ultrasound alone (US); urokinase alone (UK); ultrasound plus non-targeted microbubbles (US + M); ultrasound plus RGDS-targeted microbubbles (US + R); RGDS-targeted microbubbles plus urokinase (R + UK); ultrasound, non-targeted microbubbles and urokinase (US + M + UK); and ultrasound, RGDS-targeted microbubbles and urokinase (US + R + UK) groups. Diagnostic ultrasound was used transcutaneously over the thrombus for 30 min. We evaluated the thrombolytic effect based on ultrasound thrombi detection, blood flow, and histological observations. Among all study groups, complete recanalization was achieved in the US + R + UK group. Hematoxylin and eosin staining showed that the thrombi were completely dissolved. Scanning electron microscopy examination demonstrated that the fiber network structure of the thrombi was damaged. Transmission electron microscopy showed that the thrombus was decomposed into high electron-dense particles. Histology for von Willebrand factor and tissue factor were both negative in the US + R + UK group. This study revealed that a thrombolytic therapy consisting of diagnostic ultrasound together with RGDS-targeted and urokinase coupled microbubbles.

Genetic P300/CBP-associated factor (PCAF) variation affects restenosis-risk in patients. PCAF has lysine acetyltransferase activity and promotes nuclear factor kappa-beta (NFκB)-mediated inflammation, which drives post-interventional intimal hyperplasia development. We studied the contributing role of PCAF in post-interventional intimal hyperplasia. PCAF contribution to inflammation and intimal hyperplasia was assessed in leukocytes, macrophages and vascular smooth muscle cells (vSMCs) in vitro and in a mouse model for intimal hyperplasia, in which a cuff is placed around the femoral artery. PCAF deficiency downregulate CCL2, IL-6 and TNF-alpha expression, as demonstrated on cultured vSMCs, leukocytes and macrophages. PCAF KO mice showed a 71.8% reduction of vSMC-rich intimal hyperplasia, a 73.4% reduction of intima/media ratio and a 63.7% reduction of luminal stenosis after femoral artery cuff placement compared to wild type (WT) mice. The association of PCAF and vascular inflammation was further investigated using the potent natural PCAF inhibitor garcinol. Garcinol treatment reduced CCL2 and TNF-alpha expression, as demonstrated on cultured vSMCs and leukocytes. To assess the effect of garcinol treatment on vascular inflammation we used hypercholesterolemic ApoE*3-Leiden mice. After cuff placement, garcinol treatment resulted in reduced arterial leukocyte and macrophage adherence and infiltration after three days compared to untreated animals. These results identify a vital role for the lysine acetyltransferase PCAF in the regulation of local inflammation after arterial injury and likely the subsequent vSMC proliferation, responsible for intimal hyperplasia.

While the efficacy and safety of drug-coated balloons (DCBs) for treating short femoropopliteal lesions are well-established, evidence on long-term outcomes for long lesions remains limited. This study aims to compare the 2-year clinical outcomes of DCB angioplasty between long and short femoropopliteal lesions and identify risk factors for patency loss. This real-world and single-center cohort study included 234 patients with de novo stenosis or restenosis or occlusion of the femoropopliteal arteries (115 long lesions > 15 cm, 141 short lesions ≤ 15 cm) who underwent successful DCB treatment from January 2019 to December 2021 at Peking Union Medical College Hospital. The primary safety endpoint was defined as freedom from major adverse events (death, target limb amputation or thrombosis). The primary effectiveness endpoint was defined as 2-year primary patency, defined as freedom from both clinically driven target lesion revascularization (CD-TLR) and restenosis. Primary patency was significantly lower in long lesions (48.3% vs. 62.5%, p = 0.005), while freedom from CD-TLR rate showed no difference (83.6% vs. 87.4%, p = 0.25). Long lesions exhibited higher rates of occlusions (p < 0.001), in-stent restenosis (p = 0.025), and advanced ischemia (Rutherford Clinical Category (RCC) 4–6, p = 0.038). Multivariate analysis identified lesion length > 15 cm (p = 0.017) and RCC 4–6 (p = 0.026) as independent predictors of patency loss. Within the long lesion subgroup, only RCC 4–6 maintained prognostic significance (p = 0.027), and no significant predictors emerged in the short lesion group. Major adverse events occurred in 12.4% of patients, predominantly in long lesions with severe comorbidities. While DCB angioplasty achieved acceptable 2-year safety outcomes, long femoropopliteal lesions (> 15 cm) demonstrated significantly inferior primary patency compared to short lesions (48.3% vs. 62.5%, p = 0.005). Advanced ischemia (RCC 4–6) is a risk factor for patency loss.