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To evaluate the association of perioperative inflammatory status, as determined using the neutrophil-to-lymphocyte ratio (NLR) and high-sensitivity C-reactive protein (hs-CRP) level, with the efficacy of femoropopliteal paclitaxel-coated balloon (PCB) angioplasty.The data of 122 patients (138 limbs) were retrospectively analyzed (median follow-up time, 21 months). The pre- and postoperative NLRs and hs-CRP levels were evaluated to determine their predictive value for mid-term primary patency and clinically driven target lesion revascularization (CD-TLR) during follow-up. Cox regression and Kaplan-Meier survival analyses were performed to investigate the predictive value of the inflammatory parameters and clinical risk factors.The study population had a median age of 67.2 ± 9.2 years, and 85.2 ± 3% of them were men. Approximately, 18.0 ± 3% of the cases were classified under Rutherford grade II; 52.5 ± 4%, grade III; 24.6 ± 3%, grade IV; 4.1 ± 1%, grade V; and 0.8 ± 0.7%, grade VI. The 12- and 24-month cumulative patency rates were 81.2 ± 27.0% and 60.4 ± 30.1%, respectively, and the freedom from CD-TLR rates were 90.8 ± 19.1% and 82.5 ± 28.3%, respectively. Severe lesion calcification was identified as an independent risk factor for CD-TLR (hazard ratio [HR] = 1.51, 95% confidence interval [CI] = 1.05-3.01), while hypertension was found as a protective factor for primary patency (HR = 0.54, 95% CI = 0.30-0.93). The patients with Trans-Atlantic Inter-Society Consensus (TASC) C/D lesions had more than a 2-fold increased adjusted risk of both primary patency loss and CD-TLR compared with those with TASC A/B lesions (HR = 2.44 for primary patency loss; HR = 2.51 for CD-TLR). The perioperative NLRs and hs-CRP levels were stratified into three grades. The patients with a higher preoperative hs-CRP level (9.2 vs. 0.6-9.2 vs.0.6 mg/L by each tertile) had a 2.4-fold increased adjusted risk of primary patency loss compared with those with a lower preoperative hs-CRP level. The patients with a higher hs-CRP level on the first postoperative day (13.0 vs. 7.7-13.0 vs.7.7 mg/L by each tertile) had a 1.8-fold increased adjusted risk of primary patency loss compared with those with a lower hs-CRP level. In contrast, the patients with a higher NLR at 4-6 hr postoperatively (3.6 vs. 2.5-3.6 vs.2.5 by each tertile) showed better primary patency (adjusted HR = 0.57) than did those with a lower NLR. A higher hs-CRP level on the first postoperative day was the only inflammatory marker associated with a high risk of CD-TLR (adjusted HR = 2.37).Perioperative inflammatory status serves as a valuable prognostic parameter for assessing the potential risk stratification of outcomes after paclitaxel-coated balloon (PCB) angioplasty.

Epidemiology survey indicated that cigarette smoking is a risk factor of diabetes. However, the precise mechanisms remain to be clarified. In this study, we found that smoking caused metabolic malfunctions on pancreas and liver in experimental animal model. These were indicated by hyperglycemia, increased serum hemoglobin A1c level and decreased insulin secretion, inhibition of liver glycogen synthase (LGS), and hepatic glycogen synthesis. Mechanistic studies revealed that all these alterations were caused by the inflammatory reaction and reactive oxygen species (ROS) induced by the smoking. Melatonin treatment significantly preserved the functions of both pancreas and liver by reducing β cell apoptosis, CD68‐cell infiltration, ROS production, and caspase‐3 expression. The siRNA‐knockdown model identified that the protective effects of melatonin were mediated by melatonin receptor‐2 (MT2). This study uncovered potentially underlying mechanisms related to the association between smoking and diabetes. In addition, it is, for first time, to report that melatonin effectively protects against smoking‐induced glucose metabolic alterations and the signal transduction pathway of melatonin is mainly mediated by its MT2 receptor. These observations provide solid evidence for the clinically use of melatonin to reduce smoking‐related diabetes, and the therapeutic regimens are absent currently.

Osteopontin (OPN) is involved in mineral metabolism and the inflammatory response while diabetes mellitus is associated with severe and extensive vascular calcification. Therefore, we speculated that OPN could be a key factor in the calcification and dysfunction of blood vessels exposed to high glucose. To identify the relationship between high glucose and OPN, we used high glucose medium to stimulate smooth muscle cells (SMCs) and vascular endothelial cells (VECs) in vitro and diabetic rats for in vivo analyses. As assessed by flow cytometry and western blots, SMC and VEC apoptosis levels increased with high glucose. Potassium and calcium uptake by cells were also increased with high glucose. These findings demonstrated the relationship between mineral metabolism and high glucose. Western blot and quantitative real time polymerase chain reaction analyses demonstrated that OPN increased in vitro with high glucose stimulation. The inflammatory factor ICAM1 and the inhibitory phosphorylation of endothelial nitric-oxide synthase (eNOS) (Thr495) were also upregulated by high glucose. In contrast, the anti-inflammatory factor Nrf2 and the activating phosphorylation of eNOS (Ser1177) were downregulated. Similar to the change of OPN, phosphorylated P38 was increased with high glucose. SB203580, an inhibitor of P38 phosphorylation, downregulated the expression of OPN and related inflammatory factors. Additionally, OPN was increased in the aortas and plasma of diabetic rats. In conclusion, our findings demonstrate that high glucose can induce the expression of OPN, which may be a key factor in the calcification and dysfunction of the vascular wall in diabetes.

Adipose tissue can modulate disease processes in a depot-specific manner. However, the functional properties of perivascular adipocytes, and their influence on the pathophysiology of blood vessel walls, remain to be determined. In this study, we aimed to investigate whether perivascular adipose tissue could have an ameliorative effect on blood vessels damaged in diabetes. Using in vitro coculture, and in vivo transplantation model simulating diabetic angioplasty-induced injury, we showed that perivascular adipose tissue has an important function in protecting blood vessels from high glucose impairment. Levels of inflammatory cytokines, including intercellular cell adhesion molecule-1 and osteopontin, were markedly reduced, whereas that of endothelial nitric-oxide synthase was markedly elevated in vascular walls. These depot-specific differences in blood vessels exposed to high levels of glucose were demonstrable both in vivo, with transplanted adipose tissues, and in vitro, when vascular endothelial cells were cocultured with adipocytes. In addition, intimal hyperplasia was also decreased by transplanted perivascular adipose tissue after balloon injury combined with hyperglycemia. We conclude that perivascular adipocytes can reduce inflammation in blood vessels and promote the normal function of endothelium, which could afford a new therapeutic strategy in vascular walls damaged by diabetes.

Cigarette smoke is not only a profound independent risk factor of atherosclerosis, but also aggravates restenosis after vascular angioplasty. Heme oxygenase-1 (HO-1) is an endogenous antioxidant and cytoprotective enzyme. In this study, we investigated whether HO-1 upregulating by hemin, a potent HO-1 inducer, can protect against cigarette smoke-induced restenosis in rat's carotid arteries after balloon injury. Results showed that cigarette smoke exposure aggravated stenosis of the lumen, promoted infiltration of inflammatory cells, and induced expression of inflammatory cytokines and adhesion molecules after balloon-induced carotid artery injury. HO-1 upregulating by hemin treatment reduced these effects of cigarette smoke, whereas the beneficial effects were abolished in the presence of Zincprotoporphyrin IX, an HO-1 inhibitor. To conclude, hemin has potential therapeutic applications in the restenosis prevention after the smokers' vascular angioplasty.