Obesity is known to increase breast cancer risk and aggressiveness in postmenopausal luminal breast cancer and obesity-driven dysfunctional metabolic activity in visceral adipose tissue (VAT) is considered as one of the principal underlying mechanism. We aimed to investigate the relationship between VAT metabolic activity evaluated by preoperative 18F-FDG PET/CT and axillary lymph node (ALN) metastasis in postmenopausal luminal breast cancer patients. In total, 173 patients were enrolled in study. They all underwent preoperative 18F-FDG PET/CT and surgery. VAT metabolic activity was defined as the maximum standardized uptake value (SUVmax) of VAT divided by the SUVmax of subcutaneous adipose tissue (V/S ratio). In luminal breast cancer, the patients with ALN metastasis showed significantly higher V/S ratio than the patients without ALN metastasis. Furthermore, V/S ratio was significantly associated with ALN metastasis in luminal breast cancer patients. Erythrocyte sedimentation rate, which reflect the systemic inflammation, was significantly higher in ALN metastasis group than the negative ALN metastasis group in luminal breast cancer patients and showed significant positive correlation with V/S ratio. V/S ratio significantly affects the ALN metastasis status in postmenopausal luminal breast cancer patients and it may be useful as a potential biomarker of obesity-driven systemic inflammation associated with tumor aggressiveness.

Synthetic vascular smooth muscle cells (VSMCs) play important roles in atherosclerosis, in-stent restenosis, and transplant vasculopathy. We investigated the synthetic activity of VSMCs in the atherosclerotic carotid artery using 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET). Atherosclerosis was induced in rats by partial ligation of the right carotid artery coupled with an atherogenic diet and vitamin D injections (2 consecutive days, 600,000 IU/day). One month later, rats were imaged by F-18 FDG PET. The atherosclerotic right carotid arteries showed prominent luminal narrowing with neointimal hyperplasia. The regions with neointimal hyperplasia were composed of α-smooth muscle actin-positive cells with decreased expression of smooth muscle myosin heavy chain. Surrogate markers of synthetic VSMCs such as collagen type III, cyclophilin A, and matrix metallopeptidase-9 were increased in neointima region. However, neither macrophages nor neutrophils were observed in regions with neointimal hyperplasia. F-18 FDG PET imaging and autoradiography showed elevated FDG uptake into the atherosclerotic carotid artery. The inner vessel layer showed higher tracer uptake than the outer layer. Consistently, the expression of glucose transporter 1 was highly increased in neointima. The present results indicate that F-18 FDG PET may be a useful tool for evaluating synthetic activities of VSMCs in vascular remodeling disorders.

Background Inflamed visceral adipose tissue (VAT) facilitates chronic inflammation in atherosclerotic lesions thereby leading to increased risk of coronary artery disease (CAD). In this study, we evaluated the glucose uptake of VAT and the carotid artery with 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET/CT) and their association with CAD, including acute myocardial infarction (AMI). Methods A total of 90 participants were enrolled (32 with AMI, 33 with chronic stable angina; CSA, and 25 control participants) and undertook 18F-FDG PET/CT. VAT glucose uptake was measured by using maximum standardized uptake value (SUVmax) of VAT region. The target-to-background ratio (TBR) of carotid artery was defined as the SUVmax of carotid artery divided by the SUVmax of jugular vein. The SUVmax of spleen, bone-marrow (BM), and high-sensitivity C-reactive protein (hsCRP) were used for the assessment of systemic inflammatory activity. Results VAT SUVmax was highest in participants with AMI, intermediate in participants with CSA, and lowest in control participants. Carotid artery TBR and systemic inflammatory surrogate markers including spleen SUVmax, BM SUVmax, and hsCRP were also higher in the AMI group than in the CSA or control group. Furthermore, VAT SUVmax showed significant positive correlation with carotid artery TBR, spleen SUVmax, BM SUVmax, and hsCRP. In multivariate linear regression and logistic regression analyses, VAT SUVmax was independently associated with carotid artery TBR and AMI. Conclusions Glucose uptake of VAT assessed by 18F-FDG PET/CT was associated with the severity of CAD and synchronized with the carotid artery inflammation in participants with CAD.

ObjectivesObesity plays pivotal roles in the increased risk of cardiometabolic disease via induction of the inflammatory reaction from macrophages in visceral adipose tissue (VAT), which may elevate the inflammatory activity of VAT. This prospective study aimed to evaluate whether the inflammatory activity of VAT existed in association with systemic inflammation, and whether exercise could ameliorate the inflammatory activity of VAT assessed by 18F‐fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in obese women.Design and PatientsA total of 23 obese women who participated in an exercise program were included. Subjects underwent 18F‐FDG PET/CT before the start of the exercise program (baseline) and after the completion of the 3‐month exercise program. For the assessment of VAT metabolic activity, the maximum standardized uptake value (SUVmax) and the mean standardized uptake value (SUVmean) were measured. The SUVmax of spleen, bone marrow (BM) and the high‐sensitivity C‐reactive protein (hsCRP) were used as a surrogate marker for systemic inflammation.ResultsBaseline SUVmax of VAT was positively correlated with the SUVmax of spleen, BM and hsCRP, whereas VAT SUVmean was not correlated. Exercise reduced SUVmax of VAT in addition to adiposity, the SUVmax of spleen, BM and hsCRP. However, VAT SUVmean was not significantly changed. Furthermore, the association of SUVmax of VAT, and the SUVmax of spleen, BM and hsCRP was no longer relevant after exercise.ConclusionIn obese women, the SUVmax of VAT assessed by 18F‐FDG PET/CT was associated with systemic inflammation and exercise reduced the SUVmax of VAT and abrogated its association with systemic inflammation.

Background Neointimal hyperplasia and its related arterial stiffness are the crucial pathophysiological features in atherosclerosis and in-stent restenosis. Cluster of differentiation 147 (CD147), a member of the immunoglobulin super family that induces the expression of matrix metalloproteinase-9 (MMP-9) by dimerization, may play important roles in neointimal hyperplasia and may therefore be an effective target for the treatment of this condition. Here, we investigated whether a novel CD147 inhibitor SP-8356 ((1S,5R)-4-(3,4-dihydroxy-5-methoxystyryl)-6,6-dimethylbicyclo[3.1.1]hept-3-en-2-one) reduces neointimal hyperplasia and arterial stiffness in a rat model of partial carotid artery ligation. Methods Neointimal hyperplasia was induced in Sprague–Dawley rats by partial ligation of the right carotid artery combined with a high fat diet and vitamin D injection. Rats were subdivided into vehicle, SP-8356 (50 mg/kg), and rosuvastatin (10 mg/kg) groups. The drugs were administrated via intraperitoneal injections for 4 weeks. The elasticity of blood vessels was assessed by measuring pulse wave velocity using Doppler ultrasonography before sacrifice. Histomolecular analysis was carried out on harvested carotid arteries. Results SP-8356 significantly reduced MMP activity by inhibiting CD147 dimerization. SP-8356 reduced neointimal hyperplasia and prevented the deterioration of vascular elasticity. SP-8356 had a greater inhibitory effect on neointimal hyperplasia than did rosuvastatin. Furthermore, rosuvastatin did not improve vascular elasticity. SP-8356 increased the expression of smooth muscle myosin heavy chain (SM-MHC), but decreased the expression of collagen type III and MMP-9 in the neointimal region. In contrast to SP-8356, rosuvastatin did not alter the expression of SM-MHC or MMP-9. Conclusions The ability of SP-8356 to reduce neointimal hyperplasia and improve arterial stiffness in affected carotid artery suggests that SP-8356 could be a promising therapeutic drug for vascular remodeling disorders involving neointimal hyperplasia and arterial stiffness.