Aim: Both vascular function and structure are independent predictors of cardiovascular events. The purpose of this study was to evaluate vascular function and structure of a leg artery in patients with peripheral artery disease (PAD).
Methods: We measured flow-mediated vasodilatation (FMD) and nitroglycerine-induced vasodilation (NID) as indices of vascular function and intima-media thickness (IMT) as an index of vascular structure of the popliteal artery in 100 subjects, including 20 patients with Buerger disease and 30 patients with atherosclerotic PAD, 20 age- and sex-matched subjects without Buerger disease (control group) and 30 age- and sex-matched patients without atherosclerotic PAD (control group).
Results: IMT was significantly larger in the Buerger group than in the control group (Buerger, 0.63± 0.20 mm; control, 0.50±0.07 mm; P=0.01), whereas there were no significant differences in FMD and NID between the two groups. IMT was significantly larger in the atherosclerotic PAD group than in the control group (atherosclerotic PAD, 0.80±0.22 mm; control, 0.65±0.14 mm; P＜0.01), and FMD and NID were significantly smaller in the atherosclerotic PAD group than in the control group (FMD: atherosclerotic PAD, 3.9%±1.1%; control, 5.0%±1.8%; P＜0.01; and NID: atherosclerotic PAD, 6.1%±2.0%; control, 8.4%±2.1%; P＜0.01).
Conclusion: These findings suggest that vascular function is preserved in patients with Buerger disease and that both vascular function and vascular structure are impaired in patients with atherosclerotic PAD.
Aim: The α1-antitrypsin–low-density lipoprotein complex (AT-LDL) and serum amyloid A-LDL complex (SAA-LDL) are oxidatively modified LDL complexes that promote atherosclerosis. The serum levels of AT-LDL and SAA-LDL are suggested to be increased by obesity and smoking. We have previously demonstrated that larger weight gain after smoking cessation (SC) perturbs a decrease in the serum level of AT-LDL at 3 months after SC. However, changes of these atherosclerotic makers ＞3 months after SC are unknown. This study investigated post-SC time-dependent changes in two atherogenic lipoproteins, AT-LDL and SAA-LDL, and in the extent of abdominal obesity.
Methods: In 50 outpatients who had continued SC for 1 year, we measured serum AT-LDL and SAA-LDL levels by the enzyme-linked immunosorbent assay before SC, and at 3 months and 1 year after SC.
Results: Both body mass index and waist circumstance significantly increased from pre-SC to 3 months after SC and from 3 months after SC to 1 year after SC. Although the serum levels of AT-LDL and SAA-LDL were unchanged from pre-SC to 3 months after SC, these levels decreased significantly from 3 months after SC to 1 year after SC.
Conclusions: The extent of abdominal obesity and levels of two atherogenic lipoproteins time-dependently change after SC. Although abdominal obesity progressively worsened after SC, the beneficial effect of non-smoking overcomes the potential vascular risks by cessation-associated obesity at 1 year after SC.
Aim: Sterol regulatory element-binding protein (SREBP)-1c is the dominant liver insulin-stimulated isoform and strongly correlates with diabetic dyslipidemia characterized by hyperinsulinemia [i.e., high-density lipoprotein cholesterol (HDL-C) levels and hypertriglyceridemia]. MicroRNA (miRNA) 33b is harbored in the intron of SREBP-1c and represses ATP-binding cassette, sub-family A, and member 1 (ABCA1) expression, essential for HDL formation. We measured plasma miRNA33b levels as possible biomarkers for diabetic dyslipidemia in patients with type 2 diabetes mellitus (T2DM) showing insulin resistance.
Methods: The participants included 50 patients with T2DM (M/F 31/19) enrolled in an educational program for controlling blood glucose levels at Hirosaki University Hospital. HbA1c, fasting plasma glucose, insulin, and lipid levels were determined. Plasma miRNA33b, miRNA33a and miRNA148a were quantified using a TaqMan® MicroRNA Assay, and values were corrected with reference to miRNA16.
Results: Mean BMI of participants were 28.2±6.6 (kg/m2) and the Homeostasis Model Assessment of Insulin Resistance was 4.3±2.7. Patients' laboratory findings indicated diabetic dyslipidemia with insulin resistance. Plasma miRNA33b/16 levels revealed a positive correlation with plasma insulin level (r=0.326, P=0.021), serum C-peptide (r=0.280, P=0.049), and triglyceride (r=0.351, P=0.012), but no association with HDL-C (r=-0.210, P=0.143). The blood level of miRNA33a was approximately 1/150th of that of miRNA33b and was not correlated with the above parameters.
Conclusion: We postulated that plasma miRNA33b may be useful as a new metabolic biomarker of dyslipidemia in patients with T2DM as well as metabolic syndrome via an insulin/SREBP-1c/miRNA33b/ABCA1 pathway.
Aim: To better understand the relationship between the interactions among rs17110453, rs751141, and rs9333025 variants and plasma levels of cytochrome P450 (CYP) metabolites, i.e.,20-hydroxyeicosatetraenoic acid (20-HETE), epoxyeicosatrienoic acids (EETs), and dihydroxyeicosatrienoic acids (DiHETEs) in ischemia stroke (IS).
Methods: We measured plasma CYP metabolite levels in 218 acute IS cases and 126 controls, and a subset of samples were assessed to further understand the association between relevant variants and IS risk in our previous study. We assessed the associations between variant interactions and levels of 20-HETE, EETs, and DiHETEs as well as the associations between levels of 20-HETE, EETs, and DiHETEs and IS risk after adjusting for other potential confounders. Furthermore, the association between variant interactions and IS risk after adjusting for other covariates, including CYP metabolites levels, was evaluated.
Results: The interactions among variants rs17110453, rs751141, and rs9333025 were significantly associated with high 20-HETE, high DiHETEs, and low EETs after adjusting for the status of diabetes mellitus and hypertension. High 20-HETE, high DiHETEs, and low EETs were independent risk factors for IS after adjusting for hypertension, diabetes mellitus, and the interactions among rs17110453, rs751141, and rs9333025. Furthermore, the interactions among rs17110453, rs751141, and rs9333025 were significantly associated with a higher risk of IS after adjusting for CYP metabolites (OR=2.02, 95% CI: 1.28–5.27, P=0.007).
Conclusion: The association between the interactions among rs17110453, rs751141, and rs9333025 and IS risk in Chinese population may be partly but not exclusively mediated by plasma levels of 20-HETE, EETs, and DHETs. Further well-designed studies are warranted to replicate this finding.
Aim: Endoplasmic reticulum stress (ERS) and inflammation participate in cardiac fibrosis. Importantly, a novel paracrine/autocrine peptide intermedin1-53 (IMD1-53) in the heart inhibits myocardial fibrosis in rats. However, the mechanisms are yet to be fully elucidated.
Methods: Myocardial fibrosis in apolipoprotein E-deficient (ApoE -/-) mice and neonatal rat cardiac fibroblasts (CFs) were induced using homocysteine (Hcy).
Results: IMD1-53 inhibited myocardial fibrosis in vivo and in vitro. Picrosirius red staining showed that IMD1-53 reduced myocardial interstitial collagen deposition in ApoE-/- mice treated with Hcy and decreased the expression of myocardial collagen I and III, which was further verified in rat CFs. IMD1-53 attenuated myocardial hypertrophy, as shown by cardiomyocyte cross-sectional area, ratio of heart weight to body weight, and mRNA levels of atrial natriuretic peptide and brain natriuretic peptide. IMD1-53 inhibited the upregulation of ERS hallmarkers such as glucose-regulated protein 78 (GRP78), GRP94, activating transcription factor 6 (ATF6), ATF4, inositol-requiring enzyme 1α, spliced-X-box-binding protein-1, protein kinase receptor-like ER kinase, and eukaryotic translation initiation factor 2α in mouse myocardium and rat CFs treated with Hcy. In addition, IMD1-53 decreased the production of inflammatory factors such as tumor necrosis factor-α, monocyte chemotactic protein-1, interleukin-6 (IL-6), and IL-1β in the mouse myocardium and rat CFs treated with Hcy. Concurrently, IMD1-53 ameliorated the expression of nuclear factor-κB, transforming growth factor-β1, and c-Jun N-terminal kinase in the mouse myocardium and rat CFs treated with Hcy.
Conclusions: IMD potentially protects against myocardial fibrosis induced by Hcy in ApoE-/- mice, possibly via attenuating myocardial ERS and inflammation.