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A man in his 70s visited the hospital for chronic kidney disease with hypertension. He had anuria for several days before visiting the hospital. His creatinine level rose to 8.97 mg/dL (from 3 mg/dL) and his systemic blood pressure increased to 183 mm Hg. Other uraemic symptoms were also observed, and he was therefore admitted to the hospital and started continuous haemodiafiltration. MRI and angiography showed a highly stenotic lesion with calcification at the origin of the renal artery; a CT scan showed atrophy of the left kidney. Renal Doppler ultrasonography was performed and renal resistive indexes were: 0.92 for the left kidney and 0.68 for the right kidney. The viability of the right kidney was thought to be maintained, and percutaneous transluminal renal angioplasty (PTRA) for the right renal artery stenosis was performed; his creatinine level improved (3 mg/dL) and his systolic blood pressure decreased (120 mm Hg). We implanted a stent on the right stenotic lesion and the right renal artery blood flow improved. We experienced an effective PTRA for the right renal artery for bilateral renal artery stenosis. Although the indications of PTRA for renal artery stenosis are limited, the evaluation of renal function using ultrasonography could be a useful index for determining the culprit lesion.

Background: In persistent AF, the effect of adjunctive ablation in addition to PV isolation (PVI) is controversial. We considered a new modified PVI including complex fractionated atrial electrogram (CFAE) area. Methods and Results: In 57 patients with persistent AF undergoing first ablation, CFAE were mapped before ablation and CFAE-guided extensive encircling PVI (CFAE-guided EEPVI) was performed. The PVI line was designed to include the CFAE area near PV or to cross the minimum cycle length points of the CFAE area near PV (CFAE-guided EEPVI group). The outcome was compared with conventional PVI in 34 patients with persistent AF (conventional PVI group). During a mean follow-up of 365±230 days after the first procedure, AF in 13 and atrial tachycardia (AT) in 9 patients recurred in the CFAE-guided EEPVI group, while only AF in 17 patients recurred in the conventional PVI group. Eight of 9 AT in the CFAE-guided EEPVI group were successfully ablated at second procedure. After first and second procedures, the recurrence of atrial tachyarrhythmia in the CFAE-guided EEPVI group was significantly reduced compared with the conventional PVI group (8 patients, 14% vs. 11 patients, 32%, respectively; P

The case of ischemic upper extremity disease caused by guide catheter-induced injury is rare. We present a case of right axillary artery occlusion, after percutaneous coronary intervention (PCI), treated by endovascular stent-grafting successfully.

Background It has previously been reported that oral administration of purified eicosapentaenoic acid (EPA) generates EPA-rich high-density lipoprotein (HDL) particles with a variety of anti-inflammatory properties. In this study, the mechanism underlying the anti-atherogenic effects of EPA-rich HDL using reconstituted HDL (rHDL) was investigated.Methods and Results:rHDL was generated by the sodium cholate dialysis method, using apolipoprotein A-1 protein, cholesterol, and various concentrations of EPA-phosphatidylcholine (PC) or egg-PC. Increased EPA-PC contents in rHDL resulted in decreased particle size. Next, the effects of rHDL containing various amounts (0-100% of total PC) of EPA-PC on vascular cell adhesion molecule-1 (VCAM-1) expression in human umbilical vein endothelial cells (HUVECs) was examined. Cytokine-stimulated VCAM-1 expression was inhibited in a dose-dependent manner based on the amount of EPA-PC in rHDL. Surprisingly, the incubation of HUVECs with EPA-rich rHDL resulted in the production of resolvin E3 (RvE3), an anti-inflammatory metabolite derived from EPA. Incubation with EPA-PC alone did not adequately induce RvE3 production, suggesting that RvE3 production requires an endothelial cell-HDL interaction. The increased anti-inflammatory effects of EPA-rich HDL may be explained by EPA itself and RvE3 production. Furthermore, the increase in EPA-PC content enhanced cholesterol efflux. Conclusions The EPA-enriched HDL particles exhibit cardioprotective properties via the production of anti-inflammatory lipid metabolites and the increase in cholesterol efflux.

Low levels of plasma high-density lipoprotein (HDL) cholesterol are associated with an increased risk of heart failure, regardless of the presence or absence of coronary artery disease. However, the direct effects of HDL on failing myocardium have not been fully elucidated. We found that HDL treatment resulted in improved cell viability in H9c2 cardiomyocytes under oxidative stress. This cardioprotective effect of HDL was regulated via the phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathway. mTOR signaling promotes cell survival through the inactivation of the BCL2-associated agonist of cell death via phosphorylation of ribosomal protein S6 kinase. Modulation of cardiac PI3K/mTOR signaling by HDL could represent a novel therapeutic strategy for heart failure.

A 79-year-old man developed bilateral intermittent claudication. Peritoneal dialysis had been initiated at 55 years of age to manage chronic renal failure. In addition, he underwent kidney transplantation at 61 years of age. His Ankle-Brachial Index (ABI) was 0.82 and 0.71 for the right leg and left leg, respectively. Furthermore, his serum creatinine level had increased from 0.98 mg/dL to 2.38 mg/dL over the past 2 years. CT angiography revealed focal calcified stenosis in the terminal abdominal aorta. However, ultrasound revealed no significant stenotic lesion in the supplied artery bound to the transplanted kidney from the right external iliac artery. We performed endovascular therapy for abdominal aortic stenosis using the pressure gradient. Following the procedure, the patient’s symptoms disappeared and the ABI increased to 1.25 and 1.14 in the right leg and left leg, respectively. Furthermore, the serum creatinine level improved to 0.96 mg/dL.

Aim: Clinical trials suggest that residual risks remain for coronary artery disease (CAD) during low-density lipoprotein cholesterol (LDL-C) lowering therapy. We aimed to investigate the role of exogenous lipids in the prognosis of CAD after percutaneous coronary intervention (PCI). Methods: A total of 145 patients with CAD, who underwent elective PCI, and 82 non-CAD (control) patients were enrolled in this study. CAD patients underwent follow-up coronary angiography 6–9 months after PCI, and were classified into three groups: 1) patients who showed in-stent restenosis (ISR) in the original stented segment, 2) patients with other non-target coronary atherosclerotic lesions (de novo), and 3) patients with neither ISR nor a de novo lesion. Biochemical analyses were performed on fasting serum samples at the time of follow-up coronary angiography. Results: Despite the controlled serum LDL-C levels, CAD patients with statin showed elevated cholesterol absorption marker campesterol/total cholesterol (TC), synthesis marker lathosterol/TC, campesterol/lathosterol ratio, and apolipoprotein B48 (apoB48) concentration compared with non-CAD patients. The high campesterol/TC, campesterol/lathosterol ratio, and apoB48 concentration were associated with de novo lesion progression after PCI. In stepwise multivariate logistic regression analysis, campesterol/TC and apoB48 concentrations were independent risk factors for de novo lesion progression in statin-treated CAD patients after PCI. Conclusion: The increase of cholesterol absorption marker and apoB48 concentration may lead to the progression of de novo lesions, and these markers may represent a residual risk during statin treatment after PCI.

Patient Initials or Identifier Number 300326626 ### Relevant Clinical History and Physical Exam A 71-year-old female had SFA-PTA bypass surgery planned for chronic limb ischemia. Her comorbidities were hypertension and chronic kidney disease with hemodialysis. At clinical examination, her

Neoatherosclerosis is the major cause of late-phase target lesion revascularization (TLR) after stent implantation. We assessed the effect of lipid-lowering therapy with rosuvastatin 10 mg/day and eicosapentaenoic acid (EPA) 1800 mg/day on in-stent neoatherosclerosis using optical coherence

Objective: Myeloperoxidase (MPO) is known as major leukocyte enzyme that oxidizes lipoproteins. High density lipoprotein (HDL) contains paraoxonase 1 (PON1), which hydrolyzes oxidized phospholipids. HDL requires PON1 to attenuate accumulation of lipid peroxides in LDL. We recently reported that serum MPO/PON1 ratio could be used as a useful marker for dysfunctional HDL and showed elevated ratios in patients undergoing recurrent percutaneous coronary intervention (PCI). However, it remains obscure whether serum MPO/PON1 ratio can predict relapsing coronary atherosclerotic lesions after PCI. Methods and Results: Total 111 patients who had a history of successful PCI were enrolled. Their serum MPO mass and PON1 activities were measured at the time point of enrollment, and they had angiographical follow-up evaluation. Fourteen patients needed repeat-PCI due to restenosis and/or de novo lesions during the follow up period (143±730 days). With the established cut off value of 1.59 based on our previous work, Kaplan-Meier analysis showed significantly higher recurrence rate of coronary lesions which required PCI treatment in patients with higher MPO/PON1 ratio at enrollment than that in patients with lower MPO/PON1 ratio (66.7% vs. 6.0%, p Conclusions: This study demonstrated that higher MPO/PON1 ratio (>1.59) could predict future recurrence of coronary lesions after PCI. This ratio could be useful marker for secondary prevention of coronary artery disease.

High-density lipoprotein (HDL) interacts with various cells, particularly macrophages, in functional cell-HDL interactions. Here, we found that HDL protein quality and lipid quality play critical roles in HDL functions. HDL fractions from healthy volunteers (HDLHealthy) and patients with recurrent coronary atherosclerotic disease (HDLCAD) were prepared. To analyse functional HDL-macrophage interactions, macrophages were co-incubated with each HDL, and lipid mediator production was assessed by liquid chromatography/mass spectrometry-based metabololipidomics. HDLHealthy treatment attenuated the pro-inflammatory lipid mediator production, particularly that of leukotriene (LT) B4, and this treatment enhanced lipoxin (LX) B4 and resolvin (Rv) E2 production. HDLHealthy treatment enhanced the proteasome-mediated degradation of the LTB4-producing enzyme 5-lipoxygenase (LO) in activated macrophages; however, HDLCAD did not show these anti-inflammatory effects. HDLHealthy was engulfed by macrophages via clathrin-mediated endocytosis, which was a critical step in 5-LO/LTB4 regulation. We also found that HDLCAD showed higher levels of the LTB4-producing enzymes and thus promoted LTB4 production from HDLCAD. In addition, LTB4 attenuated HDL endocytosis, HDL-mediated 5-LO degradation in macrophages, and HDL-derived augmentation of macrophage phagocytosis. These results indicated that local LTB4 produced de novo from HDLCAD regulates HDL-macrophage functional interactions and plays critical roles in dysfunctional, inflammatory HDL characteristics.

A previous report showed that the consumption of glutathione through oxidative stress activates the glutathione synthetic pathway, which is accompanied by production of ophthalmic acid from 2-aminobutyric acid (2-AB). We conducted a comprehensive quantification of serum metabolites using gas chromatography-mass spectrometry in patients with atrial septal defect to find clues for understanding myocardial metabolic regulation, and demonstrated that circulating 2-AB levels reflect hemodynamic changes. However, the metabolism and pathophysiological role of 2-AB remains unclear. We revealed that 2-AB is generated by an amino group transfer reaction to 2-oxobutyric acid, a byproduct of cysteine biosynthesis from cystathionine. Because cysteine is a rate-limiting substrate for glutathione synthesis, we hypothesized that 2-AB reflects glutathione compensation against oxidative stress. A murine cardiomyopathy model induced by doxorubicin supported our hypothesis, i.e., increased reactive oxygen species are accompanied by 2-AB accumulation and compensatory maintenance of myocardial glutathione levels. Intriguingly, we also found that 2-AB increases intracellular glutathione levels by activating AMPK and exerts protective effects against oxidative stress. Finally, we demonstrated that oral administration of 2-AB efficiently raises both circulating and myocardial glutathione levels and protects against doxorubicin-induced cardiomyopathy in mice. This is the first study to demonstrate that 2-AB modulates glutathione homeostasis in the myocardium.