Panhypopituitarism Mimicking Acute Coronary Syndrome.

A 59-year-old man suspected of having myocardial infarction with sinus bradycardia, a decreased blood pressure, and ST-change on an electrocardiogram was referred to our hospital's emergency department. Emergent coronary angiography revealed no significant findings. However, the patient experienced shock and required intensive care. Curiosity rose when his urination volume was not disturbed; we suspected hormonal abnormalities. A hormonal examination and imaging analysis revealed panhypopituitarism caused by a Rathke's cyst. Appropriate hormonal replacement therapy improved his symptoms and led to normalization of his electrocardiogram findings. Acute coronary syndrome (ACS) is a fatal disease; however, clinicians must not discount panhypopituitarism, as it may mimic ACS symptoms.

Nontraumatic bladder rupture: The images before and after.

We should consider the complication of bladder rupture for patients with worsened abdominal pain and inability to pass urine following acute cystitis. A CT scan is a useful first-line modality when evaluating for a suspected bladder rupture.

Association of cholesterol uptake capacity, a novel indicator for HDL functionality, and coronary plaque properties: An optical coherence tomography-based observational study.

BACKGROUND: Cholesterol efflux from atherosclerotic lesion is a key function of high-density lipoprotein (HDL). Recently, we established a simple, high-throughput, cell-free assay to evaluate the capacity of HDL to accept additional cholesterol, which is herein referred to as "cholesterol uptake capacity (CUC)". OBJECTIVE: To clarify the cross-sectional relationship between CUC and coronary plaque properties. METHODS: We enrolled 135 patients to measure CUC and assess the morphological features of angiographic stenosis by optical coherence tomography (OCT). We estimated the extent of the lipid-rich plaque by multiplying the mean lipid arc by lipid length (lipid index). The extent of the OCT-detected macrophage accumulation in the target plaque was semi-quantitatively estimated using a grading system. RESULTS: Lipid-rich plaque lesions were identified in 125 patients (92.6%). CUC was inversely associated with the lipid index (R = -0.348, P < 0.0001). In addition, CUC was also inversely associated with macrophage score (R = -0.327, P < 0.0001). Conversely, neither circulating levels of HDL cholesterol nor apoA1 showed a similar relationship. CONCLUSIONS: We demonstrated that CUC was inversely related to lipid-rich plaque burden and the extent of macrophage accumulation, suggesting that CUC could be useful for cardiovascular risk stratification.

Impaired Cholesterol-Uptake Capacity of HDL Might Promote Target-Lesion Revascularization by Inducing Neoatherosclerosis After Stent Implantation.

Background We evaluated the importance of high-density lipoprotein (HDL) functionality for target-lesion revascularization in patients treated with coronary stents using a rapid cell-free assay system to evaluate the functional capacity of HDL to accept additional cholesterol (cholesterol-uptake capacity; CUC). Methods and Results From an optical coherence tomography (OCT) registry of patients treated with coronary stents, 207 patients were enrolled and their HDL was functionally evaluated by measuring the CUC. Follow-up OCT was performed (median duration, 24.5 months after stenting) to evaluate the presence of neoatherosclerosis. Clinical follow-up was performed to assess target-lesion revascularization for a median duration of 42.3 months after stent implantation. Neoatherosclerosis was identified in 37 patients (17.9%). Multivariate logistic regression analysis revealed that a decreased CUC was independently associated with neoatherosclerosis (odds ratio, 0.799; P<0.001). The CUC showed a significant inverse correlation with incidence of target-lesion revascularization (odds ratio, 0.887; P=0.003) and with lipid accumulation inside stents, suggesting that neoatherosclerosis contributes to the association between CUC and target-lesion revascularization. Conclusions Impaired HDL functionality, detected as decreased CUC, might lead to future stent failure by provoking atherogenic changes of the neointima within stents. Both quantitative and qualitative assessments of HDL might enable the improved prediction of clinical outcomes after stent implantation.

Elevated Serum Elaidic Acid Predicts Risk of Repeat Revascularization After Percutaneous Coronary Intervention in Japan.

BACKGROUND: Trans-fatty acid (TFA) intake increases the risk of coronary artery disease (CAD). Our previous cross-sectional survey showed that middle-aged patients with CAD in Japan have elevated serum TFA. In this study, we longitudinally investigated whether elevated TFA is a risk factor in the secondary prevention of CAD for the same-age patients. Methods and Results: A total of 112 patients (age, 21-66 years) who underwent percutaneous coronary intervention were followed up for up to 2 years. Serum elaidic acid was measured using gas chromatography/mass spectrometry as a marker of TFA intake and divided into quartiles. The primary endpoint was ischemia-driven target lesion revascularization (TLR). The hazard ratio (HR) for TLR increased significantly with higher serum elaidic acid (P<0.01). The significant positive trend remained unchanged after adjusting for conventional lipid profile and bare-metal stent usage. In contrast, although triglycerides and low-density lipoprotein cholesterol were positively correlated with elaidic acid, they were not associated with TLR. On multivariable Cox proportional hazard analysis, elevated elaidic acid was independently associated with TLR risk after adjusting for conventional coronary risks (HR, 10.7, P<0.01). CONCLUSIONS: Elevated elaidic acid is associated with higher TLR rate in middle-aged patients with CAD, suggesting that excessive TFA intake is becoming a serious health problem in Japan.

Eicosapentaenoic Acid-Enriched High-Density Lipoproteins Exhibit Anti-Atherogenic Properties.

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.

Novel mechanism of regulation of the 5-lipoxygenase/leukotriene B4 pathway by high-density lipoprotein in macrophages.

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.

High-density lipoprotein protects cardiomyocytes from oxidative stress via the PI3K/mTOR signaling pathway.

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.

Targeted Disruption of JCAD (Junctional Protein Associated With Coronary Artery Disease)/KIAA1462, a Coronary Artery Disease-Associated Gene Product, Inhibits Angiogenic Processes In Vitro and In Vivo.

OBJECTIVE: Recent genome-wide association studies newly identified the human KIAA1462 gene as a new locus for coronary artery disease. However, the function of the gene product, named JCAD (junctional protein associated with coronary artery disease), is unknown. Because JCAD is expressed at cell-cell junctions in endothelial cells, we hypothesized and tested whether JCAD regulates angiogenic processes in vitro and in vivo. APPROACH AND RESULTS: Cell culture experiments revealed impaired angiogenic ability (proliferation, migration, and cord formation) by the knockdown of JCAD with siRNA (P<0.05 versus control siRNA). We have generated mice lacking JCAD (mKIAA1462-/-) by gene-targeted deletion of JCAD to address in vivo angiogenic function. mKIAA1462-/- mice did not show morphological differences in development of retinal vasculature. Ex vivo aortic ring model demonstrated impaired neovascularization in aorta from mKIAA1462-/- mice than control wild-type mice (P<0.05). Tumor growth was assessed by monitoring tumor volume after the subcutaneous injection of melanoma, LLC (Lewis lung carcinoma), and E0771 cells into the mice. mKIAA1462-/- mice exhibited significantly smaller tumor volume compared with wild-type mice (P<0.001). Histological assessment of the tumor exhibited less smooth muscle actin-positive neovascularization determined by CD31-positive vascular structure in tumor of mKIAA1462-/- mice than wild-type mice, indicating that knockdown of JCAD inhibited the vascular maturation in pathological angiogenic process. CONCLUSIONS: These in vitro and in vivo studies suggest that JCAD has a redundant functional role in physiological angiogenesis but serves a pivotal role in pathological angiogenic process after birth.

Enhanced Impact of Cholesterol Absorption Marker on New Atherosclerotic Lesion Progression After Coronary Intervention During Statin Therapy.

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.