👤 Y Yuasa

Plasmalogens are a family of glycerophospholipids containing one vinyl-ether bond at the sn-1 position in the glycerol backbone, and play important roles in cellular homeostasis including neural transmission. Therefore, reductions of plasmalogens have been associated with neurodegenerative disorders, such as Alzheimer's disease (AD). To evaluate the potential protective effects of plasmalogens against the pathology of AD, protein expression levels of key factors in amyloid precursor protein (APP) metabolic processes were examined using human neuroblastoma SH-SY5Y cells. Here, phosphatidylcholine-plasmalogen-oleic acid (PC-PLS-18) was shown to reduce protein expression levels of β-site APP cleaving enzyme 1 (BACE1), clusterin, and Tau, factors involved in the amyloid β-associated pathogenesis of AD. Thus, PC-PLS-18 may have preventive effects against AD by delaying the onset risk for a certain period. Show less

Identifying patients with vulnerable plaque who have poor prognosis among those with coronary artery disease (CAD) is crucial to deciding future therapeutic interventions. We previously reported that male CAD patients with low anti-apolipoprotein B-100 autoantibody (anti-apoB-100 Ab) levels were at an increased risk of developing unstable plaque lesions. This study focused on the autoantibodies against lipoprotein lipase (LPL), a key enzyme in triglyceride metabolism, which is another risk factor for atherosclerosis, and investigated their association with plaque characteristics. We measured serum anti-LPL Ab levels using a homemade enzyme-linked immunosorbent assay in 80 male CAD patients. Coronary plaque properties were evaluated using iMAP Serum anti-LPL Ab levels were not correlated with plaque burden but were significantly negatively and positively correlated with fibrotic and necrotic plaques, respectively. High-risk patients with low anti-apoB-100 Ab levels were divided into groups according to their anti-LPL Ab levels. The group with high anti-LPL Ab levels exhibited more necrotic plaques and fewer fibrotic plaques as well as higher remnant-like lipoprotein particle levels than the group with low anti-LPL Ab levels. Serum anti-LPL Ab levels can serve as a marker of plaque instability in CAD patients and can help identify higher-risk cases when combined with anti-apoB-100 Ab levels. Show less

Despite the accumulating genetic and molecular investigations into hypertrophic cardiomyopathy (HCM), it remains unclear how this condition develops and worsens pathologically and clinically in terms of the genetic-environmental interactions. Establishing a human disease model for HCM would help to elucidate these disease mechanisms; however, cardiomyocytes from patients are not easily obtained for basic research. Patient-specific induced pluripotent stem cells (iPSCs) potentially hold much promise for deciphering the pathogenesis of HCM. The purpose of this study is to elucidate the interactions between genetic backgrounds and environmental factors involved in the disease progression of HCM. We generated iPSCs from 3 patients with HCM and 3 healthy control subjects, and cardiomyocytes were differentiated. The HCM pathological phenotypes were characterized based on morphological properties and high-speed video imaging. The differences between control and HCM iPSC-derived cardiomyocytes were mild under baseline conditions in pathological features. To identify candidate disease-promoting environmental factors, the cardiomyocytes were stimulated by several cardiomyocyte hypertrophy-promoting factors. Interestingly, endothelin-1 strongly induced pathological phenotypes such as cardiomyocyte hypertrophy and intracellular myofibrillar disarray in the HCM iPSC-derived cardiomyocytes. We then reproduced these phenotypes in neonatal cardiomyocytes from the heterozygous Mybpc3-targeted knock in mice. High-speed video imaging with motion vector prediction depicted physiological contractile dynamics in the iPSC-derived cardiomyocytes, which revealed that self-beating HCM iPSC-derived single cardiomyocytes stimulated by endothelin-1 showed variable contractile directions. Interactions between the patient's genetic backgrounds and the environmental factor endothelin-1 promote the HCM pathological phenotype and contractile variability in the HCM iPSC-derived cardiomyocytes. Show less

We previously demonstrated that metastasis-related tumor suppressor gene(s) may exist on chromosome 8p21-22 on allelotype analysis of early colorectal carcinomas (CRC) with lymph node metastasis. Here, we searched for target gene(s) in this chromosomal region in the UniGene database. The EXTL3 (also called EXTR1) gene was selected as a candidate because of its homology to EXT1 and EXT2, putative tumor suppressor genes. We screened 12 CRC cell lines for mutations by means of polymerase chain reaction (PCR)-single strand conformation polymorphism. Three cell lines showed EXTL3 mutations, all of which were located within exon 3 and caused amino acid substitutions. Reverse transcription-PCR analysis showed that the EXTL3 expression was lacking in 1 of the 12 colorectal cancer cell lines. Although there is still no definitive evidence that EXTL3 is a tumor suppressor gene for CRC, these data suggest that inactivation of the EXTL3 gene may at least offer a selective growth advantage for some CRC cell lines. Show less