p53 and Vascular Dysfunction: MicroRNA in Endothelial Cells

In many cancer cells, p53 gene is mutated and accumulated, which is considered as a mechanistical target of tumorigenesis. The role of p53 in non-cancerous cells has been focused on, since p53 activation diversely affects as human diseases, including vascular dysfunctions. p53 regulates vascular events, including vascular inflammation and senescence as well as cardiac dysfunction. Many researchers also have paid attention to the role of noncoding RNAs (ncRNAs), especially small-sized microRNAs (miRNAs) for the last decade and their noble biological cellular functions have been discovered. miRNAs expressed in endothelial cells (endothelial miRNAs) have been shown to control vascular events. Firstly, the importance of p53 in a variety of vascular events, such as vascular inflammation and senescence, are summarized. Secondly, the way to regulate miRNAs by p53 and the involvement of miRNAs on p53 function are demonstrated. Finally, several endothelial miRNAs that have important roles are focused on. The aim of this chapter is to understand the role of p53 in vascular diseases in the view of endothelial cell biology and the contribution of miRNAs related to p53

The Role of miRNAs in Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a genetic heterogeneous disease with high mortality and poor prognosis. IPF is characterized by persistent fibroblasts and relentless accumulation of collagen matrix. Epithelial-mesenchymal transition (EMT) and endothelial-to-mesenchymal transition (EndoMT) contribute to the progression of the fibrotic process. There are some therapeutic drugs that delay this progress, but eradicative medicine does not exist yet. MicroRNAs (miRNAs) are short single-stranded RNAs that regulate posttranscriptional silencing. Recent reports have shown that miRNAs play important roles in the development of IPF, as different expression levels of miRNAs in blood and lung tissue from IPF patients were closely associated with the occurrence of IPF disease. In this chapter, we will discuss the role of miRNAs in the pathogenesis, diagnosis, and treatment of IPF. In particular, we will focus on the regulation of EMT/EndoMT by miRNAs

Cepharanthine triggers apoptosis in a human hepatocellular carcinoma cell line (HuH-7) through the activation of JNK1/2 and the downregulation of Akt

AbstractCepharanthine (CEP), a biscoclaurine alkaloid, has been reported to induce cell death, however, the molecular mechanism of this phenomenon remains unclear. We herein report that CEP induced apoptosis in HuH-7 cells through nuclear fragmentation, DNA ladder formation, cytochrome c release, caspase-3 activation and poly-(ADP-ribose)-polymerase cleavage. CEP triggered the generation of reactive oxygen intermediates, the activation of mitogen activated protein kinase (MAPK) p38, JNK1/2 and p44/42, and the downregulation of protein kinase B/Akt. Antioxidants and SP600125, an inhibitor of JNK1/2, but not inhibitors of p38 MAPK and MEK1/2, significantly prevented cell death, thus implying that reactive oxygen species and JNK1/2 play crucial roles in the CEP-induced apoptosis of HuH-7 cells

Endothelial Cell Aging: How miRNAs Contribute?

Endothelial cells (ECs) form monolayers and line the interior surfaces of blood vessels in the entire body. In most mammalian systems, the capacity of endothelial cells to divide is limited and endothelial cells are prone to be senescent. Aging of ECs and resultant endothelial dysfunction lead to a variety of vascular diseases such as atherosclerosis, diabetes mellites, hypertension, and ischemic injury. However, the mechanism by which ECs get old and become senescent and the impact of endothelial senescence on the vascular function are not fully understood. Recent research has unveiled the crucial roles of miRNAs, which are small non-coding RNAs, in regulating endothelial cellular functions, including nitric oxide production, vascular inflammation, and anti-thromboformation. In this review, how senescent-related miRNAs are involved in controlling the functions of ECs will be discussed

The diagnostic value of endothelial function as a potential sensor of fatigue in health

Yoshiko Ohno1,2, Teruto Hashiguchi1, Ryuichi Maenosono1, Hidetoshi Yamashita3, Yukio Taira3, Kazufumi Minowa3, Yoshihito Yamashita3, Yuko Kato3, Ko-ichi Kawahara1, Ikuro Maruyama11Department of Laboratory and Vascular Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima City, Kagoshima Prefecture, Japan; 2Department of Community Health Nursing/Nursing Informatics, School of Health Sciences, Faculty of Medicine, Kagoshima University, Kagoshima City, Kagoshima Prefecture, Japan; 3Kagoshima Seikyo General Hospital, Kagoshima City, Kagoshima Prefecture, JapanPurpose: Many epidemiological research studies have shown that vital exhaustion and psychosocial factors are associated with the occurrence of cerebrocardiovascular disease (CCVD). Fatigue is thought to induce endothelial dysfunction and may be linked to the occurrence of CCVD; however, no studies have investigated this potential link. We studied to determine the effect of fatigue on endothelial function in healthy subjects with no traditional CCVD risk factors or potential confounding factors to be controlled.Subjects and methods: Peripheral arterial tonometry (PAT) was used to evaluate endothelial function. The influence of the following parameters on endothelial function was analyzed in 74 office workers without traditional CCVD risk factors at health check-ups: endothelial function before and after work, subjective fatigue, lifestyle factors such as sleeping time, and psychosocial factors such as depression and social support.Results: Twenty-five subjects (33.8%) had low endothelial function; reactive hyperemia (RH)-PAT index <1.67, even though no abnormalities were reported in the health check-ups. There was no significant difference in endothelial function before versus after labor. Of note, endothelial function was associated with the individual’s level of subjective fatigue (t = 2.98, P = 0.008) and showed a daily fluctuation, sometimes to a pathological degree (<1.67).Conclusion: We showed that, even in healthy people, endothelial function fluctuates diurnally, with an interaction between the individual’s cognitive fatigue and the environment, sometimes to a pathological degree. Based on these findings, we suggest that endothelial function is an objective assessment tool of fatigue in healthy individuals.Keywords: cerebrocardiovascular disease, endothelial dysfunction, subjective fatigue, flow-mediated dilatation, health education, reactive hyperemia peripheral arterial tonometr