Ubiquitination is a representative, reversible biological process of the post-translational modification of various proteins with multiple catalytic reaction sequences, including ubiquitin itself, in addition to E1 ubiquitin activating enzymes, E2 ubiquitin conjugating enzymes, E3 ubiquitin ligase, deubiquitinating enzymes, and proteasome degradation. The ubiquitin–proteasome system is known to play a pivotal role in various molecular life phenomena, including the cell cycle, protein quality, and cell surface expressions of ion-transporters. As such, the failure of this system can lead to cancer, neurodegenerative diseases, cardiovascular diseases, and hypertension. This review article discusses Nedd4-2/NEDD4L, an E3-ubiquitin ligase involved in salt-sensitive hypertension, drawing from detailed genetic dissection analysis and the development of genetically engineered mice model. Based on our analyses, targeting therapeutic regulations of ubiquitination in the fields of cardio-vascular medicine might be a promising strategy in future. Although the clinical applications of this strategy are limited, compared to those of kinase systems, many compounds with a high pharmacological activity were identified at the basic research level. Therefore, future development could be expected.

Background: Recently, the arterial velocity pulse index (AVI) and arterial pressure volume index (API) have been used to evaluate arterial stiffness and endothelial function. As arterial stiffness and endothelial injury are risk factors for coronary artery disease (CAD), these two indexes are therefore expected to predict and evaluate the future risk of CAD and cardiovascular events before clinical manifestations. Methods: A total of 90 consecutive patients with coronary angiography (CAG) were enrolled. After excluding normal patients and acute coronary syndrome patients, forty-seven patients with CAD and thirty-two patients with coronary atherosclerosis, and baseline characteristics data were collected. A multifunctional blood pressure monitoring device, AVE-1500 (Shisei Datum, Tokyo, Japan), was used to measure the AVI and API before CAG, and immediately and 2 h, 24 h, and 48 h after CAG and (or) PCI in all the selected participants. Results: After adjusting for various variables using stepwise multiple linear regression analyses, we found that the AVI in the CAD subjects was significantly higher than that in the coronary atherosclerosis subjects before CAG (p = 0.02), immediately after CAG/PCI (p = 0.01), and 48 h after CAG/PCI (p = 0.01), whereas the AVI decreased 24–48 h rather than immediately after CAG/PCI in the CAD group. Moreover, we also found that the API clearly changed in both groups during the periprocedural period of CAG (p = 0.01). Conclusions: In accordance with the results, we propose that the API and AVI may be useful for predicting the early stage of CAD and may be promising as indicators to assess the effect of early revascularization.