Protective Effect of Flavonoids from a Deep-Sea-Derived Arthrinium sp. against ox-LDL-Induced Oxidative Injury through Activating the AKT/Nrf2/HO-1 Pathway in Vascular Endothelial Cells.

Oxidized low-density lipoprotein (ox-LDL)-induced oxidative injury in vascular endothelial cells is crucial for the progression of cardiovascular diseases, including atherosclerosis. Several flavonoids have been shown cardiovascular protective effects. Recently, our research group confirmed that the novel flavonoids isolated from the deep-sea-derived fungus Arthrinium sp., 2,3,4,6,8-pentahydroxy-1-methylxanthone (compound 1) and arthone C (compound 2) effectively scavenged ROS in vitro. In this study, we further investigated whether these compounds could protect against ox-LDL-induced oxidative injury in endothelial cells and the underlying mechanisms. Our results showed that compounds 1 and 2 inhibited ox-LDL-induced apoptosis and adhesion factors expression in human umbilical vein vascular endothelial cells (HUVECs). Mechanistic studies showed that these compounds significantly inhibited the ROS level increase and the NF-κB nuclear translocation induced by ox-LDL. Moreover, compounds 1 and 2 activated the Nrf2 to transfer into nuclei and increased the expression of its downstream antioxidant gene HO-1 by inducing the phosphorylation of AKT in HUVECs. Importantly, the AKT inhibitor MK-2206 2HCl or knockdown of Nrf2 by RNA interference attenuated the inhibition effects of these compounds on ox-LDL-induced apoptosis in HUVECs. Meanwhile, knockdown of Nrf2 abolished the effects of the compounds on ox-LDL-induced ROS level increase and the translocation of NF-κB to nuclei. Collectively, the data showed that compounds 1 and 2 protected endothelial cells against ox-LDL-induced oxidative stress through activating the AKT/Nrf2/HO-1 pathway. Our study provides new strategies for the design of lead compounds for related cardiovascular diseases treatment.

Secondhand Smoke Exposure in Aging-related Cardiac Disease.

Exposure to secondhand smoke (SHS) exposure is increased the risk of heart disease included atherosclerosis and coronary disease. Aging is a physiology process involving progressive impairment of normal heart functions, due to an increasing vulnerability, which reduces the ability of survive. However, it is not clear pathological condition in aging exposure to SHS. The aim of this study was to examine SHS exposure in aging-related disease. The rats were placed in SHS exposure chamber and exposed to 10 cigarettes for 30 min, twice a day, 5 days/ one week for 1 month. After 4 weeks secondhand smoke exposure, rats left ventricular (LV) underwent morphological and function study with echocardiography. Histopathology of left ventricular sections were stained with Hematoxylin-Eosin staining and related left ventricular hypertrophy protein expression levels by Western blot analysis. After 4 weeks SHS exposure, LV weight showed significant increased. On the other hand, from echocardiography result, we found EF (%) and FS (%) were apparently decreased in aging SHS exposure. IVS, LVID and LVPW at diastolic diameters were increased in aging SHS exposure. However, in aging systolic diameters always preserved. Here we did not show that. Moreover, we observed enlargement morphology of the LV and LV well thickness of increase. In addition, we found LV hypertrophy marker protein, calcineurin/NFATc4, was only increased in aging and aging SHS exposure. Our study suggests that SHS exposure and aging will altercate left ventricular hypertrophy.