Advanced Oxidation Protein Products Induce Vascular Calcification by Promoting Osteoblastic Trans-Differentiation of Smooth Muscle Cells via Oxidative Stress and ERK Pathway

Abstract

Vascular calcification is an actively regulated process similar to bone formation. Advanced oxidation protein products (AOPPs) have been demonstrated to be novel markers of oxidantmediated protein damage. The present study investigated the role of AOPPs in inducing osteoblastic trans-differentiation and calcification of smooth muscle cells in vitro. We found that AOPPs directly increased the calcium deposition and expression of core binding factor-a1 (CBF-a1) and osteopontin (OPN) and significantly decreased SM-a-actin expression in human aortic smooth muscle cells (HASMCs). AOPPs increased intracellular oxidative stress, which was inhibited by vitamin E. Vitamin E also inhibited AOPP-induced calcium content and osteoblast differentiation of HASMCs. Furthermore, the inhibitor of ERK significantly suppressed the effects of AOPPs on calcification and osteoblast marker expression. These findings suggest that AOPPs induce vascular calcification by promoting osteoblast differentiation of smooth muscle cells via oxidative stress and ERK pathway.

Metanephros Transplantation Inhibits the Progression of Vascular Calcification in Rats with Adenine-Induced Renal Failure

“…Microinflammation and oxidative stress are also involved in the development of vascular calcification [19,20]. Whether developing metanephroi have antioxidant properties has not been investigated, but serum levels of EPO, which has been reported to have antioxidant effects [21], were increased in the transplanted group in the present study.…”

Palmitic Acid Increases Medial Calcification by Inducing Oxidative Stress

“…More recently, it was also shown that stearate induced cell calcification by inducing ER stress [41]. Since ERK1/2 are part of the ROS downstream mediators and have been previously associated with osteogenic differentiation of VSMC [9,12,14], we evaluated their activation in PA induced calcification. The results obtained in the current study indicate that signaling between oxidative stress and vascular calcification induced by PA involves ERK1/2 activation.…”

“…Downstream, ROS production is known to induce activation of the ERK1/2 pathway [17]. The relevance of ERK1/2 in vascular calcification has been demonstrated by some studies [9,12,14], but is has also been contradicted by others [18,19]. Metabolic abnormalities, such as those found in diabetes and metabolic syndrome, have been associated with enhanced oxidative stress and may represent conditions associated with ROS-induced calcification.…”

“…However, there is evidence showing that oxidative stress can induce osteogenic gene expression leading to calcification of VSMC [11,12,13,14]. Some studies have shown that the activity of NADPH oxidase, a key enzyme in ROS production, is implicated in the expression of osteoblastic gene markers [13,14].…”

Relationship between Aortic Arch Calcification, Detected by Chest X-Ray, and Renal Resistive Index in Patients with Hypertension

“…Vascular calcification is one of the most important indicators of hypertension-related vascular damage. Inflammation, oxidative stress, advanced age, and renin-angiotensin system are important factors involved in the development of vascular calcification [17-19]. Angiotensin 2, the substrate of the renin-angiotensin system, plays an active role in the growth and differentiation of vascular smooth muscle cells [18].…”