Palmitic Acid Increases Medial Calcification by Inducing Oxidative Stress

Abstract

Background: Aortic medial calcification is a cellular-regulated process leading to arterial stiffness. Although epidemiological studies have suggested an association between the saturation of fatty acids (FA) and arterial stiffness, there is no evidence that saturated FA can induce arterial calcification. This study investigated the capacity of palmitic acid (PA) to induce medial calcification and the signaling pathway(s) implicated in this process. Methods: Rat aortic segments and vascular smooth muscle cells (VSMC) were exposed to calcification medium supplemented with PA. In vivo, rats were treated with warfarin to induce calcification and fed a PA-enriched diet. Results: In vitro and ex vivo, palmitate increases calcification and ROS production. Palmitate increases extracellular-signal-regulated kinase (ERK1/2) phosphorylation and osteogenic gene expression. Inhibition of NADPH oxidase with apocynin or an siRNA prevents these effects. ERK1/2 inhibition attenuates the amplification of osteogenic gene expression and calcification induced by palmitate. In vivo, a PA-enriched diet amplified medial calcification and pulse wave velocity (PWV). These effects are mediated by ROS production as indicated by the inhibition of calcification and PWV normalization in rats concomitantly treated with apocynin. Conclusion: ROS induction by palmitate leads to ERK1/2 phosphorylation and subsequently induces the osteogenic differentiation of VSMC.

Cholesterol and fatty acids regulate cysteine ubiquitylation of ACAT2 through competitive oxidation

“…Cholesterol and oxysterols could cause mitochondria dysfunction and ROS production 3, 4 . Saturated fatty acids, but not unsaturated fatty acids, also efficiently induce ROS generation through activating NADPH oxidation and mitochondrial electron transport 5, 6 . However, how cells sense and adapt to lipid overload-induced oxidative stress remains elusive.…”

Apocynin attenuates angiotensin II-induced vascular smooth muscle cells osteogenic switching via suppressing extracellular signal-regulated kinase 1/2

“…However, the potential mechanisms are not clear. Although Brodeur et al found that downregulating the osteogenic mRNA expression of cbfa1, alkaline phosphatase and osteocalcin was associated with the beneficial effects of apocynin on VC [27], the mechanisms between apocynin and VSMCs phenotypic switching have not been further explored. In this work, we paid more attention to how apocynin affected VSMCs switching from a contractile to osteogenic phenotype.…”

Perturbations in fatty acid metabolism and apoptosis are manifested in calcific coronary artery disease: An exploratory lipidomic study

“…3). It has been previously suggested that the unsaturated fatty acid stearate [12,39] and -to a lesser extentpalmitate [39,40] can induce calcification in vascular smooth muscle cells. However, this is not the case with monounsaturated 18C chains, which have been previously shown to demonstrate the opposite or no effect [12].…”