Palmitic acid increases medial calcification by inducing oxidative stress

Area of Science:

• Cardiovascular Biology
• Cellular Signaling
• Arterial Physiology

Background:

• Aortic medial calcification contributes to arterial stiffness.
• Epidemiological studies link saturated fatty acids (FA) to arterial stiffness.
• Evidence that saturated FA induce medial calcification is lacking.

Purpose of the Study:

• Investigate palmitic acid (PA) capacity to induce medial calcification.
• Elucidate signaling pathways involved in PA-induced calcification.

Main Methods:

• Exposed rat aortic segments and vascular smooth muscle cells (VSMC) to PA in calcification medium.
• Administered warfarin and a PA-enriched diet to rats in vivo.
• Utilized apocynin and siRNA to inhibit NADPH oxidase; employed ERK1/2 inhibitors.

Main Results:

• Palmitate increased calcification and reactive oxygen species (ROS) production in vitro and ex vivo.
• Palmitate enhanced ERK1/2 phosphorylation and osteogenic gene expression, effects blocked by NADPH oxidase or ERK1/2 inhibition.
• In vivo, PA-enriched diet amplified medial calcification and pulse wave velocity (PWV), mediated by ROS.

Conclusions:

• ROS induction by palmitate triggers ERK1/2 phosphorylation.
• This signaling cascade promotes VSMC osteogenic differentiation, leading to medial calcification.
• PA-induced arterial stiffness is mediated by ROS production.