Palmitic but Not Oleic Acid Induces Pro-Inflammatory Dysfunction of Human Endothelial Cells from Different Vascular Beds In Vitro.

Daria Shishkova, Victoria Markova, Yulia Yurieva, Alexey Frolov, Anastasia Lazebnaya, Maxim Sinitsky, Anna Sinitskaya, Vera Matveeva, Evgenia Torgunakova, Alexander Stepanov, Anna Malashicheva, Asker Khapchaev, Nikita Podkuychenko, Alexander Vorotnikov, Vladimir Shirinsky, Anton Kutikhin

Journal: International journal of molecular sciences 2025;26(24):

PMID: 41465574

Abstract

Palmitic acid (PA) is the most common dietary saturated fatty acid, and is abundant in palm and cottonseed oil, butter, and cheese, whereas oleic acid (OA) is a monounsaturated omega-9 fatty acid found in olive oil. The differences in the cytotoxic and pro-inflammatory effects of PA and OA across endothelial cells (ECs) isolated from different vascular beds have not been investigated in detail. Here, we incubated primary human aortic valve (HAVEC), saphenous vein (HSaVEC), internal thoracic artery (HITAEC), and microvascular (HMVEC) ECs with albumin-bound PA or OA for 24 h and found that PA induced a considerable cytotoxic response, accompanied by an elevated expression of the genes encoding cell adhesion molecules (VCAM1, ICAM1, SELE, and SELP) and pro-inflammatory cytokines (MIF, PTX3, CSF2, CSF3, IL1A, IL6, CCL2, CCL5, CCL20, CSF2, CSF3, CXCL1, CXCL2, CXCL3, CXCL5, CXCL6, CXCL8, and CXCL10), followed by an increased release of interleukin-6 and interleukin-8. HAVEC and HSaVEC were more susceptible to PA, whereas OA had mild-to-moderate cytotoxic effects on HAVEC and HMVEC but did not induce generalized EC activation. Compared with other EC types, HITAEC was the most resistant to PA and OA treatment. Collectively, these results indicate considerable heterogeneity across the ECs of distinct origin in response to PA.

Address: Department of Experimental Medicine, Research Institute for Complex Issues of Cardiovascular Diseases, 6 Barbarash Boulevard, 650002 Kemerovo, Russia.; Laboratory of Regenerative Biomedicine, Institute of Cytology of the RAS, 4 Tikhoretskiy Prospekt, 194064 St. Petersburg, Russia.; Laboratory for Cell Motility, Institute of Experimental Cardiology, National Medical Research Centre of Cardiology Named After Academician E.I. Chazov, 15A Academician Chazov Street, 121552 Moscow, Russia.
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