Conjugated linoleic acid improves endothelial Ca2+ signaling by blocking growth factor and cytokine-mediated Cx43 phosphorylation

• Published in: Molecular and cellular endocrinology 2020-06, Vol.510, p.110814-110814, Article 110814
• Main Authors: Mauro, Amanda K., Berdahl, Danielle M., Khurshid, Nauman, Clemente, Luca, Ampey, Amanda C., Shah, Dinesh M., Bird, Ian M., Boeldt, Derek S.
• Format: Article
• Language: English
• Subjects: Ca2; Conjugated linoleic acid; Cytokine; Growth factor; Preeclampsia
• ISSN: 0303-7207; 1872-8057
• DOI: 10.1016/j.mce.2020.110814

Sustained Ca2+ burst signaling is crucial for endothelial vasodilator production and is disrupted by growth factors and cytokines. Conjugated linoleic acid (CLA), a Src inhibitor in certain preparations, is generally regarded as safe during pregnancy by the FDA. Multiple CLA preparations; t10, c12 or c9, t11 CLA, or a 1:1 mixture of the two were administered before growth factor or cytokine treatment. Growth factors and cytokines caused a significant decrease in Ca2+ burst numbers in response to ATP stimulation. Both t10, c12 CLA and the 1:1 mixture rescued VEGF165 or TNFα inhibited Ca2+ bursts and correlated with Src-specific phosphorylation of connexin 43. VEGF165, TNFα, and IL-6 in combination at physiologic concentrations revealed IL-6 amplified the inhibitory effects of lower dose of VEGF165 and TNFα. Again, the 1:1 CLA mixture was most effective at rescue of function. Therefore, CLA formulations may be a promising treatment for endothelial dysfunction in diseases such as preeclampsia. •GF/Cyt, alone or in combination, promote endothelial dysfunction and are rescued by the nutraceutical CLA.•GF/Cyt coupled directly to Src mediate this damage, and is rescued by t10, c12 CLA or a 1:1 mix of c9, t11 and t10, c12 CLA.•Interleukins are less damaging than GFs, and are more resistant to CLA rescue.