The anti-atherosclerotic di-peptide, Trp-His, inhibits the phosphorylation of voltage-dependent L-type Ca ²⁺ channels in rat vascular smooth muscle cells

Trp-His is the only vasoactive di-peptide known to regulate intracellular Ca ²⁺ ([Ca ²⁺] _i) and prevent the onset of atherosclerosis in mice. In this study, we showed that Trp-His reduced the [Ca ²⁺] _i elevation in phospholipase C-activated vascular smooth muscle cells (VSMCs), while a mixture of the corresponding constituent amino acids did not show significant reduction. Furthermore, Trp-His suppressed calmodulin-dependent kinase II (CaMK II) activity in angiotensin II-stimulated VSMCs, resulting in the inhibition of phosphorylation of voltage-dependent L-type Ca ²⁺ channels (VDCC). Therefore, Trp-His potentially regulates the VDCC phosphorylation cascade through Ca ²⁺-CaM/CaMK II.