Metabolite-Affected Interfacial Electrostatics and Its Role in the Pathogenesis of Cardiovascular Disease: An Interface-Selective Vibrational Spectroscopic Study

Cardiovascular disease (CVD) is associated with dietary practices, along with other factors. Metabolism of choline containing diets (e.g., red meat, egg, and various over-the-counter dietary supplements) increases the level of trimethylamine N -oxide (TMAO) in blood, which in turn speeds up the deposition of fat on the inner wall of arteries, making them prone to CVD. Hence, a molecular-level understanding of the TMAO-effect on the fat depositing receptor–ligand interaction at the artery wall–blood interface is essential for the elucidation of the pathogenesis of CVD. Interface-selective and phase-sensitive vibrational spectroscopic study (heterodyne-detected vibrational sum frequency generation, HD-VSFG) of suitable model systems, mimicking the artery wall–blood interface, reveals a surprising charge specific “TMAO-effect” on interfacial electrostatics. The interfacial electric field due to cationic ammonium group embedded in lipid monolayer (mimic of the positively charged domains of lipid-bound receptor/ligand) is strongly screened by TMAO, whereas the interfacial field due to anionic carboxylate in the lipid monolayer (mimic of the negatively charged domains of the lipid-bound receptor/ligand) remains almost unaffected in the presence of TMAO. Altogether, these observations suggest that TMAO (in blood) weakens the receptor–ligand electrostatic interaction at the artery wall–blood interface. As a result, the receptor-mediated removal of fatty deposits (from the artery wall) becomes ineffective, leading to the increased risk of CVD.