# Programmable Pentamolecular Cross‐Scale Imaging Reveals the Multiplicative Synergistic Effect of High‐Fat / High‐Salt Diet on Atherosclerosis

## TL;DR

This study shows how combining high-fat and high-salt diets worsens atherosclerosis through increased oxidative stress and protein changes.

## Contribution

A new nanosensor array enables cross-scale imaging to reveal synergistic effects of diet on atherosclerosis.

## Key findings

- High-fat and high-salt diets independently cause redox imbalance and elevated protein phosphorylation.
- The combination of high-fat and high-salt diets shows a synergistic effect greater than the sum of individual effects.
- Cross-scale imaging reveals how lifestyle factors accelerate atherosclerosis progression.

## Abstract

Atherosclerosis, as a lipid‐driven chronic inflammatory disease, exhibits close correlation between its early formation and dietary habits, yet lacks closely associated molecular demonstration mechanisms. To address this, we constructed nanosenors for H2O2, HClO, GSH, and AA, achieving cross‐scale fluorescence imaging at cellular, tissue, and in vivo levels for five spectrally distinguishable molecular species through programmed combination of three probe types: oxidative (H2O2, HClO), reductive (GSH, AA), and protein phosphorylation. Using rat models fed with high‐fat, high‐salt, or combined diets, our cross‐scale imaging of oxidative/reductive substances and phosphorylated proteins revealed that both high‐fat and high‐salt diets independently induce redox imbalance in vasculature and organs while significantly elevating protein phosphorylation levels. Notably, the combined high‐fat/high‐salt group demonstrated oxidative stress and protein phosphorylation levels exceeding the additive effects of individual diets (“1+1>2” synergy), unveiling their cooperative acceleration of atherosclerotic progression. This finding provides crucial experimental evidence for understanding the multifactorial synergistic mechanisms whereby lifestyle factors exacerbate oxidative stress and protein phosphorylation in atherosclerosis pathogenesis.

This study demonstrates multifactorial lifestyle impacts on the pathogenesis and progression of cardiovascular diseases by a nanofluorescence sensor array for detecting four redox species and protein phosphorylation levels. Through cross‐scale fluorescence imaging of rats with different diets, we revealed that compared with single dietary interventions, the the high salt and high‐fat combination feeding group exhibited a significant synergistic effect.