Detection of aspartyl aminopeptidase in atherosclerosis mice and clinical sample using an optical probe

TL;DR

This study develops a new optical probe to detect an enzyme linked to atherosclerosis in mice and human samples, offering potential for improved diagnosis.

Contribution

A novel optical probe (HD-DNPEP) for sensitive and specific detection of DNPEP in atherosclerosis.

Findings

HD-DNPEP shows high selectivity and pH stability for DNPEP detection in physiological conditions.

Elevated DNPEP levels were detected in foam cells and cerebrospinal fluid of atherosclerosis patients.

The probe was validated in cells, atherosclerosis mice, and human clinical samples.

Abstract

Atherosclerosis (AS) remains a major global health concern, contributing significantly to cardiovascular morbidity and mortality. Recent research into enzymes like aspartyl aminopeptidase (DNPEP) has shed light on its potential role in regulating inflammation and protein metabolism, offering new avenues for targeted diagnostics and therapies. In light of these challenges, this study aims to develop a novel optical imaging probe (HD-DNPEP) specifically designed to detect DNPEP expression in atherosclerotic lesions. By addressing the current limitations in sensitivity, specificity, and in vivo detection, we seek to create a highly selective and sensitive imaging tool that can provide real-time, high-resolution insights into the role of DNPEP in atherosclerosis. This innovative approach has the potential in the diagnosis of atherosclerosis, enabling more precise intervention strategies and improving patient outcomes. In AS patients, the significantly higher DNPEP levels in the cerebral vasculature and CSF of AS patients suggest that DNPEP may serve as an important biomarker for detecting cerebrovascular arteriosclerosis.

The HD-DNPEP optical probe enables sensitive, real-time detection of DNPEP—a potential atherosclerosis biomarker—via turn-on fluorescence/PA signals, validated in cells, AS mice, and human clinical samples with high selectivity and biosafety, offering translational diagnostic potential.Image 1

•Novel optical probe (HD-DNPEP) developed for sensitive, specific detection of aspartyl aminopeptidase.•"Turn-on" fluorescence and photoacoustic (PA) signals.•High selectivity and pH stability: HD-DNPEP responds selectively to DNPEP in physiological conditions.•Cellular and in vivo validation: Detects elevated DNPEP in foam cells (correlating with lipid accumulation).•Clinical relevance: Confirmed significantly higher DNPEP levels in cerebrospinal fluid (CSF).

Novel optical probe (HD-DNPEP) developed for sensitive, specific detection of aspartyl aminopeptidase.

"Turn-on" fluorescence and photoacoustic (PA) signals.

High selectivity and pH stability: HD-DNPEP responds selectively to DNPEP in physiological conditions.

Cellular and in vivo validation: Detects elevated DNPEP in foam cells (correlating with lipid accumulation).

Clinical relevance: Confirmed significantly higher DNPEP levels in cerebrospinal fluid (CSF).

Figures