The Proteome Profile of Stress Test Assessed Cardiovascular Disease Risk-Prone Diabetic Subjects

Area of Science:

• Biochemistry
• Proteomics
• Cardiovascular Medicine

Background:

• Cardiovascular disease (CVD) is the primary cause of mortality in individuals with diabetes.
• Accurate prediction of CVD risk in diabetics requires specific and reliable biomarkers.
• Current methods like the treadmill test (TMT) have limitations in assessing CVD risk.

Purpose of the Study:

• To identify novel plasma protein biomarkers for assessing cardiovascular disease (CVD) risk in diabetic individuals.
• To compare plasma proteome profiles of diabetic stress test positive (DSTP) and diabetic stress test negative (DSTN) subjects.
• To validate potential CVD biomarkers using targeted mass spectrometry.

Main Methods:

• Utilized SWATH-MS-based label-free quantitative mass spectrometry to analyze plasma proteomes.
• Identified differentially expressed proteins (DEPs) between DSTP and DSTN groups.
• Validated key CVD-relevant DEPs using targeted mass spectrometry (MRM-HR) and ROC analysis.

Main Results:

• Identified CO4B, PON1, and LUM as significantly differentially expressed proteins in diabetic subjects with varying CVD risk.
• Achieved significant area under the curve (AUC) values of 0.97 for CO4B, 0.79 for PON1, and 0.77 for LUM via ROC analysis.
• Demonstrated consistent differential expression of these proteins across both quantitative mass spectrometry approaches.

Conclusions:

• CO4B, PON1, and LUM are proposed as potential alternative biomarkers for assessing CVD risk in the diabetic population.
• These identified proteins may help overcome the limitations associated with traditional treadmill testing (TMT).
• Further validation in larger cohorts is recommended to confirm the clinical utility of these novel biomarkers.