Pulmonary surfactant protein B carried by HDL predicts incident CVD in patients with type 1 diabetes

Area of Science:

• Cardiovascular Science
• Metabolic Disorders
• Proteomics

Background:

• Atherosclerotic cardiovascular disease (CVD) is a leading cause of mortality in type 1 diabetes mellitus (T1DM).
• Alterations in high-density lipoprotein (HDL) proteome are linked to prevalent CVD in T1DM.
• Identifying HDL proteins that predict incident CVD in T1DM is crucial for risk stratification.

Purpose of the Study:

• To identify specific proteins within HDL that can predict the occurrence of incident CVD in individuals with T1DM.
• To investigate the association between HDL-bound proteins and future cardiovascular events in a T1DM cohort.

Main Methods:

• Targeted mass spectrometry (MS/MS) was used to quantify 50 proteins in HDL from 181 T1DM subjects.
• Cox proportional regression analysis and a case-cohort design were employed to assess associations with incident CVD.
• Plasma fractionation confirmed the binding of identified proteins to HDL.

Main Results:

• Pulmonary surfactant protein B (SFTPB) was the only HDL protein that significantly predicted incident CVD across all tested models.
• Increased SFTPB levels were associated with a 2.17-fold higher risk of CVD events per standard deviation increase, independent of traditional risk factors.
• SFTPB predicted CVD risk in T1DM patients irrespective of smoking status or lipid profiles (HDL-C, LDL-C, triglycerides).

Conclusions:

• SFTPB, predominantly bound to HDL, serves as a significant predictor of incident CVD in patients with T1DM.
• These findings suggest SFTPB carried by HDL may act as both a marker and a potential mediator of CVD risk in T1DM.
• This research highlights SFTPB as a novel therapeutic target or biomarker for managing cardiovascular risk in T1DM.