Pulmonary surfactant protein B carried by HDL predicts incident CVD in patients with type 1 diabetes
Atherosclerotic CVD is the major cause of death in patients with type 1 diabetes mellitus (T1DM). Alterations in the HDL proteome have been shown to associate with prevalent CVD in T1DM. We therefore sought to determine which proteins carried by HDL might predict incident CVD in patients with T1DM....
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| Format: | Article |
| Language: | English |
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Elsevier
2022-04-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227522000293 |
| _version_ | 1828472980703805440 |
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| author | Baohai Shao Janet K. Snell-Bergeon Laura L. Pyle Katie E. Thomas Ian H. de Boer Vishal Kothari Jere Segrest William S. Davidson Karin E. Bornfeldt Jay W. Heinecke |
| author_facet | Baohai Shao Janet K. Snell-Bergeon Laura L. Pyle Katie E. Thomas Ian H. de Boer Vishal Kothari Jere Segrest William S. Davidson Karin E. Bornfeldt Jay W. Heinecke |
| author_sort | Baohai Shao |
| collection | DOAJ |
| description | Atherosclerotic CVD is the major cause of death in patients with type 1 diabetes mellitus (T1DM). Alterations in the HDL proteome have been shown to associate with prevalent CVD in T1DM. We therefore sought to determine which proteins carried by HDL might predict incident CVD in patients with T1DM. Using targeted MS/MS, we quantified 50 proteins in HDL from 181 T1DM subjects enrolled in the prospective Coronary Artery Calcification in Type 1 Diabetes study. We used Cox proportional regression analysis and a case-cohort design to test associations of HDL proteins with incident CVD (myocardial infarction, coronary artery bypass grafting, angioplasty, or death from coronary heart disease). We found that only one HDL protein—SFTPB (pulmonary surfactant protein B)—predicted incident CVD in all the models tested. In a fully adjusted model that controlled for lipids and other risk factors, the hazard ratio was 2.17 per SD increase of SFTPB (95% confidence interval, 1.12–4.21, P = 0.022). In addition, plasma fractionation demonstrated that SFTPB is nearly entirely bound to HDL. Although previous studies have shown that high plasma levels of SFTPB associate with prevalent atherosclerosis only in smokers, we found that SFTPB predicted incident CVD in T1DM independently of smoking status and a wide range of confounding factors, including HDL-C, LDL-C, and triglyceride levels. Because SFTPB is almost entirely bound to plasma HDL, our observations support the proposal that SFTPB carried by HDL is a marker—and perhaps mediator—of CVD risk in patients with T1DM. |
| first_indexed | 2024-12-11T05:37:41Z |
| format | Article |
| id | doaj.art-02a720eab7624a9ab69fbaae8aea3b24 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-11T05:37:41Z |
| publishDate | 2022-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-02a720eab7624a9ab69fbaae8aea3b242022-12-22T01:19:14ZengElsevierJournal of Lipid Research0022-22752022-04-01634100196Pulmonary surfactant protein B carried by HDL predicts incident CVD in patients with type 1 diabetesBaohai Shao0Janet K. Snell-Bergeon1Laura L. Pyle2Katie E. Thomas3Ian H. de Boer4Vishal Kothari5Jere Segrest6William S. Davidson7Karin E. Bornfeldt8Jay W. Heinecke9Department of Medicine, University of Washington, Seattle, WA, USA; For correspondence: Baohai Shao.Barbara Davis Center for Diabetes, University of Colorado Denver, Aurora, CO, USADepartment of Pediatrics, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USADepartment of Medicine, University of Washington, Seattle, WA, USADepartment of Medicine, University of Washington, Seattle, WA, USADepartment of Medicine, University of Washington, Seattle, WA, USADepartment of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USACenter for Lipid and Arteriosclerosis Science, Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, OH, USADepartment of Medicine, University of Washington, Seattle, WA, USADepartment of Medicine, University of Washington, Seattle, WA, USAAtherosclerotic CVD is the major cause of death in patients with type 1 diabetes mellitus (T1DM). Alterations in the HDL proteome have been shown to associate with prevalent CVD in T1DM. We therefore sought to determine which proteins carried by HDL might predict incident CVD in patients with T1DM. Using targeted MS/MS, we quantified 50 proteins in HDL from 181 T1DM subjects enrolled in the prospective Coronary Artery Calcification in Type 1 Diabetes study. We used Cox proportional regression analysis and a case-cohort design to test associations of HDL proteins with incident CVD (myocardial infarction, coronary artery bypass grafting, angioplasty, or death from coronary heart disease). We found that only one HDL protein—SFTPB (pulmonary surfactant protein B)—predicted incident CVD in all the models tested. In a fully adjusted model that controlled for lipids and other risk factors, the hazard ratio was 2.17 per SD increase of SFTPB (95% confidence interval, 1.12–4.21, P = 0.022). In addition, plasma fractionation demonstrated that SFTPB is nearly entirely bound to HDL. Although previous studies have shown that high plasma levels of SFTPB associate with prevalent atherosclerosis only in smokers, we found that SFTPB predicted incident CVD in T1DM independently of smoking status and a wide range of confounding factors, including HDL-C, LDL-C, and triglyceride levels. Because SFTPB is almost entirely bound to plasma HDL, our observations support the proposal that SFTPB carried by HDL is a marker—and perhaps mediator—of CVD risk in patients with T1DM.http://www.sciencedirect.com/science/article/pii/S0022227522000293SFTPBHDL proteomicsincident CVDMSparallel reaction monitoringCACTI |
| spellingShingle | Baohai Shao Janet K. Snell-Bergeon Laura L. Pyle Katie E. Thomas Ian H. de Boer Vishal Kothari Jere Segrest William S. Davidson Karin E. Bornfeldt Jay W. Heinecke Pulmonary surfactant protein B carried by HDL predicts incident CVD in patients with type 1 diabetes Journal of Lipid Research SFTPB HDL proteomics incident CVD MS parallel reaction monitoring CACTI |
| title | Pulmonary surfactant protein B carried by HDL predicts incident CVD in patients with type 1 diabetes |
| title_full | Pulmonary surfactant protein B carried by HDL predicts incident CVD in patients with type 1 diabetes |
| title_fullStr | Pulmonary surfactant protein B carried by HDL predicts incident CVD in patients with type 1 diabetes |
| title_full_unstemmed | Pulmonary surfactant protein B carried by HDL predicts incident CVD in patients with type 1 diabetes |
| title_short | Pulmonary surfactant protein B carried by HDL predicts incident CVD in patients with type 1 diabetes |
| title_sort | pulmonary surfactant protein b carried by hdl predicts incident cvd in patients with type 1 diabetes |
| topic | SFTPB HDL proteomics incident CVD MS parallel reaction monitoring CACTI |
| url | http://www.sciencedirect.com/science/article/pii/S0022227522000293 |
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