Dataset Information

Association between proprotein convertase subtilisin/kexin type 9 and late saphenous vein graft disease after coronary artery bypass grafting: a cross-sectional study.

ABSTRACT:

Objective

The study aims to explore the association between serum proprotein convertase subtilisin/kexin type 9 (PCSK9) level and saphenous vein grafts disease (SVGD) after coronary artery bypass grafting (CABG).

Design

A cross-sectional study.

Setting

A secondary hospital in Tianjin City, China.

Participants

A total of 231 participants were included in the study. Inclusion criteria were as follows: age ?18 years, previous CABG surgery at least 12 months ago, at least one SVG for bypass during CABG, abnormal non-invasive test results or recurrent stable angina pectoris by coronary angiography indications, and willing to participate and sign informed consent. Participants with any of the following were excluded from the study: congenital valvular disease, decompensated heart failure, anaemia defined as a haemoglobin level of <12?g/dL in women or <13?g/dL in men, malignant neoplasms, renal failure, severe hepatic disease, thyroid disease, acute or chronic inflammatory disease and chronic obstructive lung disease.

Primary outcome measure

SVGD was defined as at least one SVG with significant stenosis (?50%). Circulating PCSK9 levels were measured using commercial ELISA kits according to the manufacturer's instructions.

Results

The mean PCSK9 level in the SVGD group was significantly higher than that in the patent group (275.2±38.6 vs 249.3±37.7, p<0.01). The multivariate logistic regression model revealed a significant association between serum PCSK9 and SVGD (OR 2.08, 95% CI 1.46-2.95) per 1 SD increase in serum PCSK9.

Conclusions

The present study is the first to identify an independent association between PCSK9 and late SVGD after adjustment for established cardiovascular risk factors. A multicentre prospective cohort study with large sample size should be conducted in the future to further research this relationship.

SUBMITTER: Gao J

PROVIDER: S-EPMC6089317 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Association between proprotein convertase subtilisin/kexin type 9 and late saphenous vein graft disease after coronary artery bypass grafting: a cross-sectional study.

Gao Jing J Wang Hai-Bo HB Xiao Jian-Yong JY Ren Min M Reilly Kathleen Heather KH Li Yu-Ming YM Liu Yin Y

BMJ open 20180710 7

<h4>Objective</h4>The study aims to explore the association between serum proprotein convertase subtilisin/kexin type 9 (PCSK9) level and saphenous vein grafts disease (SVGD) after coronary artery bypass grafting (CABG).<h4>Design</h4>A cross-sectional study.<h4>Setting</h4>A secondary hospital in Tianjin City, China.<h4>Participants</h4>A total of 231 participants were included in the study. Inclusion criteria were as follows: age ≥18 years, previous CABG surgery at least 12 months ago, at leas ...[more]

PMID: 29991632

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Project description:Proprotein convertase subtilisin/kexins (PCSKs) constitute a family of nine related proteases: PCSK1-7, MBTPS1, and PCSK9. Apart from PCSK9, little is known about PCSKs in cardiovascular disease. Here, we aimed to investigate the expression landscape and druggability potential of the entire PCSK family for CVD. We applied an integrative approach, combining genetic, transcriptomic and proteomic data from three vascular biobanks comprising carotid atherosclerosis, thoracic and abdominal aneurysms, with patient clinical parameters and immunohistochemistry of vascular biopsies. Apart from PCSK4, all PCSK family members lie in genetic regions containing variants associated with human cardiovascular traits. Transcriptomic analyses revealed that FURIN, PCSK5, MBTPS1 were downregulated, while PCSK6/7 were upregulated in plaques vs. control arteries. In abdominal aneurysms, FURIN, PCSK5, PCSK7, MBTPS1 were downregulated, while PCSK6 was enriched in diseased media. In thoracic aneurysms, only FURIN was significantly upregulated. Network analyses of the upstream and downstream pathways related to PCSKs were performed on the omics data from vascular biopsies, revealing mechanistic relationships between this protein family and disease. Cell type correlation analyses and immunohistochemistry showed that PCSK transcripts and protein levels parallel each other, except for PCSK9 where transcript was not detected, while protein was abundant in vascular biopsies. Correlations to clinical parameters revealed a positive association between FURIN plaque levels and serum LDL, while PCSK6 was negatively associated with Hb. PCSK5/6/7 were all positively associated with adverse cardiovascular events. Our results show that PCSK6 is abundant in plaques and abdominal aneurysms, while FURIN upregulation is characteristic for thoracic aneurysms. PCSK9 protein, but not the transcript, was present in vascular lesions, suggesting its accumulation from circulation. Integrating our results lead to the development of a novel 'molecular' 5D framework. Here, we conducted the first integrative study of the proprotein convertase family in this context. Our results using this translational pipeline, revealed primarily PCSK6, followed by PCSK5, PCSK7 and FURIN, as proprotein convertases with the highest novel therapeutic potential.

Dataset Information

Association between proprotein convertase subtilisin/kexin type 9 and late saphenous vein graft disease after coronary artery bypass grafting: a cross-sectional study.

Objective

Design

Setting

Participants

Primary outcome measure

Results

Conclusions

Publications

Association between proprotein convertase subtilisin/kexin type 9 and late saphenous vein graft disease after coronary artery bypass grafting: a cross-sectional study.

Similar Datasets

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