Intracoronary Imaging, Cholesterol Efflux, and Transcriptomics after Intensive Statin Treatment in Diabetes
Abstract Residual atherothrombotic risk remains higher in patients with versus without diabetes mellitus (DM) despite statin therapy. The underlying mechanisms are unclear. This is a retrospective post-hoc analysis of the YELLOW II trial, comparing patients with and without DM (non-DM) who received...
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Nature Portfolio
2017
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oai:doaj.org-article:02e1b65f7bc7426a94ade020e84c36882021-12-02T11:40:23ZIntracoronary Imaging, Cholesterol Efflux, and Transcriptomics after Intensive Statin Treatment in Diabetes10.1038/s41598-017-07029-72045-2322https://doaj.org/article/02e1b65f7bc7426a94ade020e84c36882017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07029-7https://doaj.org/toc/2045-2322Abstract Residual atherothrombotic risk remains higher in patients with versus without diabetes mellitus (DM) despite statin therapy. The underlying mechanisms are unclear. This is a retrospective post-hoc analysis of the YELLOW II trial, comparing patients with and without DM (non-DM) who received rosuvastatin 40 mg for 8–12 weeks and underwent intracoronary multimodality imaging of an obstructive nonculprit lesion, before and after therapy. In addition, blood samples were drawn to assess cholesterol efflux capacity (CEC) and changes in gene expression in peripheral blood mononuclear cells (PBMC). There was a significant reduction in low density lipoprotein-cholesterol (LDL-C), an increase in CEC and beneficial changes in plaque morphology including increase in fibrous cap thickness and decrease in the prevalence of thin cap fibro-atheroma by optical coherence tomography in DM and non-DM patients. While differential gene expression analysis did not demonstrate differences in PBMC transcriptome between the two groups on the single-gene level, weighted gene coexpression network analysis revealed two modules of coexpressed genes associated with DM, Collagen Module and Platelet Module, related to collagen catabolism and platelet function respectively. Bayesian network analysis revealed key driver genes within these modules. These transcriptomic findings might provide potential mechanisms responsible for the higher cardiovascular risk in DM patients.Surbhi ChamariaKipp W. JohnsonYuliya VengrenyukUsman BaberKhader ShameerAparna A. DivaraniyaBenjamin S. GlicksbergLi LiSamit BhathejaPedro MorenoAkiko MaeharaRoxana MehranJoel T. DudleyJagat NarulaSamin K. SharmaAnnapoorna S. KiniNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017) |
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Medicine R Science Q Surbhi Chamaria Kipp W. Johnson Yuliya Vengrenyuk Usman Baber Khader Shameer Aparna A. Divaraniya Benjamin S. Glicksberg Li Li Samit Bhatheja Pedro Moreno Akiko Maehara Roxana Mehran Joel T. Dudley Jagat Narula Samin K. Sharma Annapoorna S. Kini Intracoronary Imaging, Cholesterol Efflux, and Transcriptomics after Intensive Statin Treatment in Diabetes |
| description |
Abstract Residual atherothrombotic risk remains higher in patients with versus without diabetes mellitus (DM) despite statin therapy. The underlying mechanisms are unclear. This is a retrospective post-hoc analysis of the YELLOW II trial, comparing patients with and without DM (non-DM) who received rosuvastatin 40 mg for 8–12 weeks and underwent intracoronary multimodality imaging of an obstructive nonculprit lesion, before and after therapy. In addition, blood samples were drawn to assess cholesterol efflux capacity (CEC) and changes in gene expression in peripheral blood mononuclear cells (PBMC). There was a significant reduction in low density lipoprotein-cholesterol (LDL-C), an increase in CEC and beneficial changes in plaque morphology including increase in fibrous cap thickness and decrease in the prevalence of thin cap fibro-atheroma by optical coherence tomography in DM and non-DM patients. While differential gene expression analysis did not demonstrate differences in PBMC transcriptome between the two groups on the single-gene level, weighted gene coexpression network analysis revealed two modules of coexpressed genes associated with DM, Collagen Module and Platelet Module, related to collagen catabolism and platelet function respectively. Bayesian network analysis revealed key driver genes within these modules. These transcriptomic findings might provide potential mechanisms responsible for the higher cardiovascular risk in DM patients. |
| format |
article |
| author |
Surbhi Chamaria Kipp W. Johnson Yuliya Vengrenyuk Usman Baber Khader Shameer Aparna A. Divaraniya Benjamin S. Glicksberg Li Li Samit Bhatheja Pedro Moreno Akiko Maehara Roxana Mehran Joel T. Dudley Jagat Narula Samin K. Sharma Annapoorna S. Kini |
| author_facet |
Surbhi Chamaria Kipp W. Johnson Yuliya Vengrenyuk Usman Baber Khader Shameer Aparna A. Divaraniya Benjamin S. Glicksberg Li Li Samit Bhatheja Pedro Moreno Akiko Maehara Roxana Mehran Joel T. Dudley Jagat Narula Samin K. Sharma Annapoorna S. Kini |
| author_sort |
Surbhi Chamaria |
| title |
Intracoronary Imaging, Cholesterol Efflux, and Transcriptomics after Intensive Statin Treatment in Diabetes |
| title_short |
Intracoronary Imaging, Cholesterol Efflux, and Transcriptomics after Intensive Statin Treatment in Diabetes |
| title_full |
Intracoronary Imaging, Cholesterol Efflux, and Transcriptomics after Intensive Statin Treatment in Diabetes |
| title_fullStr |
Intracoronary Imaging, Cholesterol Efflux, and Transcriptomics after Intensive Statin Treatment in Diabetes |
| title_full_unstemmed |
Intracoronary Imaging, Cholesterol Efflux, and Transcriptomics after Intensive Statin Treatment in Diabetes |
| title_sort |
intracoronary imaging, cholesterol efflux, and transcriptomics after intensive statin treatment in diabetes |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/02e1b65f7bc7426a94ade020e84c3688 |
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