Author + information
- Received November 7, 2018
- Revision received May 23, 2019
- Accepted May 23, 2019
- Published online September 23, 2019.
- Joshua A. Beckman, MDa,
- Sean P. Doherty, BAa,
- Zachary B. Feldman, BAa,
- Emily S. Banks, BSa,
- Javid Moslehi, MDa,
- Iris Z. Jaffe, MD, PhDb,
- Naomi M. Hamburg, MDc,
- Quanhu Sheng, PhDd and
- Jonathan D. Brown, MDa,∗ ()
- aDivision of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
- bMolecular Cardiology Research Institute, Tufts Medical Center, Boston, Massachusetts
- cEvans Department of Medicine and Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts
- dCenter for Quantitative Sciences, Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, Tennessee
- ↵∗Address for correspondence:
Dr. Jonathan D. Brown, Vanderbilt University Medical Center, 2220 Pierce Avenue, Preston Research Building, Suite 383, Nashville, Tennessee 37232.
• Endothelial cells can be harvested directly from humans, rapidly sorted and subjected to RNA-sequencing to study global gene expression.
• In endothelial cells isolated from patients with type 2 diabetes mellitus, pathways involved in TGF-β and Cyclin-D1 signaling were positively enriched while androgen signaling and oxidative phosphorylation were negatively enriched compared to healthy individuals.
• Patient-derived endothelial cells can be used to discover and validate disease-associated pathways.
In this study low-input RNA-sequencing was used to annotate the molecular identity of endothelial cells isolated and immunopurified with CD144 microbeads. Using this technique, comparative gene expression profiling from healthy subjects and patients with type 2 diabetes mellitus identified both known and novel pathways linked with EC dysfunction. Modeling of diabetes by treating cultured ECs with high glucose identified shared changes in gene expression in diabetic cells. Overall, the data demonstrate how purified ECs from patients can be used to generate new hypotheses about mechanisms of human vascular disease.
This work was supported by grants HL131977 (to Dr. Beckman) and the Vanderbilt-Ingram Cancer Center Young Ambassador Award (to Dr. Brown). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Basic to Translational Science author instructions page.
- Received November 7, 2018.
- Revision received May 23, 2019.
- Accepted May 23, 2019.
- 2019 The Authors