Endothelial progenitor cells, rosuvastatin and valsartan have a comparable effect on repair of balloon-denudated carotid artery injury

Jiunn-Jye Sheu; Hao-Yi Hsiao; Sheng-Ying Chung; Sarah Chua; Kuan-Hung Chen; Pei-Hsun Sung; Fan-Yen Lee; Hung-I Lu; Yi-Ling Chen; Yi-Chen Li; Hsueh-Wen Chang; Sheung-Fat Ko; Hon-Kan Yip

Endothelial progenitor cells, rosuvastatin and valsartan have a comparable effect on repair of balloon-denudated carotid artery injury

Am J Transl Res. 2019 Mar 15;11(3):1282-1298. eCollection 2019.

Authors

Jiunn-Jye Sheu^{1

2

3}, Hao-Yi Hsiao⁴, Sheng-Ying Chung⁴, Sarah Chua⁴, Kuan-Hung Chen⁵, Pei-Hsun Sung^{4

3}, Fan-Yen Lee^{1

6

2

3}, Hung-I Lu¹, Yi-Ling Chen^{4

2}, Yi-Chen Li⁴, Hsueh-Wen Chang⁷, Sheung-Fat Ko⁸, Hon-Kan Yip^{4

2

3

9

10}

Affiliations

¹ Division of Thoracic and Cardiovascular Surgery, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung 83301, Taiwan.
² Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital Kaohsiung, Taiwan.
³ Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital Kaohsiung, Taiwan.
⁴ Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung 83301, Taiwan.
⁵ Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung 83301, Taiwan.
⁶ Division of Cardiovascular Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center Taiwan.
⁷ Department of Biological Sciences, National Sun Yat-Sen University Kaohsiung 80424, Taiwan.
⁸ Department of Radiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung 83301, Taiwan.
⁹ Department of Medical Research, China Medical University Hospital, China Medical University Taichung 40402, Taiwan.
¹⁰ Department of Nursing, Asia University Taichung 41354, Taiwan.

PMID: 30972162
PMCID: PMC6456547

Abstract

Endothelial cell (EC) dysfunction plays a crucial role for arterial obstructive disease. This study tested the therapeutic role of autologous endothelial progenitor cells (EPCs)/rosuvastatin-(Rosu)/valsartan-(Val) on repair of injured carotid ECs. Male Sprague-Dawley rats (n = 60) were categorized into five groups [sham-control (SC), left common carotid artery injury induced by balloon denudation (LCA^BD), LCA^BD + Rosu (10 mg/kg/day), LCA^BD + Val (20 mg/kg/day), and LCA^BD + EPC (1.2 × 10⁶)]. By day 5, the LCA was harvested from each rat (n = 6/each time interval in group) after the procedure. Carotid-ring angiogenesis was significantly lower in LCA^BD than the other groups (all P < 0.001). Compared with LCA^BD, the number of EC was significantly higher in LCA^BD treated with adipose-derived mesenchymal stem cells (ADMSCs) and more significantly higher in LCA^BD treated with EPCs (all P < 0.001). Gene expression of EC (CD31/vWF), EPC (SDF-1α/CXCR4) and angiogenesis (VEGF/VEGF-receptor/angiopoietin/eNOS) and EC intercellular junction (VE-cadherin) biomarkers were significantly lower in LCA^BD than in groups LCA^BD + Rosu to LCA^BD + EPC (all P < 0.001). Conversely, the gene expression of inflammatory (VCAM-1/MMP-9/TNF-α), oxidative-stress (NOX-1/NOX-2), apoptosis (cleaved caspase-3/PARP) and thrombin cofactor (thrombomodulin) biomarkers were significantly higher in LCA^BD than in other groups (all P < 0.001). By day 14, the neointimal-layer area and cellular expressions of (CD40+/CD68+) were highest in LCA^BD, lowest in SC, significantly higher in LCA^BD + Val than in LCA^BD + Rosu and LCA^BD + EPC (all P < 0.001). In conclusion, EPCs were comparable to rosuvastatin and valsartan in upregulation of angiogenesis and repair of injured carotid ECs.

Keywords: Balloon denudation; angiogenesis; carotid artery; endothelial cell damage; inflammation.