[The Association Between Bone Morphogenic Protein-4 and in-situ Saphenous Vein Graft Pathology in Diabetic Patients
Hong-Wei Zhang1, Jun Gu1, Er-Yong Zhang1
1Department of Cardiovascular Surgery, West China Hospital, Sichuan University,Chengdu 610041,China.
Objectives:
This study was designed to assess the expression levels of bone morphogenic protein-4 (BMP4) in saphenous veins harvested from diabetic patients undergoing coronary artery bypass grafting (CABG), and to investigate its association with in-situ morphological and pathological changes within the venous wall.
Methods:
From January 2013 to December 2014, forty patients with type 2 diabetes mellitus (DM) and risk factors matched non-DM controls (n =40) were enrolled prospectively. Of the 40 DM patients, 24 had noninsulin-dependent diabetes (NIDM) and the remaining 16 had insulin-dependent diabetes (IDM). Segments of saphenous vein without surgical dilatation from these 80 patients were obtained. Vessel wall characteristics were evaluated by hematoxylin-eosin (HE) staining, and the expression and distribution of BMP4 was assessed by Western blot assay and immunohistochemistry analysis.
Results:
The intimal and medial thickness of the saphenous veins harvested from DM patients were higher than those from non-DM controls. Compared with non-DM patients, the expression level of BMP4 was significantly elevated in diabetic veins ( P<0.05), and BMP4 was highly expressed in smooth muscle cells located in the medial layer. Moreover, the expression levels of BMP4 in diabetic veins were significantly correlated with intimal thickness (r =0.655, P<0.01), intimal area (r =0.684, P<0.01), medial thickness (r =0.642, P<0.01) and medial area (r =0.692, P<0.01).
Conclusions:
The pre-existing intimal and medial hyperplasia were significantly correlated with the high expression levels of BMP4 in saphenous veins harvested from diabetic patients, implying a potential role of BMP4 in the progression of vein graft stenotic diseases in this cohort of post-CABG patients. Future studies were warranted in investigating novel therapeutic strategy targeting at BMP4 for improving long-term vein graft patency.
