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Home > Medical Professionals > Research Initiatives Conference > Poster Abstracts Accepted > Bafford Mineralocorticoid Receptor

Mineralocorticoid Receptor (MR) Expression in Vein Grafts: A Potential Role for Aldosterone in Vein Graft Disease

Richard Bafford¹, Xin Xin Sui¹, Min J Park¹, Jose R Romero², Gail K Adler², Gordon H Williams², Raouf A Khalil¹, Michael S Conte^1
1Brigham and Women's Hospital, Vascular Surgery Research Laboratory, Boston, MA;²Brigham and Women's Hospital, Division of Endocrinology, Diabetes, and Hypertension, Boston, MA

Objectives: Experimental studies have suggested an important role for the local renin-angiotensin system (RAS) in vein graft disease, though clinical evidence is lacking. Recent evidence has suggested that the mineralocorticoid aldosterone (ALDO), via activation of the MR, is an important amplifier of RAS-activation and potential mediator of vascular damage. ALDO/MR signaling has been associated with inflammation, fibrosis, and hypertrophic changes in target tissues, including the heart. We hypothesize that MR activation contributes to the injury response in vein bypass grafts.
Methods: Specimens of greater saphenous vein (GSV; N=6) and excised lesions of diseased lower extremity vein grafts (HVG; N=15, 84-1330 days post-bypass) were obtained under an IRB approved protocol. NZW rabbits (N= 15) underwent carotid interposition grafts using jugular vein, and vessels were harvested 1-51 days after surgery. Immunostaining was performed on human and rabbit vein sections using a mAb to MR with non-specific IgG controls. RT-PCR was performed using primers specific for MR and 11-β-hydroxysteroid dehydrogenase-2 (11βHSD2 ; a key enzyme which inactivates cortisol and confers ALDO specificity for MR in tissues where they are co-expressed). Gene expression was also examined in primary cultures of human smooth muscle cells (SMC) from GSV, and a control human embryonic kidney cell line (293).
Results: By immunostaining, MR expression was observed in all HVG lesions examined, with none or minimal staining in normal GSV. MR expression in diseased HVG appeared transmural, but was strongest in the media and adventitia. Similar findings were obtained in rabbit vein grafts, particularly in those 14 days of age or older. RT-PCR revealed upregulated expression of both MR and 11βHSD2 in rabbit vein grafts, beginning at approximately 1 week post-bypass and increasing through 51 days (figure 1). The identity of the PCR products obtained from rabbit templates was confirmed by DNA sequencing. By RT-PCR, MR and 11βHSD2 expression was seen in cultured 293 and SMC. Normal GSV expressed minimal MR and no detectable 11βHSD2; in contrast diseased HVG demonstrated expression of both genes though variability of magnitude was noted (figure 2).
Conclusions: Co-expression of MR and 11βHSD2 in arterialized veins suggests that the vein graft may constitute a novel target for ALDO-mediated tissue injury. ALDO/MR signaling may have relevance to the pathogenesis of vein graft disease.