Expression of aromatase following angiotensin II stimulation in coronary vascular smooth muscle cells and cardiac fibroblasts

Abstract

Aromatase converts testosterone to estrogen and is a key regulator of the balance between androgens and estrogens. Since sex steroids have been implicated in the outcome of cardiovascular disease, we investigated whether aromatase or androgen receptor (AR) expression was modified in human coronary vascular smooth muscle cells (HCVSM) and rat cardiac fibroblasts (RCF) following stimulation with a pathological mediator of heart disease (angiotensin II: AngII). Primary HCVSM (passage 8) and RCF (passage 0) were grown to 80% confluence and treated with AngII (24 hr; 10−7M). Cell type was characterized by expression of DDR2 (fibroblast) and α‐smooth muscle actin (HCVSM). We demonstrate that AngII increased expression of both aromatase (76%, p<0.05) and androgen receptor (AR: 65%, p<0.05) in HCVSM. In cardiac fibroblasts AngII produced a trend toward increased aromatase expression (23%, p=0.08) and although AR expression was not altered by AngII we are the first to report the presence of AR expression in cardiac fibroblasts. In conclusion, the presence of aromatase and AR in these two cell types suggests a possibility for circulating testosterone to act locally in an androgenic and/or estrogenic fashion. However the functional consequence of upregulation of both estrogenic (aromatase) and androgenic (AR) systems in HCVSM following AngII stimulation remains to be determined. Sarver Heart Center (TH) and AHA (RG).