苯芘抑制血管新生之影響:骨型態發生蛋白訊息傳遞角色之探討

Abstract

Benzo[a]pyrene (B[a]P), one of the polycyclic aromatic hydrocarbons family (PAHs), is a common environmental pollutant from cigarette smoke, charbroiled food, industrial combustion products and diesel exhaust. Emerging evidence showed that PAHs cause cardiovascular disease (CVD). Epidemiological studies indicate that smoking is responsible for one third of all CVD deaths, and each cigarette contains 19-50 ng B[a]P. Thus, exposure to B[a]P is associated with high risk CVD. In physiology, angiogenesis is thought to be a defense mechanism which protects tissue from ischemia. However, our previous studies showed that exposure to B[a]P could inhibit angiogenesis and the mechanisms need to be further investigated. Bone morphogenetic proteins (BMPs) belong to the TGF-β superfamily involved in development, differention, cancer and angiogenesis. Abnormal BMP signaling may cause different CVD, therefore our aim is to investigate whether BMP signaling is involved in B[a]P-inhibited angiogenesis. We found that B[a]P could decrease the protein expression of BMP receptor 1A (BMPR1A), Id-1 and the level of Smad1/5 phosphorylation in a dose- and time-dependent manner. Moreover, B[a]P could decrease tube formation in HUVECs. Nevertheless, B[a]P treatment did not alter the mRNA expression of BMPR1A which indicated that B[a]P inhibited BMP signaling may be through post-translational modifications. By employing aryl hydrocarbon receptor (AhR) antagonist,