ORIGINAL PAPER 15-HETE suppresses K + channel activity and inhibits apoptosis in pulmonary artery smooth muscle cells Yumei Li Æ Qian Li Æ Zhigang Wang Æ Di Liang Æ Shujun Liang Æ Xiaobo Tang Æ Lei Guo Æ Rong Zhang Æ Daling Zhu Published online: 10 December 2008 Ó Springer Science+Business Media, LLC 2008 Abstract 15-Hydroxyeicosatetraenoic acid (15-HETE) is an important hypoxic product from arachidonic acid (AA) in the wall of pulmonary vessels. Although its effects on pulmonary artery constriction are well known, it remains unclear whether 15-HETE acts on the apoptotic responses in pulmonary artery smooth muscle cells (PASMCs) and whether K ? channels participate in this process. These hypothesises were validated by cell viability assay, termi- nal deoxynucleotidyl transferase-mediated dUTP nick end- labeling, mitochondrial potentials assay, caspase activity assay and western blot. We found that 15-HETE enhanced cell survival, suppressed the expression and activity of caspase-3, upregulated bcl-2 and attenuated mitochondrial depolarization, prevented chromatin condensation and partly reversed K ? channel opener-induced apoptosis in PASMCs under serum-deprived conditions. Our data indicated that 15-HETE inhibits the apoptosis in PASMCs through, at least in part, inactivating K ? channels. Keywords 15-Hydroxyeicosatetraenoic acid Á Pulmonary artery muscle smooth cells Á Hypoxia-induced pulmonary hypertension Á Apoptosis Á K ? channel Abbreviations 15-HETE 15-Hydroxyeicosatetraenoic acid PASMCs Pulmonary artery smooth muscle cells AA Arachidonic acid 15-LO 15-Lipoxygenase HPV Hypoxic pulmonary vasoconstriction PVR Pulmonary vascular remodeling NDGA Nordihydroguaiaretic acid Introduction Chronic hypoxic exposure induces many pathophysiologi- cal changes, such as sustained pulmonary vasoconstriction, pulmonary arteries medial muscularization, artherosclerosis and diffuse interstitial fibrosis [1–3]. Chronic hypoxia is also an important contributor to the pulmonary vascular remodeling (characterized with medial and intimal hyper- trophy), a critical pathological alteration in pulmonary hypertension. However, the mechanism of pulmonary vas- cular remodeling (PVR) and pulmonary hypertension is still unknown. Some investigators suggested that PASMC pro- liferation was the main reason for the vascular remodeling in lung [4]. But some studies reported that hypoxia-induced proliferation of medial PASMCs was not observed, instead of the inhibition of apoptotic responses in SMC [5, 6]. Therefore, it’s believable that the disturbance between apoptosis and proliferation in PASMC under hypoxic con- ditions plays an important role in the progression of PVR. Compared with a large amount of reports on hypoxia- induced proliferation in pulmonary vasculature [7–9], the effects of chronic exposure on the apoptotic responses in PASMCs still need to be determined. Yumei Li and Qian Li contributed equally to this work. Y. Li Á Q. Li Á Z. Wang Á D. Liang Á S. Liang Á X. Tang Á L. Guo Á R. Zhang Á D. Zhu (&) Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University, 157 Baojian Road, Nangang District, Harbin 150081, Heilongjiang, People’s Republic of China e-mail: dalingz@yahoo.com X. Tang Á D. Zhu Bio-Pharmaceutical Key Laboratory of Heilongjiang Province, Harbin 150081, People’s Republic of China 123 Apoptosis (2009) 14:42–51 DOI 10.1007/s10495-008-0286-6