3,4-dihydroxyacetophenone inhibits hypoxia-associated human 2+ pulmonary artery smooth muscle cell proliferation by reducing Ca influx | Pakistan Journal of Pharmaceutical Sciences 2021

Author(s)

Chunlong Lin Department of Chemistry and Chemical Engineering, Hunan Institute of Science and Technology,Yueyang, Hunan,China

Caixia Li Department of Chemistry and Chemical Engineering, Hunan Institute of Science and Technology,Yueyang, Hunan,China

Jianping Zhao Department of Chemistry and Chemical Engineering, Hunan Institute of Science and Technology,Yueyang, Hunan,China

Wang Ni Department of Chemistry and Chemical Engineering, Hunan Institute of Science and Technology,Yueyang, Hunan,China

Jizu Yi Department of Chemistry and Chemical Engineering, Hunan Institute of Science and Technology,Yueyang, Hunan,China

Abstract

The present study aimed to assess the effects of 3,4-dihydroxyacetophenone (DHAP) on human pulmonary artery smooth muscle cells (HPASMCs). HPASMCs were divided into the normoxia group (NG), hypoxia group (HG), and hypoxia and 0.6×10-4 mol/L (HD1), 1.9×10-4 mol/L (HD2) and 6.0×10-4 mol/L (HD3) DHAP treatment groups. Cell cycle was analyzed by flow-cytometrically. HPASMC growth was examined by the proliferating cell nuclear antigen (PCNA) and MTT assays. Intracellular Ca2+ ([Ca2+]i) was measured by laser scanning confocal microscopy. Compared with the NG, the HG showed significantly increased HPASMC proliferation (P<0.05); meanwhile, cells treated with DHAP showed decreased proliferation compared with the HG (P<0.05). Hypoxia enhanced cell cycle progression and DHAP partly restored cell cycle distribution toward the status of NG cells. Furthermore, CDK2 levels were markedly increased in hypoxic cells (P<0.05), while DHAP treatment starkly decreased CDK2 levels in comparison with the HG (P<0.05). Moreover, hypoxia increased intracellular [Ca2+] levels compared with normoxia (P<0.05); meanwhile, DHAP treatment decreased [Ca2+]i compared with the HG (P<0.05). These findings suggested that DHAP inhibits hypoxiainduced proliferation of HPASMCs involving [Ca2+]i reduction. Therefore, DHAP should be considered an ideal candidate for the prevention and/or treatment of hypoxia-associated pulmonary hypertension and pulmonary vascular remodeling.

Publication Details

Page(s) 157-163

DOI DOI not available

Published Journal: Pakistan Journal of Pharmaceutical Sciences, Volume: 34, Issue: 1, Year: 2021

Keywords

Hypoxia Hypoxia pulmonary hypertension pulmonary artery smooth muscle cell cell cycle pulmonary vascular remodeling 4dihydroxyacetophenone

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