3,4-dihydroxyacetophenone inhibits hypoxia-associated human pulmonary artery smooth muscle cell proliferation by reducing Ca2+ influx.

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 hypoxia-induced 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.

• Authors: Chunlong Lin, Caixia Li, Jianping Zhao, Wang Ni, Jizu Yi
• Journal: Pakistan journal of pharmaceutical sciences (Pak J Pharm Sci) Vol. 34 Issue 1 Pg. 157-163 (Jan 2021) ISSN: 1011-601X [Print] Pakistan
• PMID: 34248015 (Publication Type: Journal Article)

Chemical References

• Acetophenones
• 3,4-dihydroxyacetophenone
• Calcium

Topics

• Acetophenones (pharmacology)
• Adult
• Calcium (metabolism)
• Cell Hypoxia (drug effects, physiology)
• Cell Proliferation (drug effects, physiology)
• Cells, Cultured
• Female
• Humans
• Male
• Middle Aged
• Muscle, Smooth, Vascular (drug effects, metabolism)
• Myocytes, Smooth Muscle (drug effects, metabolism)
• Pulmonary Artery (cytology, drug effects, metabolism)