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.
