Triptolide inhibits PDGF-induced proliferation of ASMCs through G0/G1 cell cycle arrest and suppression of the AKT/NF-κB/cyclinD1 signaling pathway.

Abnormal proliferation of airway smooth muscle cells (ASMCs) is a hallmark of airway remodeling. Platelet-derived growth factor (PDGF) is known to be a major stimulus inducing the proliferation of ASMCs. It has been reported that triptolide demonstrates protective effects against airway remodeling. In this study, we investigated the antiproliferative effects of triptolide on PDGF-induced ASMCs and its underlying mechanisms. Cell proliferation was determined using the Cell Counting Kit-8 (CCK-8) assay. Flow cytometry was used to study the influence of triptolide on cell cycle and apoptosis. Quantitative real-time PCR and Western blot analysis were employed to detect the expression of proliferating cell nuclear antigen (PCNA), cyclinD1 and cyclin dependent kinase 4 (CDK4). Proteins involved in the protein kinase B (AKT) and nuclear factor kappa B (NF-κB) signaling pathways were evaluated using Western blot analysis. Triptolide could significantly inhibit cell proliferation, induce cell cycle arrest in the G0/G1 phase, and reduce the expression of PCNA, cyclinD1, and CDK4 in PDGF-treated ASMCs. Levels of phosphorylated AKT, p65 and NF-κB inhibitor α (IκBα) stimulated by the presence of PDGF were markedly suppressed after triptolide treatment. Moreover, triptolide cotreatment with the phosphatidylinositol 3 kinase (PI3k) inhibitor, 2-(4-morpholinyl)-8-phenylchromone (LY294002), could further suppress the proliferation, NF-κB activation and cyclinD1 expression. Similar results were observed after triptolide cotreatment with the NF-κB inhibitor, ammonium pyrrolidinedithiocarbamate (PDTC). Our results suggest that triptolide could inhibit the PDGF-induced proliferation of ASMCs through G0/G1 cell cycle arrest and suppression of the AKT/NF-κB/cyclinD1 signaling pathway.

Prevalence, Awareness, and Treatment of Isolated Diastolic Hypertension: Insights From the China PEACE Million Persons Project.

Background Characterizing and assessing the prevalence, awareness, and treatment patterns of patients with isolated diastolic hypertension (IDH) can generate new knowledge and highlight opportunities to improve their care. Methods and Results We used data from the China PEACE (Patient-centered Evaluative Assessment of Cardiac Events) Million Persons Project, which screened 2 351 035 participants aged 35 to 75 years between 2014 and 2018. IDH was defined as systolic and diastolic blood pressure of <140 and ≥90 mm Hg; awareness as self-reported diagnosis of hypertension; and treatment as current use of antihypertensive medications. Of the 2 310 184 participants included (mean age 55.7 years; 59.5% women); 73 279 (3.2%) had IDH, of whom 63 112 (86.1%) were untreated, and only 6512 (10.3%) of the untreated were aware of having hypertension. When compared with normotensives, participants who were <60 years, men, at least college educated, had body mass index of >28 kg/m2, consumed alcohol, had diabetes mellitus, and prior cardiovascular events were more likely to have IDH (all P<0.01). Among those with IDH, higher likelihood of awareness was associated with increased age, women, college education, body mass index of >28 kg/m2, higher income, diabetes mellitus, prior cardiovascular events, and Central or Eastern region (all P<0.05). Most treated participants with IDH reported taking only 1 class of antihypertensive medication. Conclusions IDH affects a substantial number of people in China, however, few are aware of having hypertension and most treated participants are poorly managed, which suggests the need to improve the diagnosis and treatment of people with IDH.