Pulmonary arterial hypertension (PAH) is characterized by pulmonary vascular remodeling of the precapillary pulmonary arteries, with excessive proliferation of vascular cells. This study was performed to examine the effects of long noncoding RNA CPS1 intronic transcript 1 (CPS1-IT) on PAH in rat models of obstructive sleep apnea (OSA) through regulating interleukin (IL)-1β expression. The OSA models were induced in rats, for determination of the CPS1-IT expression. The binding of CPS1-IT and hypoxia-inducible factor 1 (HIF1) was verified. To analyze the effects of CPS1-IT on PAH, the overexpression vector of CPS1-IT and HIF1, shRNA against IL-1β and pyrrolidine dithiocarbamate (PDTC, inhibitor of the NF-κB signaling pathway) were injected into rat models, respectively. The blood pressure and activity of biochemical indicators including nitric oxide (NO), nitric oxide synthase (NOS), superoxide dismutase (SOD), and lipid peroxide (LPO) were assessed. The expression of IL-1β, HIF1, α-smooth muscle actin (α-SMA), proliferating cell nuclear antigen (PCNA), and fibronectin (FN) was determined. The relationship of CPS1-IT to IL-1β and NF-κB was evaluated. CPS1-IT was downregulated in the OSA rat model. Overexpressed CPS1-IT increased the activity of NO, NOS, and SOD as well as α-SMA expression, whereas decreasing LPO activity and expression of PCNA and FN, whereby PAH was suppressed. Notably, overexpressed CPS1-IT reduced IL-1β expression through NF-κB signaling pathway via inhibiting the HIF1 transcriptional activity, suggesting a mechanism affecting PAH. To conclude, overexpressed CPS1-IT alleviated PAH in OSA by reducing IL-1β expression, the mechanism of which was involved with inhibited HIF1 transcriptional activity and the NF-κB signaling pathway. K E Y W O R D S hypoxia-inducible factor 1, interleukin-1β, long noncoding RNA CPS1 intronic transcript 1, nuclear factor-κB, obstructive sleep apnea, pulmonary arterial hypertension, transcriptional activity Overexpressed long noncoding RNA CPS1-IT alleviates pulmonary arterial hypertension in obstructive sleep apnea by reducing interleukin-1β expression via HIF1 transcriptional activity.

Inhaled nitric oxide can lead to a decrease in levels of cardiac troponin I, von Willebrand factor, glycoprotein, and granule membrane protein 140, after an established myocardial damage, provoked by acute massive pulmonary embolism.

Background Obstructive sleep apnea (OSA) increases health risks of cardiovascular disease and stroke. Both genetic factors and environmental exposures contribute to the occurrence of OSA. The purpose of this study was to determine the role of four functional inflammatory single nucleotide polymorphisms (SNPs) (VWF rs1063856, IL‐6 rs1800796, TNF rs1800629, and CRP rs2794521) in the susceptibility and severity of OSA. Methods A case–control study of OSA among Chinese population was conducted. Genotyping was performed using ABI TaqMan SNP genotyping technique. Results We found VWF rs1063856 (OR = 1.50, 95% CIs = 1.10–2.04; p = 0.010), IL‐6 rs1800796 (OR = 1.32, 95% CIs = 1.11–1.56; p = 0.002), TNF rs1800629 (OR = 1.44, 95% CIs = 1.13–1.83; p = 0.003), and CRP rs2794521 (OR = 1.27, 95% CIs = 1.04–1.55; p = 0.021) were all significantly associated with increased susceptibility of OSA, while VWF rs1063856 (OR = 1.75, 95% CIs = 1.18–2.62; p = 0.006), IL‐6 rs1800796 (OR = 1.39, 95% CIs = 1.10–1.76; p = 0.006) were associated with the severity of OSA. Conclusions Our study indicated that functional variants of inflammatory biomarkers could cause the occurrence of OSA and influence the severity of OSA. These findings further support that inflammatory cytokines were closely related to the occurrence and development of OSA.

The aim of the present study was to investigate the effect of nitric oxide inhalation (NOI) on cardiac troponin I (CTnI) levels and mean pulmonary arterial pressure (mPAP) in rabbits with acute massive pulmonary embolism (AMPE). Thirty rabbits were used as animal models for AMPE and received different treatments. A total of 4 h after successful modeling, the control group (CON, n=10) received conventional thrombolysis, whereas the treatment group (TRE, n=10) received conventional thrombolysis plus NOI. The experimental group (EXP, n=10) did not receive any treatments. Myocardial necrosis was pathologically confirmed in all 30 rabbits. In group EXP, the post-AMPE CTnI peak level was 0.42±0.12 µg/l, was achieved in 18.8±4.5 h and remained positive for 38.6±5.2 h (≥0.1 µg/l). These values were lower in group TRE when compared with those in groups CON and EXP (P<0.05). Group TRE exhibited significantly reduced mPAP at 24, 28, 32, and 34 h (P<0.05) when compared with group CON. AMPE-induced cardiac impairment was more severe in group EXP when compared with groups CON and TRE. The present findings indicated that the CTnI peak was significantly correlated with the corresponding mPAP. Furthermore, the results suggested NOI may reduce mPAP and CTnI peak levels, with protective effects against AMPE-induced myocardial damage in rabbits.

Increases in plasma TXA2, PGI2 and ET-1 levels causes myocardial damage in a rabbit model of AMPE; however, NOI effectively down regulates the plasma concentration of these molecules to produce a myocardial-protective effect.