Downregulation of NUP93 aggravates hypoxia-induced death of cardiomyocytes in vitro through abnormal regulation of gene transcription.

Nuclear pore complex in the nuclear envelope plays an important role in controlling the transportation of RNAs, proteins and other macromolecules between the nucleus and cytoplasm. The relationship between abnormal expression of nucleoporins and cardiovascular diseases is unclear. In this study we investigated how myocardial infarction affected the expression and function of nucleoporins in cardiomyocytes. We separately knocked down 27 nucleoporins in rat primary myocardial cells. Among 27 nucleoporins, knockdown of Nup93, Nup210 and Nup214 markedly increased the expression of ANP and BNP, two molecular markers of cardiomyocyte function. We showed that Nup93 was significantly downregulated in hypoxic cardiomyocytes. Knockdown of Nup93 aggravated hypoxia-induced injury and cell death of cardiomyocytes, whereas overexpression of Nup93 led to the opposite effects. RNA-seq and bioinformatics analysis revealed that knockdown of Nup93 did not affect the overall transportation of mRNAs from the nucleus to the cytoplasm, but regulated the transcription of a large number of mRNAs in cardiomyocytes, which are mainly involved in oxidative phosphorylation and ribosome subunits. Most of the down-regulated genes by Nup93 knockdown overlapped with the genes whose promoters could be directly bound by Nup93. Among these genes, we demonstrated that Nup93 knockdown significantly down-regulated the expression of YAP1. Overexpression of YAP1 partially rescued the function of Nup93 knockdown and attenuated the effects of hypoxia on cell injury and cardiomyocyte death. We conclude that down-regulation of Nup93, at least partially, contributes to hypoxia-induced injury and cardiomyocyte death through abnormal interaction with the genome to dynamically regulate the transcription of YAP1 and other genes. These results reveal a new mechanism of Nup93 and might provide new therapeutic targets for the treatment of ischemia-induced heart failure.

Association between cardiovascular risk factors and stage 1 hypertension defined by the 2017 ACC/AHA guidelines.

BACKGROUND: A blood pressure (BP) of 130-139/80-89 mmHg has been defined as stage 1 hypertension by the 2017 American College of Cardiology/American Heart Association High Blood Pressure Clinical Practice Guidelines. This study was conducted to assess the association of cardiovascular risk factors (CRFs) and newly defined stage 1 hypertension in China. METHODS: We analyzed the data of 84,489 adults with a BP of <140/90 mmHg. The 10-year cardiovascular disease (CVD) risk score was calculated using the China-PAR equation. Logistic analysis was used to assess the association between CRFs and stage 1 hypertension. RESULTS: The mean values of CRFs, the proportion of metabolic abnormalities, the prevalence of ≥2 CRFs, and the 10-year CVD risk of individuals with a BP of 130-139/80-89 mmHg were significantly higher than those of the population with a BP of <130/80 mmHg. The adjusted odds ratios (ORs) of waist circumference, fasting plasma glucose (FPG), and triglycerides were 1.362 (CI 95% = 1.081-1.715, p = .009), 1.264 (CI 95% = 1.093-1.462, p = .002), and 1.331 (CI 95% = 1.009-1.755, p = .043), respectively. Other CRFs were not significantly associated with stage 1 hypertension. CONCLUSIONS: Multidisciplinary and targeted interventions are required to manage the CRFs (especially abdominal obesity, elevated FPG, and hypertriglyceridemia) of the population with a BP of 130-139/80-89 mmHg in China.

High level of circulating microRNA-142 is associated with acute myocardial infarction and reduced survival.

BACKGROUND: Recent study reported that microRNA-142 (miR-142) were up-regulated in the atherosclerotic plaques, which may be responsible for pathogenesis of atherosclerosis. However, whether it associates with presence of acute myocardial infarction (AMI), and its prognostic value is still unknown. We, therefore, investigated the association between miR-142 expression and presence of AMI, and its prognostic value in AMI patients. METHODS: We included 300 AMI patients and 100 subjects as the control group. MiR-142 content was detected by quantitative real-time polymerase chain reaction. MiR-142 level was identified in all subjects. The multivariate logistic regression analysis were performed to evaluate the risk factors of AMI. The Kaplan-Meier analysis was performed to determine the major adverse cardiovascular and cerebrovascular events (MACCE)-free survival. RESULTS: AMI group had significantly higher miR-142 level in comparison to the controls [4.10 (2.03-7.43) vs. 1.92 (0.91-2.91), p < 0.001], moreover, miR-142 content was significantly associated with cardiac troponin I (cTnI) level (r = 0.707, p < 0.001). The MACCE-free survival was significantly lower over 24-month for patients in miR-142 high expression group (72.4% ± 5.6% vs. 76.4% ± 5.1%) (p = 0.022). After adjusting for the traditional risk factors, the odds ratios of miR-142 was 14.74 (95% CI, 2.15-101.24). The multivariate logistic regression analysis revealed that miR-142 level significantly associated with presence of AMI (p < 0.001). CONCLUSION: The serum level of miR-142 was increased in AMI patients when compared with health population. Furthermore, use of this marker may allow a certain predictor of the MACCE in AMI patients.