LINC00346 regulates NLRP1-mediated pyroptosis and autophagy via binding to microRNA-637 in vascular endothelium injury.

Endothelial injury and dysfunction contributes to atherosclerosis. LINC00346 plays a key role in vascular endothelial cell injury, however, the specific mechanism remains unclear. This study intends to further explore the relationship between LINC00346 and vascular endothelial injury. Circulating LINC00346 was significantly elevated in patients with coronary artery disease and had high diagnostic value for coronary artery disease. In cell experiments, we found that LINC00346 expression was significantly increased in the oxidized low-density lipoprotein (ox-LDL) intervention group, and LINC00346 knockdown delayed ox-LDL induced human umbilical vein endothelial cell (HUVEC) endothelial-to-mesenchymal transition. In addition, knockdown of LINC00346 mitigated ox-LDL-induced NOD-like receptor protein 1 (NLRP1)-mediated inflammasome formation and pyroptosis, but had no significant effect on NLRP3. By observing the number of autophagosome and detecting intracellular autophagic flux, we found that LINC00346 knockdown inhibited the ox-LDL-induced increase in intracellular autophagy level. Dual-luciferase reporter assay, RNA immunoprecipitation assay, and RNA-pull down assay were performed to confirm the inter-molecular interaction. LINC00346 acted as microRNA-637 sponge to up-regulate the expression of NLRP1. Up-regulation of microRNA-637 alleviated NLRP1-mediated pyroptosis in HUVEC and reduced intracellular autophagosome and autolysosome formation. Finally, we explored whether pyropotosis and autophagy interact with each other. We found that inhibition of intracellular autophagy could alleviate NLRP1-mediated pyroptosis. In conclusion, LINC00346 inhibited the activation of NLRP1-mediated pyroptosis and autophagy via binding to microRNA-637, therefore mitigating vascular endothelial injury.

The relationship between elevated serum uric acid and arterial stiffness in a healthy population.

OBJECTIVE: This study aims to investigate the relationship between serum uric acid and arterial stiffness in a healthy population. METHODS: Among the 979 participants, baPWV was non-invasively measured, the circulating levels of uric acid were tested, and the uric acid polymorphisms (rs2231142 and rs11722228) were genotyped. Then, the Mendelian randomization method was employed to test the relationship between serum uric acid and arterial stiffness in a healthy population. RESULTS: After adjusting for age, gender, antihypertensive medication, body mass index, waist-to-hip ratio, urea nitrogen, creatinine and diabetic mellitus, there was a significant allelic difference in uric acid levels for each genotype (P < 0.0001 for rs2231142; P = 0.007 for rs11722228). However, there were no differences on the potential confounders between the genotypes of rs2231142 and rs11722228 (P > 0.05). The baPWV was significantly associated with circulating levels of uric acid after adjusting for cardiovascular risk factors and other potential confounders (P = 0.002). However, neither the single polymorphism, nor the accumulation of culprit alleles was associated with baPWV (P = 0.92 for rs2231142; P = 0.60 for rs11722228; P for trend = 0.77 for the combined analysis of culprit alleles). CONCLUSION: These results do not support the causal role of circulating levels of uric acid in the development of arterial stiffness.

Genetically Elevated Serum Uric Acid and Renal Function in an Apparently Healthy Population.

BACKGROUND: The association between uric acid and kidney disease has been extensively investigated. Numerous studies have reported the association between circulating levels of uric acid and renal function. OBJECTIVES: To test, by the Mendelian randomization method, whether there is a causal association between circulating levels of uric acid and renal function. METHODS: In 989 participants, estimated glomerular filtration rate (eGFR) was calculated, the circulating level of uric acid was tested, and the uric acid polymorphism (rs11722228) was genotyped. RESULTS: After adjusting for age, gender, smoking history, alcohol intake, antihypertensive medication, body mass index, waist-to-hip ratio, and levels of urea nitrogen and creatinine, a significant allelic difference was found in uric acid levels for each genotype (p < 0.0001). Furthermore, the circulating levels of uric acid were negatively associated with eGFR after adjusting for cardiovascular risk factors and other potential confounders (p < 0.0001). Meanwhile, eGFR was significantly associated with the genotypes of rs11722228 (ß = -0.07; p = 0.02). CONCLUSIONS: Evidence from the Mendelian randomization approach implied a causal relationship between uric acid and renal function in an apparently healthy population.

Diagnostic accuracy of a questionnaire and simple home monitoring device in detecting obstructive sleep apnoea in a Chinese population at high cardiovascular risk.

BACKGROUND AND OBJECTIVE: OSA is a common condition associated with cardiovascular (CV) morbidity. It remains underdiagnosed globally in part due to the limited availability and technical requirements of polysomnography (PSG). The aim of this study was to test the accuracy of two simple methods for diagnosing OSA. METHODS: Consecutive subjects identified from a community register with high CV risk were invited to complete the Berlin Sleep Questionnaire and undergo simultaneous, home, overnight PSG and ApneaLink device oximetry and nasal pressure recordings. The relative accuracies of the Berlin Questionnaire, oximetry and nasal pressure results in diagnosing PSG-defined moderate-severe OSA were assessed. RESULTS: Of 257 eligible high CV risk subjects enrolled, 190 completed sleep studies and 143 subjects' studies were of sufficient quality to include in final analyses. Moderate-severe OSA was confirmed in 43% of subjects. The Berlin Questionnaire had low overall diagnostic accuracy in this population. However, ApneaLink recordings of oximetry and nasal pressure areas had high diagnostic utility with areas under the receiver operating characteristic curves of 0.933 and 0.933, respectively. At optimal diagnostic thresholds, oximetry and nasal pressure measurements had similar sensitivity (84% vs 86%) and specificity (84% vs 85%). Technical failure was lower for oximetry than nasal pressure (5.8% vs 18.9% of tests). CONCLUSIONS: In patients with high CV risk overnight single-channel oximetry and nasal pressure measurements may provide high diagnostic accuracy and offer an accessible alternative to full PSG.

Left ventricular hypertrophy in relation to systolic blood pressure and the angiotensin converting enzyme I/D polymorphism in Chinese / 老年心脏病学杂志（英文版）

Objective There is little population-based data on the prevalence and the environmental or genetic determinants of left ventricular hypertrophy (LVH) in China. The purpose of this paper is to study LVH in relation to systolic blood pressure and the angiotensin converting enzyme (ACE) insertion/deletion(I/D) polymorphism in Chinese. Methods We recorded 12-lead ECG (CardioSoft, v4.2) in 1365 residents in the Jingning County, Zhejiang Province, China. LVH was defined according to the gender-specific Sokolow-Lyon and Comell product ECG criteria. Results Regardless of whether the Sokolow-Lyon or Comell product ECG criteria was used, the prevalence of LVH (20.7% and 4.8%, respectively) significantly (P<0.0001) increased with male gender (odds ratio [OR] 2.33 and 7.15) and systolic blood pressure (per 10 mm Hg increase, OR 1.46 and 1.33). If the Sokolow-Lyon criteria was used, the prevalence of LVH was also influenced by alcohol intake (OR 1.44, P=0.03) and body mass index (OR 0.83, P=0.0005). The association between the Sokolow-Lyon voltage amplitude and the ACE I/D polymorphism was dependent on antihypertensive therapy (P=0.01). In 1262 untreated subjects, but not 103 patients on antihypertensive medication, the ACE DD compared with Ⅱ subjects had significantly higher Sokolow-Lyon voltage amplitudes (29.8±0.6 vs. 28.0±20.5 mV, P=0.02) and higher risk of LVH (OR 1.74, 95% CI: 1. 12-2.69, P=0.01). Conclusion LVH is prevalent in Chinese, and is associated with systolic blood pressure and the ACE D allele. The genetic association might be modulated by antihypertensive therapy.

Elasticity indices of large and small arteries in relation to the metabolic syndrome in Chinese.

BACKGROUND: The purpose of this study was to investigate the elasticity of large and small arteries in relation to the components of the metabolic syndrome in a Chinese population. METHODS: Arterial elasticity indices were derived from pulse wave analysis based on a modified Windkessel model in 688 subjects, aged 33-65 years, who volunteered to participate in our study. RESULTS: The study population included 420 (61.0%) men and 433 (62.9%) hypertensive patients, of whom 197 (28.6%) took antihypertensive medication. Overall, the presence of the metabolic syndrome was 20.5%. In univariate analysis, both large artery elasticity index (C1) and small artery elasticity index (C2) were higher in men than in women (P < or = 0.008) and were inversely (P < or = 0.05) correlated with age, systolic and diastolic blood pressure (BP), pulse pressure, pulse rate, and plasma glucose concentration, and positively (P < 0.0001) correlated with body height and body weight. In men, smokers, compared with nonsmokers, had significantly lower C2 (P = 0.007), but they had similar C1 (P = 0.33). In adjusted analysis, patients with the metabolic syndrome, compared with those without, had significantly (P < 0.01) lower C1 and C2. In continuous adjusted analysis, both C1 and C2 were significantly (P < 0.0001) associated with systolic and diastolic BP, whereas in addition, C1 was also significantly associated with plasma glucose concentration (P = 0.007), and C2 with serum high-density lipoprotein (HDL) cholesterol (P = 0.02). CONCLUSIONS: The metabolic syndrome is indeed a risk factor for reduced arterial elasticity.