Data_Sheet_1_Osteopontin N-Terminal Function in an Abdominal Aortic Aneurysm From Apolipoprotein E-Deficient Mice.pdf

The cleavage of osteopontin (OPN) by thrombin results in an N-terminal fragment (OPN-N), which exposes a cryptic integrin-binding motif that promotes the adherence of cells, and plays a proinflammatory role. However, the effect of OPN-N on abdominal aortic aneurysm (AAA) remains unknown. The aim of this study was to investigate the expression of OPN-N in aortic tissue samples obtained from patients, who underwent acute aortic dissection (AD), and normal aorta, effect of OPN-N on angiotensin (Ang) II-induced AAA in mice, and relationship between OPN-N and pyroptosis-related inflammatory factors in vitro. Hematoxylin and eosin staining was conducted to detect histological changes. Next, we detected the expression of the OPN-N protein. Additionally, ApoE−/− mice were divided into four groups: control, control + M5Ab (to block the OPN-N function in mice), Ang II, and Ang II + M5Ab. All mice were euthanized after a 28-day infusion and whole aortas, including thoracic and abdominal aortas, were collected for morphological and histological analysis of the AAA. The OPN-N protein expression was higher in patients with AD than in normal individuals, while histological changes in the aortas of Ang II mice were suppressed in Ang II + M5Ab mice. The expression of OPN-N, NOD-, LRR-, and pyrin domain-containing protein 3, pro-Caspase-1, ASC, Gasdermin-d, interleukin (IL)-18, IL-1β, matrix metalloproteinase (MMP) 2, and MMP9 was lower in the Ang II + M5Ab group than in the Ang II group. The gene expression of monocyte chemoattractant protein-1, IL-6, and tumor necrosis factor-α was suppressed in the aortic tissues of the Ang II + M5Ab group compared with the Ang II group. Moreover, the expression of α-smooth muscle actin was lower in the Ang II group than in the Ang II + M5Ab group. In vitro results showed that the increase in the expression of pyroptosis-related inflammatory factors induced by OPN was mediated through the nuclear factor (NF)-κB pathway. In conclusion, OPN-N promotes AAA by increasing the expression of pyroptosis-related inflammatory factors through the NF-κB pathway, inflammation, and extracellular matrix degradation. These results highlight the potential of OPN-N as a new therapeutic target to prevent AAA expansion.</p

Table_1_Comparison of saline infusion test and captopril challenge test in the diagnosis of Chinese with primary aldosteronism in different age groups.doc

BackgroundTo explore the diagnostic accuracy and the optimal cutoff value between the saline infusion test (SIT) and captopril challenge test (CCT) [including the value and suppression of plasma aldosterone concentration (PAC)] for primary aldosteronism (PA) diagnosing.MethodsA total of 318 patients with hypertension were consecutively enrolled, including 126 patients with PA and 192 patients with essential hypertension (EH), in this observational study. The characteristics of patients and laboratory examinations were collected and compared. The comparison between SIT and CCT was carried by drawing the receiver operator characteristic curve (ROC) and calculating the area under the curve (AUC) to explore the diagnostic accuracy and the optimal cutoff value.ResultsThe average age was 51.59 ± 10.43 in the PA group and 45.72 ± 12.44 in the EH group (pConclusionCompared with SIT, CCT had a higher diagnostic value when post-CCT PAC was used as the diagnostic criterion in Chinese people, while the selection of diagnostic thresholds depended on patient age.</p

Data_Sheet_1_Assessing the causal role of hypertension on left atrial and left ventricular structure and function: A two-sample Mendelian randomization study.docx

AimThe aim of this study was to investigate whether hypertension may be causally linked to left atrial (LA) and left ventricular (LV) structure and function.Methods and resultsWe performed a two-Mendelian randomization (MR) analysis implementing the results from the FinnGen large-scale, genome-wide association study for hypertension (N = 218,754), and LV (N = 16,923) and LA studies (N = 35,648) by the UK Biobank to identify genetic instruments. The MR analysis was implemented using an inverse-variance weighted (IVW) approach. We identified a positive potential causal relationship between hypertension and indices for the LA maximum (LAmax with causal estimates of 0.126 [95% CI, (0.093 to 0.160)]); LA minimum (LAmin with causal estimates of 0.122 [95% CI, (0.089 to 0.156)]); LV function (causal estimates are LV end-diastolic volume (LVEDV), 0.078 [95% CI, (0.003 to 0.153)]; LV end-systolic volume (LVESV), 0.102 [95% CI, (0.030 to 0.173)]; LV mass (LVM), 0.171 [95% CI, (0.108 to 0.233)]; and LV mass to end-diastolic volume ratio (LVMVR at 0.098 [95% CI, (0.048 to 0.149)], respectively), which was directionally concordant with other robust MR methods. Other than this, we observed a significantly negative causal relationship between hypertension and the LA active emptying fraction (LAAEF), the LA passive emptying fraction (LAPEF), and the LA total emptying fraction (LATEF).ConclusionOur genetic analyses demonstrated a potential causal relationship between hypertension and the left atrium and left ventricle’s structures and functions.</p

Table_1_The association between arterial stiffness and cancer occurrence: Data from Kailuan cohort study.DOCX

BackgroundThis study aimed to investigate whether increased arterial stiffness, measured by brachial-ankle pulse wave velocity (baPWV) is associated with cancer.Materials and methodsA total of 45,627 Chinese adults underwent a baPWV examination. The participants were followed up from 1st January 2012 to 31st December 2018. Cox proportional hazards model was used to assess the association between the baPWV values and cancer.ResultsDuring a total follow-up duration of 172,775.69 person-years, there were 553 new cases of cancer. The subjects in the highest baPWV group showed an increased risk of cancer when compared with the lowest baPWV group as confirmed by multivariate-adjusted hazard ratios (HR = 1.51, 95% CI = 1.14∼2.00) in the entire cohort. Compared with participants in the lowest baPWV group, the HRs (95% CI) for digestive cancer in the second and third groups were 1.55 (1.00∼2.40) and 1.99 (1.19∼3.33), respectively. The Kaplan-Meier analysis demonstrated a significant increase in cancer in participants with a baPWV ≥ 18 m/s (P ConclusionIncreased arterial stiffness measured by baPWV is associated with cancer occurrence, especially digestive cancer occurrence.Clinical trial registrationClinicalTrials.gov, identifier ChiCTR-TNRC-11001489.</p

Olaparib attenuates the oxLDL-mediated increase in pro-IL-1β and pro-IL-18 protein expression.

THP-1 monocytes were exposed to oxLDL, the PARP inhibitor olaparib (Olapa), or the NLRP3 inhibitor MCC950 (MCC), individually or in combination as indicated. Cell lysates were subjected to SDS-PAGE and immunoblotted with anti-pro-IL-1β (top), anti-pro-IL-18 (middle) or anti-vinculin antibody (bottom, for loading control). The densities of pro-IL-1β, pro-IL-18 over vinculin were quantified by densitometry and normalized to vehicle. The band densities, relative to vinculin, were quantified using ImageJ (NIH, Bethesda, MD). N = 4/group, *P<0.05 vs vehicle, #P<0.05 vs oxLDL only, one-way ANOVA, Newman-Keuls test.</p

Olaparib inhibits oxLDL-induced NIK protein expression and p100 phosphorylation.

The THP-1 monocytes were exposed to oxLDL, the PARP inhibitor olaparib (Olapa), or the NLRP3 inhibitor MCC950 (MCC), as indicated. The cell lysates were subjected to SDS-PAGE and immunoblotted with anti-NIK (top), anti-phospho-p100 (middle) or anti-vinculin antibody (bottom, for loading control), as indicated. The band densities, relative to vinculin, were quantified using ImageJ (NIH, Bethesda, MD). N = 4/group, *P<0.05 vs vehicle, #P<0.05 vs oxLDL only, one-way ANOVA, Newman-Keuls test.</p

MCC950 compound abrogates oxLDL-induced increase in pro-IL-1β protein expression.

THP-1 cells were exposed to oxLDL, the NLRP3 inhibitor MCC950 (MCC) or their combination (MCC+OxL). Cell lysates were subjected to SDS-PAGE and immunoblotted with anti-pro-IL-1β (upper panel) or anti-vinculin antibody (bottom panel), as indicated. The band densities, relative to vinculin (loading control), were quantified using ImageJ (NIH, Bethesda, MD). Veh, vehicle. N = 3/group, * P (TIF)</p

Increased plasma corin levels in patients with atrial fibrillation

BACKGROUND: NPPA mutations/polymorphisms were associated with atrial fibrillation (AF), and plasma proatrial natriuretic peptide (proANP) concentrations were increased in AF patients. Corin, as a transmembrane protease that processes proANP in the heart, may play a potential role in AF. METHODS: To test whether corin concentrations are altered in AF patients, we used ELISA to measure corin and N-terminal proANP (NT-proANP) concentrations in plasma samples from control (n=127) and AF patients (n=141), including paroxysmal AF (PAF, n=83) and persistent AF (PeAF, n=58). RESULTS: In patients with AF, plasma corin concentrations were 1209±510pg/ml, which were significantly higher than in the controls (973±528pg/ml, P<0.001). The increased plasma corin concentrations were found in both male and female patients. Plasma NT-proANP concentrations in AF patients were 3.1±2.42nmol/l, which were higher than in the controls (1.77±1.04nmol/l, P<0.001). Gender (P=0.003), weight (P=0.016) and PR interval (P=0.028) were independent predictors of plasma corin concentrations in AF patients. A positive correlation was found between corin concentrations and left atrial diameter/PR interval in AF patients. CONCLUSION: High plasma corin concentrations in AF patients suggest that corin may play an important role in the pathology of AF

Olaparib inhibits oxLDL-induced increase in NF-κB activity.

The THP-1 monocytes were exposed to oxLDL, the PARP inhibitor olaparib (Olapa), or the NLRP3 inhibitor MCC950 (MCC) as indicated. The cell lysates were subjected to SDS-PAGE and immunoblotted with anti-IKK-α (top), anti-phospho-IκBα (middle) or anti-vinculin antibody (bottom, for loading control), as indicated. The band densities, relative to vinculin, were quantified using ImageJ (NIH, Bethesda, MD). N = 4/group, *P<0.05 vs vehicle, #P<0.05 vs oxLDL only, one-way ANOVA, Newman-Keuls test.</p

Olaparib inhibits oxLDL-mediated NLRP3 inflammasomes activity.

THP-1 monocytic cells were exposed to oxLDL, the PARP inhibitor olaparib (Olapa), or the NLRP3 inhibitor MCC950 (MCC), individually or in combination as indicated. Proteins in cell lysates were detected with anti-NLRP3, anti-ASC, and anti-pro-caspase-1 (pro-CASP1) antibodies, as indicated. The band densities, relative to vinculin (loading control) were quantified using ImageJ (NIH, Bethesda, MD). N = 4/group, * P#P<0.05 vs oxLDL only, one-way ANOVA, Newman-Keuls test.</p