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Patients with acute decompensated heart failure (ADHF) show cardiorenal syndrome type 1 (CRS-1) are more likely to have a poor outcome. However, the current criteria often lead to delayed CRS-1 diagnosis. Therefore, we evaluated the predictive value of plasma proenkephalin (pPENK) and urine NT-proBNP (uNT-proBNP) for early diagnosis of CRS-1 and vulnerable-phase prognosis in ADHF patients. The plasma NT-proBNP (pNT-proBNP), pPENK, and uNT-proBNP were measured in 121 ADHF patients on admission. The plasma neutrophil gelatinase-associated lipocalin (pNGAL) was chosen as the reference. Logistic regression was used to determine the predictors of CRS-1. The area under the receiver operating curves (ROCs) was calculated to assess the early diagnostic value of pNGAL, pPENK, and uNT-proBNP/uCr for CRS-1. To evaluate the prognostic risk of factors for the 90-d outcomes of all ADHF patients, the Cox regression was performed and the cumulative risk curve was plotted. We found that pPENK [OR 1.093 (95% CI 1.022–1.169), p = 0.010; AUROC = 0.899 (95% CI 0.831–0.946)] and uNT-proBNP/uCr ratio [OR 1.015 (95% CI 1.003–1.028), p = 0.012; AUROC = 0.934 (95% CI 0.874–0.971)] could independently predict the occurrence of CRS-1 in hospitalized patients with ADHF. The pPENK [HR 1.014 (95% CI 1.000–1.042), p = 0.044] and uNT-proBNP/uCr ration [HR 0.998 (95% CI 0.997–1.000), p = 0.045] were also independent predictors of the risk of HF readmission or all-cause death 90 d after discharge in ADHF patients. The newly found pPENK and noninvasive test of uNT-proBNP/uCr ratio (pg/nmol) on admission may be two promising novel predictive biomarkers for early diagnosis of CRS-1 occurrence and vulnerable-phase outcomes in ADHF patients. [ABSTRACT FROM AUTHOR]

Background: Aortic aneurysm/dissection (AAD) is now encountered more often because of the increasing prevalence of atherosclerosis and hypertension in the population. Despite many therapeutic improvements, in particular timely and successful surgery, in-hospital mortality rates are still higher. Timely identification of patients at high risk will help improve the overall prognosis of AAD. Since early clinical and radiological signs are nonspecific, there is an urgent need for accurate biomarkers. Smooth muscle 22α (SM22α) is a potential marker for AAD because of its abundant expression in vascular smooth muscle, which is involved in development of AAD. Methods: We prepared three different mouse models, including abdominal aortic aneurysm, neointimal hyperplasia and atherosclerosis. SM22α levels were assessed in serum and vascular tissue of the mice. Next, the relationships between serum SM22α level and vascular lesion were studied in mice. Finally, serum from 41 patients with AAD, 107 carotid artery stenosis (CAS) patients and 40 healthy volunteers were tested for SM22α. Serum levels of SM22α were measured using an enzyme-linked immunosorbent assay (ELISA). Results: Compared with the controls, serum SM22α levels were reduced in the models of aortic aneurysm, neointimal formation and atherosclerosis, and elevated in mice with ruptured aneurysm. Serum SM22α level was negatively correlated with apoptosis rate of vascular smooth muscle cells (VSMC), ratio of intima/ media (I/M) area and plaque size. Patients with AAD had significantly higher serum SM22α levels than patients with only CAS, or normal controls. Conclusion: Serum SM22α could be a potential predictive marker for AAD, and regulation of VSMC is a possible mechanism for the effects of SM22α. [ABSTRACT FROM AUTHOR]

Proteins in Jumonji family function as histone demethylases and participate in cardiac development. Jumonji domain containing 5 (JMJD5) is responsible for the embryonic development through removing methyl moieties from H3K36me2 histone, and has pro‐proliferative effect on heart and eye development. However, the protective role of JMJD5 against oxygen–glucose deprivation and reperfusion (OGD/R)‐induced injury in cardiomyocytes has not been fully understood. Firstly, myocardial ischemia/reperfusion (I/R) rat model was established by ligation of left coronary artery. OGD/R was performed in non‐transfected H9C2 or H9C2 transfected with pcDNA‐JMJD5 plasmid to induce cell cytotoxicity. Data from qRT‐PCR and western blot showed that JMJD5 was reduced in the heart tissues of myocardial I/R rat model and OGD/R‐induced H9C2. Secondly, JMJD5 over‐expression attenuated OGD/R‐induced decrease in cell viability and increase in lactate dehydrogenase secretion and cell apoptosis in H9C2. Mitophagy was promoted by pcDNA‐mediated over‐expression of JMJD5 with enhanced protein expression of LC3‐I, LC3‐II, Atg5, and Beclin 1. Thirdly, knockdown of JMJD5 aggravated OGD/R‐induced decrease in hypoxia‐inducible factor‐1α (HIF‐1α), whereas JMJD5 over‐expression enhanced BNIP3 (Bcl‐2/adenovirus E1B 19‐kDa interacting protein) through upregulation of HIF‐1α. Lastly, BNIP3 silencing promoted cell apoptosis, suppressed mitophagy, and attenuated the protective effects of JMJD5 over‐expression against OGD/R‐induced injury in H9C2. In conclusion, JMJD5 exerted protective effects against OGD/R‐induced injury in cardiomyocytes through upregulation of HIF‐1α‐BNIP3. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRs) have been identified as critical regulatory molecules in myocardial ischemia/reperfusion injury; however, the exact expression profile of miR-199a-5p in reperfusion injury and the underlying pathogenic mechanisms remain unclear. In the present study, it was revealed that miR-199a-5p expression was significantly increased in the plasma of patients with acute myocardial infarction and in a H9c2 cell model of oxygen-glucose deprivation and reperfusion (OGD/R) via reverse transcription-quantitative PCR. H9c2 cells were transfected with miR-199a-5p mimic or inhibitor, or short interfering RNA (siRNA) specific to hypoxia-inducible factor-1α (HIF-1α). MTS, lactate dehydrogenase (LDH), TUNEL staining and flow cytometry assays were performed to determine the proliferation, LDH activity, apoptosis and mitochondrial membrane potential (ΔΨm) of H9c2 cells, respectively. The overexpression of miR-199a-5p in the OGD/R cell model significantly decreased the viability and increased the lactate dehydrogenase leakage of cells; whereas knockdown of miR-199-5p induced the opposing effects. Additionally, inhibition of miR-199-5p significantly attenuated OGD/R-induced alterations to the mitochondrial transmembrane potential (ΔΨm) and increases in the apoptosis of cells. Furthermore, the overexpression or knockdown of miR-199a-5p decreased or increased the expression of HIF-1α and phosphorylation of glycogen synthase kinase 3β (GSK3β) in OGD/R-treated H9c2 cells. Additionally, siRNA-mediated downregulation of HIF-1α decreased phosphorylated (p)-GSK3β (Ser9) levels and reversed the protective effects of miR-199a-5p inhibition on OGD/R-injured H9c2 cells. Similarly, treatment with LiCl (a specific inhibitor of p-GSK3β) also attenuated the protective effects of miR-199a-5p knockdown on OGD/R-injured H9c2 cells. Mechanistic studies revealed that HIF-1α was a target of miR-199a-5p, and that HIF-1α downregulation suppressed the expression of p-GSK3β in OGD/R-injured H9c2 cells. Furthermore, an miR-199a-5p inhibitor increased the interaction between p-GSK3β and adenine nucleotide transferase (ANT), which was decreased by OGD/R. Additionally, miR-199a-5p inhibitor reduced the OGD/R-induced interaction between ANT and cyclophilin D (Cyp-D), potentially leading to the increased mitochondrial membrane potential in inhibitor-transfected OGD/R-injured H9c2 cells. Collectively, the present study identified a novel regulatory pathway in which the upregulation of miR-199a-5p reduced the expression of HIF-1α and p-GSK3β, and potentially suppresses the interaction between p-GSK3β and ANT, thus promoting the interaction between ANT and Cyp-D and potentially inducing cytotoxicity in OGD/R-injured H9c2 cells. [ABSTRACT FROM AUTHOR]

The binding sequences for signal transducer and activator of transcription (STAT) and activator protein 1 have been found in the promoter region of the angiotensinogen gene. We examined whether the elements for activator protein 1 and STAT5B function in angiotensinogen gene activation induced by angiotensin II in vascular smooth muscle cells. Stimulation with angiotensin II increased the level of angiotensinogen mRNA by 2.1-fold in vascular smooth muscle cells. The increased level of angiotensinogen mRNA occurred with concurrent elevations in the levels of STAT5B and c-Jun phosphorylation after stimulation with angiotensin II. Likewise, angiotensin II resulted in similar enhancements of the DNA-binding activity of STAT5B and c-Jun in angiotensin II-induced angiotensinogen expression. Notably, the STAT5B–DNA complex interacted with the c-Jun–DNA complex by forming a stable quaternary complex in angiotensin II-induced angiotensinogen expression. Our findings support a model in which co-operative interaction of STAT5B and activator protein 1 bound to the the promoter region provides maximal activation of angiotensinogen expression by angiotensin II in vascular smooth muscle cells. [ABSTRACT FROM AUTHOR]