ALDH2 Gene rs671 Polymorphism May Decrease the Risk of Essential Hypertension.

Aldehyde dehydrogenase-2 (ALDH2) rs671 G>A polymorphism can influence the activity of ALDH2 and may be associated with the risk of essential hypertension (EH). Although many previous studies have explored such a relationship, the conclusion is still controversial.The PubMed, Embase, and China National Knowledge Infrastructure databases were searched on the ALDH2 gene and EH. We used the Newcastle-Ottawa Scale to evaluate the quality of the study. Then we calculated the strength of relationship between ALDH2 rs671 mutation and EH by utilizing odds ratios and 95% confidence intervals. Besides, subgroup analysis and sensitivity analysis were performed and the publication bias was assessed.There were 12 studies containing 8153 cases and 10,162 controls. Our meta-analysis showed significant association between ALDH2 rs671 polymorphism and EH in four genetic models (the allele model, the homozygote model, the heterozygote model, and the dominant model), whereas it did not indicate this connection in the recessive model. However, a trend of decreased risk still could be seen. Furthermore, we also found an obvious association between rs671 mutation and the risk of EH in the male group than in the female group in all five genetic models.We concluded that ALDH2 rs671 G>A polymorphism may decrease the risk of EH. Furthermore, susceptibility to EH reduced in males but not in females. As a variant in ALDH2, rs671 G>A could be an attractive candidate for genetic therapy of EH. In addition, more case-control studies should be conducted to strengthen our conclusion and evaluate the gene-gene and gene-environment interactions between the ALDH2 gene and EH.

[Impact and related mechanisms of stromal cell-derived factor-1α on serum deprivation-induced cardiac stem cells apoptosis].

OBJECTIVE: To explore the impact and related mechanisms of stromal cell-derived factor-1α (SDF-1α) on serum deprivation-induced apoptosis of cardiac stem cells (CSCs). METHODS: CSCs were isolated from adult mouse heart tissue and cultured in vitro. Obtained cells were purified using magnetic-activated cell sorting (MACS) with c-kit magnetic beads. C-kit(+)CSCs were divided into five groups: normal control group, serum deprivation group, serum deprivation+SDF-1α group, serum deprivation+SDF-1α+AMD3100 group, serum deprivation+SDF-1α+LY294002 group. Cell apoptosis was assessed using the DeadEnd Colorimetric TUNEL System and flow cytometry analyses with an Annexin V-FITC Apoptosis Detection Kit. The viability of CSCs was assessed by CCK-8. The protein expression of Bcl-2 and phosphorylated Akt were detected by Western blot. The caspase-3 activity was determined using caspase-3 Colorimetric Assay Kit. RESULTS: After magnetic separation, more than 85% of cardiosphere derived cells were positive for c-kit expression. Compared with the normal control group, the apoptosis rate of serum deprivation group was significantly increased[(27.03 ± 0.80)% vs. (1.51 ± 0.54)%, P < 0.01], which could be significantly reduced by SDF-1α in a concentration dependent manner and peak effect was seen with 100 ng/ml SDF-1α[(10.67 ± 1.06)% vs. (27.03 ± 0.80)%, P < 0.01]. The expressions of p-Akt and Bcl-2 were significantly increased and the activity of caspase-3 was significantly decreased in serum deprivation+SDF-1α group compared to serum deprivation group (P < 0.01). Further more, the expression of p-Akt and Bcl-2 were significantly decreased and the activity of caspase-3 was increased in both serum deprivation+SDF-1α+AMD3100 group and serum deprivation+SDF-1α+LY294002 group compared to serum deprivation+SDF-1α group (P < 0.01). CONCLUSIONS: SDF-1α reduces serum deprivation induced CSCs apoptosis via modulating PI3K/Akt signaling pathway.

hAECs and their exosomes improve cardiac function after acute myocardial infarction in rats.

BACKGROUND: Human amniotic epithelial cells (hAECs) are seed cells used to treat acute myocardial infarction (AMI), but their mechanism remains unclear. METHODS: We cultured hAECs and extracted exosomes from culture supernatants. Next, we established a stable AMI model in rats and treated them with hAECs, exosomes, or PBS. We assess cardiac function after treatment by echocardiography. Additionally, heart tissues were collected and analyzed by Masson's trichrome staining. We conducted the tube formation and apoptosis assays to explore the potential mechanisms. RESULTS: Cardiac function was improved, and tissue fibrosis was decreased following implantation of hAECs and their exosomes. Echocardiography showed that the EF and FS were lower in the control group than in the hAEC and exosome groups, and that the LVEDD and LVESD were higher in the control group (P<0.05). Masson's trichrome staining showed that the fibrotic area was larger in the control group. Tube formation was more efficient in the hAEC and exosome groups (P<0.0001). Additionally, the apoptosis rates of myocardial cells in the hAEC and exosome groups were significantly decreased (P<0.0001). CONCLUSIONS: hAECs and their exosomes improved the cardiac function of rats after AMI by promoting angiogenesis and reducing the apoptosis of cardiac myocytes.

Correlation of left atrial strain with left ventricular end-diastolic pressure in patients with normal left ventricular ejection fraction.

Left ventricular diastolic dysfunction (LVDD) remains challenging to be assessed by echocardiography. We sought to explore the relationship between left atrial strain and left ventricular (LV) diastolic function in patients with normal left ventricular ejection fraction (LVEF) by invasive left-heart catheterization. 55 consecutive individuals with LVEF > 50% underwent LV catheterization. Standard transthoracic echocardiography was performed during 12 h before or after the procedure. Left atrial (LA) strain were obtained by speckle tracking echocardiography. When LVEF ≥ 50%, the group with elevated left ventricular end-diastolic pressure (LVEDP) (n = 35) showed decreased left atrial reservoir strain (LASr) (35.2 ± 7.7% vs 21.3 ± 7.2%, p < 0.001), left atrial conduit strain (LASct) (17.6 ± 6.3% vs 11.9 ± 4.1%, p < 0.001), left atrial contraction strain (LAScd) (16.6 ± 7.2% vs 9.5 ± 5.0%, p < 0.001) and increased E/e' ration(8.9 ± 2.6 vs 10.1 ± 3.5, p = 0.17). LVEDP negatively correlated with LASr (R = 0.662, p < 0.001), LASct (R = 0.575, p < 0.001) and LAScd (R = 0.456, p < 0.001), but not with E/e'. LASr, LASct and LAScd were all independent predictors of elevated LVEDP (p < 0.05), with a higher C-statistic for the model including LASr (0.95, 0.86 and 0.93 respectively). The area under the curve (AUC) for LASr is 0.914 (cutoff value is 26.7%, sensitivity is 90%, specificity is 82.9%). In patients with normal LV ejection fraction, left atrial strain presented good correlation with LVEDP, and LASr was superior to LASct and LAScd to predict LVEDP. LA strain demonstrated better agreement with the invasive reference than E/e'.