ABSTRACT
Objective To study the protective effect of lipoic acid (LA) on H9c2 cardiomyocytes hypoxia/reoxygenation injury model, and explore its relevant mechanism. Methods Eight strains of H9c2 cardiomyocytes, passaged after cultured to a full view, were divided into 3 groups:normoxia group, hypoxia/reoxygenation group and LA group. The cell survival rate, lactate dehydrogenase (LDH) activity, malondialdehyde (MDA) and heme oxygenase-1 (HO-1) levels were detected and compared. Results The cell survival rates of H9c2 cardiomyocytes in hypoxia/reoxygenation group and LA group were significantly lower than those in normoxia group:(52.86 ± 6.39)％, (69.25 ± 7.63)％vs. (92.31 ± 7.82)％, while the cell survival rate of H9c2 cardiomyocytes in LA group was significantly higher than that in hypoxia/reoxygenation group, and there were statistical differences (P<0.01). The LDH activity and MDA in hypoxia/reoxygenation group and LA group were significantly higher than those in normoxia group:(286.37 ± 27.49), (209.72 ± 25.63) U/L vs. (126.32 ± 18.94) U/L, and (1.72 ± 0.06), (1.13 ± 0.07)μmol/L vs. (0.68 ± 0.06) μmol/L, while those data in LA group were significantly lower than those in hypoxia/reoxygenation group, and there were statistical differences (P<0.01). The HO-1 in hypoxia/reoxygenation group and LA group were significantly higher than that in normoxia group:(213.71 ± 18.94)％, (367.26 ± 23.07)％vs. (87.92 ± 19.23)％, and HO-1 in LA group was significantly higher than that in hypoxia/reoxygenation group, and there were statistical differences (P<0.01). Conclusions The LA plays a protective role on myocardial cell with hypoxia/reoxygenation injurythough increasing the level of HO-1 against oxidative stress.
ABSTRACT
Long non-coding RNA plays an increasingly important role in transcriptional, post-transcriptional and epigenetic levels. In ischemic heart disease, most studies on long non-coding RNA focused on myocardial infarction, hypertrophy and fibrosis, and a few of reports directly focused on the pathological process of myocardial reperfusion injury. Thus, the purpose of this review is to introduce the processes of long non-coding RNA in myocardial reperfusion injury field, aiming to provide a novel research and theraputic method for exploring the mechanism and molecular regulation network involed with reperfusion injury.
ABSTRACT
AIM: Mutations in lipoprotein-associated phospholipase A2 (Lp-PLA2) are related to atherosclerosis. However, the molecular effects of Lp-PLA2 on atherosclerosis have not been fully investigated. Therefore, this study attempted to elucidate this issue. METHODS: Monocytes were isolated from randomly selected healthy male volunteers according to each Lp-PLA2 genotype (wild-type Lp-PLA2 [Lp-PLA2 (V/V)], the heterozygous V279F mutation [LpPLA2 (V/F)] and the homozygous V279F mutation [Lp-PLA2 (F/F)]) and differentiated into macrophages. The level of apoptosis in the macrophages following incubation without serum was measured using the annexin V/propidium iodide double staining method, and the underlying mechanisms were further examined using a culture cell line. RESULTS: The average plasma Lp-PLA2 concentration [Lp-PLA2 (V/V): 129.4 ng/mL, Lp-PLA2 (V/F): 70.7 ng/mL, Lp-PLA2 (F/F): 0.4 ng/mL] and activity [Lp-PLA2 (V/V): 164.3 nmol/min/mL, LpPLA2 (V/F): 100.9 nmol/min/mL, Lp-PLA2 (F/F): 11.6 nmol/min/mL] were significantly different between each genotype, although the basic clinical characteristics were similar. The percentage of apoptotic cells was significantly higher among the Lp-PLA2 (F/F) macrophages compared with that observed in the Lp-PLA2 (V/V) macrophages. This induction of apoptosis was independent of the actions of acetylated low-density lipoproteins. In addition, the transfection of the expression plasmid of V279F mutant Lp-PLA2 into Cos-7 cells or monocyte/macrophage-like U937 cells promoted apoptosis. The knockdown of Lp-PLA2 also increased the number of apoptotic cells. Among the cells expressing mutant Lp-PLA2, the caspase-7 activity was increased, while the activated Akt level was decreased. CONCLUSIONS: The V279F mutation of Lp-PLA2 positively regulates the induction of apoptosis in macrophages and Cos-7 cells. An increase in the caspase-7 activity and a reduction in the activated Akt level are likely to be involved in this phenomenon.