[Association of RAGE gene polymorphisms with MHR ratio and heart rate variability among patients with coronary heart disease].

OBJECTIVE: To assess the association of polymorphisms of receptor of advanced glycation end products (RAGE) gene, monocyte to high-density lipoprotein cholesterol ratio (MHR) and variability of heart rate among patients with coronary heart disease (CHD). METHODS: 120 patients with CHD and 120 healthy individuals were respectively selected as the observation group and the control group. Allelic and genotypic differences of -429T>C, 1704G>T, 82G>S, MHR ratio and heart rate variability between the two groups and patients with different severity were analyzed. The correlation between their genotypes and MHR ratio and heart rate variability was analyzed. RESULTS: The 82G>S polymorphism of the RAGE gene and the allelic difference between the two groups and patients with different severity were statistically significant (P< 0.05). Compared with the control group and patients with mild to moderate phenotype, monocyte, total cholesterol, triglyceride, low density lipoprotein, MHR, low frequency in the observation group and patients with severe symptoms were significantly higher, while their high density lipoprotein, standard deviation of NN intervals (SDNN), standard deviation average of NN intervals (SDANN), root mean square successive differences, percentage of differences exceeding 50ms between adjacent normal number of intervals (PMN50), high frequency (HF) were significantly lower. The gene frequencies of G-Gly-T, T-Gly-T, G-Ser-T and G-Gly-C were correlated with SDNN, SDANN, rMSSD, PMN50, HF and MHR, but negatively correlated with low frequency. CONCLUSION: Polymorphisms of the RAGE gene in patients with coronary heart disease are associated with the MHR ratio and heart rate variability, which can be used as markers for the diagnosis and efficacy evaluation.

Paeonol suppresses the effect of ox-LDL on mice vascular endothelial cells by regulating miR-338-3p/TET2 axis in atherosclerosis.

Atherosclerosis is the common vascular disease. Vascular smooth muscle cell proliferation and vascular endothelial cell (VEC) dysfunction are involved in the causes of atherosclerosis. And oxidized low-density lipoprotein (ox-LDL)-induced vascular endothelial cells (VECs) are suitable models for studying atherosclerosis development. Paeonol was reported to repress ox-LDL-induced VEC progression. However, its detailed mechanism was not fully reported. MicroRNAs (miRNAs) acted as regulators in multiple diseases. Previous findings found that microRNA-338-3p (miR-338-3p) was overexpressed in Atherosclerosis process. However, the function and underlying mechanism of miR-338-3p in ox-LDL-treated VECs needed to be elucidated. The purpose of this research was to reveal the role of miR-338-3p in paeonol-regulated ox-LDL-induced VEC progression. Cell counting kit-8 (CCK-8) and flow cytometry were employed to determine cell viability and apoptosis, respectively. Moreover, the levels of IL-6 and IL-1ß were analyzed using enzyme-linked immunosorbent assay, as well as the contents of reactive oxygen species, lactate dehydrogenase, and malonic dialdehyde were investigated using related kits. Furthermore, quantitative real-time polymerase chain reaction was carried out to determine the expression of miR-338-3p. Western blot assay was conducted to detect the level of tet methylcytosine dioxygenase 2 (TET2). Besides, the interaction between miR-338-3p and TET2 was predicted by DIANA, and then confirmed by the dual-luciferase reporter assay and RNA immunoprecipitation assay. Ox-LDL repressed mice VEC viability, and promoted apoptosis, inflammatory response, and oxidative injury. Paeonol inhibited the effect of ox-LDL on the growth of the VECs. Furthermore, paeonol regulated VEC development via downregulating miR-338-3p expression. Interestingly, miR-338-3p targeted TET2 and inhibited TET2 expression. MiR-338-3p modulated ox-LDL-treated VEC growth through suppressing TET2 expression. We demonstrated that paeonol attenuated the effect of ox-LDL on the development of mice VECs via modulating miR-338-3p/TET2 axis, providing a theoretical basis for the treatment of AS.

Xanthoangelol Prevents Ox-LDL-Induced Endothelial Cell Injury by Activating Nrf2/ARE Signaling.

OBJECTIVE: Atherosclerosis (AS) contributes to the development of several cardiovascular diseases such as myocardial infarction and stroke. Oxidized low-density lipoprotein (Ox-LDL)-induced endothelial cell injury plays a key role in the pathogenesis of AS. Thus, this study was conducted to examine the effects of a naturally occurring flavonoid compound, xanthoangelol (XAG), on Ox-LDL-induced cell injury. MATERIALS AND METHODS: Human umbilical vein endothelial cells (HUVECs) were used as the in vitro cell model. The number of viable cells was determined using CCK-8 assay. Cell apoptosis was detected using Hoechst staining. Percentage of apoptotic cells was quantified by flow cytometry. The cellular levels of malondialdehyde (MDA), superoxide dismutase, catalase (CAT), and glutathione peroxidase were determined using enzyme-linked immunosorbent assays. The cellular reactive oxygen species level was detected by flow cytometry after fluorescence staining. The mRNA expression levels of nuclear factor-E2-related factor-2 (Nrf2), heme oxygenase-1 (HO-1), and NQO-1 were determined using quantitative real-time polymerase chain reaction assay. The protein levels of cleaved caspase-3, cleaved poly ADP-ribose polymerase, Bax, Bcl-2, Nrf2, Keap1, HO-1, and NQO-1 were measured by using Western blot assay. The HUVECs were transfected with Nrf2 siRNA to reduce the expression of Nrf2. RESULTS: XAG could effectively protect against Ox-LDL-stimulated cell death in HUVECs. These cytoprotective effects were due to its anti-apoptotic and anti-oxidant activities, as supported by the increase of SOD, CAT, and glutathione peroxidase activities, and the decrease of MDA and reactive oxygen species levels in injured HUVECs induced by Ox-LDL. Moreover, the results showed that XAG activated Nrf2/ARE signaling in a dose-dependent manner. Importantly, blockade of Nrf2 signaling using siRNA or specific inhibitor notably abolished the cytoprotective activities of XAG. CONCLUSIONS: These data suggest that XAG cytoprotects against Ox-LDL-induced cell injury through activating Nrf2/ARE-mediated antioxidative stress. Cumulatively, these findings show that EX has the potential to prevent and treat AS.