Association of Plasma MiRNA-204 and the Presence and Severity of Coronary Artery Calcification in Patients With Type 2 Diabetes.

We investigated the association between plasma microRNA (miR)-204 and coronary artery calcification (CAC) in patients with type 2 diabetes mellitus (T2DM). We consecutively enrolled 179 individuals with T2DM who underwent coronary computed tomography at Anzhen Hospital from January 2015 to September 2016. The CAC score (CACS) was expressed in Agatston units and >10 Hounsfield units were defined as CAC-positive status. Significant CAC was observed in 98 (54.7%) patients. Plasma miR-204 levels (relative expression) were significantly lower in patients with significant CAC than controls (1.001 ± 0.100 vs 0.634 ± 0.211, P < .001). Plasma miR-204 levels were also negatively correlated with the glycosylated hemoglobin A1c (HbA1c) level (r = -0.702, P < .001), CACS (r = -0.710, P < .001), and the United Kingdom Prospective Diabetes Study (UKPDS) score (r = -0.355, P < .001). After multivariate logistic analyses, plasma miR-204 levels were still significantly and independently associated with the presence of CAC (odds ratio = 0.103, CI = 0.018-0.583, P < .001) after adjustment for conventional risk factors. Receiver operating characteristic curve analysis showed that plasma miR-204 levels can predict the severity and extent of CAC, and the specificity was higher than that of the traditional risk factors UKPDS score and HbA1c. In conclusion, the downregulation of miR-204 was independently associated with CAC in patients with T2DM.

Serum microRNA-204 levels are associated with long-term cardiovascular disease risk based on the Framingham risk score in patients with type 2 diabetes: results from an observational study.

BACKGROUND: Previous studies have demonstrated that microRNA-204 (miR-204) is involved in atherosclerosis and vascular calcification. However, the value of miR-204 as the predictive biomarker for cardiovascular disease (CVD) remains unclear. We aimed to evaluate the association between the circulating miR-204 level and ten-year CVD risk based on the Framingham risk score (FRS). METHODS: In this retrospective study, we enrolled 194 consecutive patients with type 2 diabetes mellitus (T2DM) without CVD in Beijing Anzhen Hospital between January 2015 and September 2016. We used the FRS to evaluate the risk of CVD for each patient. Circulating miR-204 levels were measured by quantitative real-time polymerase chain reaction. RESULTS: Circulating miR-204 levels were significantly lower in the group of patients (0.49 ± 0.13) at high risk of CVD (FRS > 20%) than in the low (FRS < 10%) and intermediate (FRS: 10%-20%) risk groups (0.87 ± 0.19 and 0.75 ± 0.25, respectively; P < 0.001). FRS was negatively correlated with miR-204 levels (r = -0.421, P < 0.001). According to multivariate logistic analyses, reduced miR-204 level was independently associated with an increased risk of CVD after adjusting for conventional risk factors (OR = 0.876, 95% CI: 0.807-0.950, P = 0.001). Receiver-operating characteristic curve analysis showed that the circulating miR-204 level can predict the high risk of CVD with higher specificity than the traditional risk factor of high systolic blood pressure or the protective factor of high-density lipoprotein cholesterol. CONCLUSIONS: Our study demonstrated that patients with lower circulating miR-204 levels were at high risk for CVD. After adjustment for potential confounders, miR-204 was independently associated with CVD in patients with T2DM.

Increased plasma lipoprotein-associated phospholipase A2 levels are associated with coronary slow flow.

OBJECTIVE: Coronary slow flow (CSF) is characterized by delayed opacification of distal epicardial coronary arteries without significant coronary stenosis. In addition, The changes of lipoprotein-associated phospholipase A2 (Lp-PLA2) as a significant predictive factor for CSF remain controversial. The study aims to investigate the association between plasma Lp-PLA2 and CSF. METHODS: In this retrospective study, 170 consecutive patients who underwent coronary angiography were enrolled in Beijing Anzhen Hospital from January 2017 to September 2019, and were divided into CSF group and normal control groups. According to coronary blood flow rate measured by the thrombolysis in myocardial infarction frame count (TFC) method, CSF was defined as TFC > 27. Serum Lp-PLA2 levels were measured in an enzyme-linked immunosorbent assay. RESULTS: Lp-PLA2 levels were higher in the CSF group than in the control group (288.6 ± 50.3 versus 141.9 ± 49.7, P < 0.001) and were significantly correlated with the mean coronary artery thrombolysis in myocardial infarction (TIMI) frame count (r = 0.790, P<0.001). Logistic regression analysis showed that high Lp-PLA2 was independently associated with CSF after adjustment for conventional risk factors (OR = 1.040, CI = 1.022-1.059, P<0.001). Male sex (OR = 2.192, CI = 1.161-4.140, P = 0.016) and hypertension (OR = 1.965, CI = 1.034-3.736, P = 0.039) were also CSF risk factors. Receiver-operating characteristic curve (ROC) analysis showed that Lp-PLA2 levels can predict CSF severity; the predictive power was higher than the other risk factors. CONCLUSION: Our study demonstrated that patients with CSF had higher circulating levels of Lp-PLA2 than normal controls. After adjustment for potential confounders, increased Lp-PLA2 was independently associated with presence of CSF.

Triptolide Attenuates Vascular Calcification by Upregulating Expression of miRNA-204.

Background: Triptolide (TP), a naturally derived compound from Tripterygium wilfordii, has been proven effective in protecting against cardiovascular system, but the molecular mechanisms underlying its protective effects are poorly understood. In the current study, we sought to test the potential protective role of TP in the regulation of vascular calcification in a rat model and explore whether TP attenuates medial vascular calcification by upregulating miRNA-204. Methods: Vitamin D3 plus nicotine (VDN) was used to induce a vascular calcification (VC) model of rat aorta. Von Kossa and Hematoxylin-Eosin staining were applied to assess the degree of calcification of rat aortas. Calcium content and alkaline phosphatase activity were measured. Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was applied to quantify miRNA-204 expression. The localization of runt-related transcription factor-2 (RUNX2) and bone morphogenetic protein-2 (BMP2) expressions were detected by immunohistochemistry and western blotting. Results: Administration of TP greatly reduced vascular calcification in a dose-dependent manner compared with VC controls. The increase in ALP activity and calcium content was ameliorated by TP. Moreover, protein expression levels of BMP2 and RUNX2 were significantly reduced in calcified aortas. MiRNA-204 expression was increased in the TP-treated groups compared with VC controls and the effects of TP were reversed by the intravenous injection of miRNA-204-interfering lentivirus. However, the miRNA-204-overexpressing lentivirus had no additional effects on ALP activity, calcium content, BMP2 and RUNX2 expressions compared with those from TP group. Conclusion: TP inhibited BMP2 and RUNX2 expression and attenuated vascular calcification via upregulating the level of miRNA-204. TP appears to be a potential new therapeutic option for treating vascular calcification.