Background: Hyperlipidemia plays a crucial role in the development and progression of coronary artery disease (CAD). Recent studies have identified that microRNAs (miRNAs) are important regulators of lipid metabolism, but little is known about the circulating levels of lipometabolism-related miRNAs and their relationship with the presence of CAD in patients with hyperlipidemia. Methods: In the present study, we enrolled a total of 255 hyperlipidemia patients with or without CAD and 100 controls with normal blood lipids. The plasma levels of four known lipometabolism-related miRNAs, miR-122, miR-370, miR-33a, and miR-33b were quantified by real-time quantitative PCR. Blood levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), and high density lipoprotein cholesterol were determined. Furthermore, the severity of CAD was assessed with the Gensini score system based on the degree of luminal narrowing and its geographic importance. Results: Our results revealed for the first time that plasma levels of miR-122 and miR-370 were significantly increased in hyperlipidemia patients compared with controls, and the levels of miR-122 and miR-370 were positively correlated with TC, TG, and LDL-C levels in both hyperlipidemia patients and controls. Multiple logistic regression analysis demonstrated that the increased levels of miR-122 and miR-370 were associated with CAD presence, even after adjustment for other cardiovascular risk factors. Furthermore, miR-122 and miR-370 levels were positively correlated with the severity of CAD quantified by the Gensini score. However, both miR-33a and miR-33b were undetectable in plasma. Conclusions: Our results suggest that increased plasma levels of miR-122 and miR-370 might be associated with the presence as well as the severity of CAD in hyperlipidemia patients.

Recent studies in animal models and humans show that long non-coding RNAs (lncRNAs) are involved in the development of atherosclerosis, which contributes to the pathological foundation of coronary artery disease (CAD). LncRNAs in plasma and serum have been considered as promising novel biomarkers for diagnosis and prognosis of cardiovascular diseases, especially CAD. We here measured the circulating levels of 8 individual lncRNAs which are known to be relevant to atherosclerosis in the plasma samples from 300 patients with CAD and 180 control subjects by using quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) methods. We found that the plasma level of H19 and long intergenic non-coding RNA predicting cardiac remodeling (LIPCAR) were significantly increased in patients with CAD. The area under the receiver operating characteristic curve was 0.631 for H19 and 0.722 for LIPCAR. Multivariate logistic regression analyses indicated that plasma H19 and LIPCAR were independent predictors for CAD, even after adjustment for traditional cardiovascular risk factors. Further studies identified that plasma levels of H19 and LIPCAR were also increased in CAD patients with heart failure compared to those with normal cardiac function. Taken together, our results suggest that increased plasma levels of H19 and LIPCAR are associated with increased risk of CAD and may be considered as novel biomarkers for CAD.

Background: Epidemiologic studies are inconsistent regarding the association between tea consumption and the risk of coronary artery disease (CAD).Ob

Background: Mesenchymal stem cells (MSCs)-based regenerative therapy is currently regarded as an alternative approach to salvage the acute myocardial infarcted hearts. However, the efficiency of MSCs transplantation is limited by lower survival rate of engrafted MSCs. In previous study, we found that 1.0 μg/ml Lipopolysaccharide (LPS) could protect MSCs against apoptosis induced by oxidative stress and meanwhile enhance the proliferation of MSCs. Therefore, in the present study, we firstly preconditioned MSCs with 1.0 μg/ml LPS, then transplanted MSCs into ischemic myocardium, and observed the survival and cardiac protective capacity of MSCs in a rat model of acute myocardial infarction. Furthermore, we tried to explore the underlying mechanisms and the role of Toll-like receptor-4 (TLR4) in the signal pathway of LPS-induced cardiac protection. Methods and results: Acute myocardial infarction model was developed by left anterior descending coronary artery ligation. 60 rats were divided into 4 groups randomly and given an intramyocardial injection of one of the following treatments: 30 μl PBS (control group), 3 × 10⁶ wild MSCs/30 μl (wMSCs group), 3 × 10⁶ LPS-preconditioned wild MSCs/30 μl (LPS-wMSCs group), or 3 × 10⁶ LPS-preconditioned TLR4 gene deleted MSCs/30 μl (LPS-tMSCs group). After 3 weeks, LPS-preconditioned wild MSCs transplantation ameliorated cardiac function and reduced fibrosis of infarcted myocardium. Vascular density was markedly increased in LPS-wMSCs group compared with other three groups. Survival rate of engrafted MSCs was elevated and apoptosis of myocardium was reduced in infarcted heart. Expression of vascular endothelial growth factor (VEGF) and phospho-Akt was increased in the infarcted myocardium after transplantation of LPS-preconditioned MSCs. Conclusion: LPS preconditioning enhanced survival of engrafted MSCs, stimulated expression of VEGF and activated PI3K/Akt pathway. LPS preconditioning before MSCs transplantation resulted in superior therapeutic neovascularization and recovery of cardiac function. LPS preconditioning provided a novel strategy in maximizing biologic and functional properties of MSCs.

Background: In mammals, regenerative therapy after myocardial infarction is hampered by the limited regenerative capacity of adult heart, whereas a transient regenerative capacity is maintained in the neonatal heart. Systemic phosphorylation signaling analysis on ischemic neonatal myocardium might be helpful to identify key pathways involved in heart regeneration. Our aim was to define the kinase-substrate network in ischemic neonatal myocardium and to identify key pathways involved in heart regeneration after ischemic insult. Methods: Quantitative phosphoproteomics profiling was performed on infarct border zone of neonatal myocardium, and kinase-substrate network analysis revealed 11 kinases with enriched substrates and upregulated phosphorylation levels, including checkpoint kinase 1 (CHK1) kinase. The effect of CHK1 on cardiac regeneration was tested on Institute of Cancer Research CD1 neonatal and adult mice that underwent apical resection or myocardial infarction. Results: In vitro, CHK1 overexpression promoted whereas CHK1 knockdown blunted cardiomyocyte proliferation. In vivo, inhibition of CHK1 hindered myocardial regeneration on resection border zone in neonatal mice. In adult myocardial infarction mice, CHK1 overexpression on infarct border zone upregulated mammalian target of rapamycin C1/ribosomal protein S6 kinase b-1 pathway, promoted cardiomyocyte proliferation, and improved cardiac function. Inhibiting mammalian target of rapamycin activity by rapamycin blunted the neonatal cardiomyocyte proliferation induced by CHK1 overexpression in vitro. Conclusions: Our study indicates that phosphoproteome of neonatal regenerative myocardium could help identify important signaling pathways involved in myocardial regeneration. CHK1 is found to be a key signaling responsible for neonatal regeneration. Myocardial overexpression of CHK1 could improve cardiac regeneration in adult hearts by activating the mammalian target of rapamycin C1/ribosomal protein S6 kinase b-1 pathway. Thus, CHK1 might serve as a potential novel target in myocardial repair after myocardial infarction.