MicroRNAs (miRNAs) are small, non-coding, RNA molecules approximately 22 nucleotides in length which act as post-transcriptional regulators of gene expression. Individual miRNAs have been shown to regulate the expression of multiple genes. Conversely, the expression of individual genes can be regulated by multiple miRNAs. Consequently, since their discovery just over 20 years ago, miRNAs have been identified as key regulators of complex biological processes linked to multiple cardiovascular pathologies, including left ventricular hypertrophy, ischaemic heart disease, heart failure, hypertension and arrhythmias. Furthermore, since the finding that miRNAs are present in the circulation, they have been investigated as novel biomarkers, especially in the context of acute myocardial infarction (AMI) and heart failure. While there is little convincing evidence that miRNAs can outperform traditional biomarkers, such as cardiac troponins, in the diagnosis of AMI, there is potential for miRNAs to complement existing risk prediction models and act as valuable markers of post-AMI prognosis. Encouragingly, the concept of miRNA-based therapeutics is developing, with synthetic antagonists of miRNAs (antagomiRs) currently in phase II trials for the treatment of chronic hepatitis C virus infection. In the cardiovascular field, promising preclinical studies suggest that they could be useful in treating disorders ranging from heart failure to dyslipidaemia, although several challenges related to specificity and targeted delivery remain to be overcome. Through this review, we provide clinicians with a brief overview of the ever-expanding world of miRNAs.

https://heart.bmj.com/content/heartjnl/101/12/921.full.pdf

MicroRNAs in cardiovascular disease: an introduction for clinicians

Role of phytochemicals in the management of metabolic syndrome

Vascular smooth muscle cells (VSMCs) are involved in all stages of the progression of human atherosclerosis (AS). MicroRNAs (miRNAs or miRs) are non‑coding, small RNAs that regulate gene expression at the post‑transcriptional level through translational repression or messenger RNA (mRNA) decay. Recently, a variety of functions of VSMCs that are involved in AS, including differentiation, migration, proliferation, extracellular matrix (ECM) synthesis and apoptosis, have been found to be regulated by miRNAs. This review provides an overview of the role of miRNAs in the regulation of the functions of VSMCs, as well as their targets and potential implications in AS. The data presented herein suggest that the specific modulation of miRNAs may present an attractive approach for the diagnosis and treatment of AS.

/pdf/micrornas-regulate-vascular-smooth-muscle-cell-functions-in-2brzldiqci.pdf

MicroRNAs regulate vascular smooth muscle cell functions in atherosclerosis (Review)

Introduction Low vitamin D status has been found to be associated with impaired glycemic control in patients who suffer from type 2 diabetes; however, whether vitamin D supplementation is associated with improved glycemic status remains controversial The aim of this study was to summarize evidence from randomized controlled trials (RCTs) to assess the efficacy of vitamin D supplementation in reducing glycosylated haemoglobinA1c (HbA1c) and fasting blood glucose (FBG) levels Materials/Methods We searched PubMed, Web of Science and the Cochrane Library for reports published up to March 2017 We selected parallel RCTs investigating the effect of vitamin D or vitamin D analogues on HbA1c or FBG levels in type 2 diabetes patients Cohen's d was calculated to represent the standardized mean difference (SMD) for each study, and the SMDs with 95%confidence intervals (CIs) were pooled using a random effects model Results Twenty-four studies were included that evaluated HbA1c levels and 18 studies were included that evaluated FBG levels Meta-analyses showed that vitamin D supplementation was associated with reduced HbA1c levels (standardized mean difference (SMD) − 025 [− 045 to − 005]) but had no influence on FBG levels (SMD − 014 [− 031 to 003]) However, the subgroup analyses suggested that vitamin D supplementation was associated with reduced HbA1c levels (SMD − 039 [− 067 to − 010]) and FBG (SMD − 027 [− 046 to − 007]) among patients with 25-hydroxyvitamin D (25(OH) D) deficiency at baseline Significantly reduced HbA1c levels were also observed in association with vitamin D supplementation in the subgroup including type 2 diabetes patients with a body mass index (BMI) Conclusions Vitamin D supplementation could be effective at improving glycemic control in vitamin D deficient or non-obese type 2 diabetes patients

Vitamin D supplementation and glycemic control in type 2 diabetes patients: A systematic review and meta-analysis.

Endothelial cells (EC) and vascular smooth muscle cells (VSMC) are the main cell types within the vasculature. We describe here how microRNAs (miRs)—noncoding RNAs that can regulate gene expression via translational repression and/or post-transcriptional degradation—distinctively modulate EC and VSMC function in physiology and disease. In particular, the specific roles of miR-126 and miR-143/145, master regulators of EC and VSMC function, respectively, are deeply explored. We also describe the mechanistic role of miRs in the regulation of the pathophysiology of key cardiovascular processes including angiogenesis, atherosclerosis, and in-stent restenosis post-angioplasty. Drawbacks of currently available therapeutic options are discussed, pointing at the challenges and potential clinical opportunities provided by miR-based treatments.

microRNAs Distinctively Regulate Vascular Smooth Muscle and Endothelial Cells: Functional Implications in Angiogenesis, Atherosclerosis, and In-Stent Restenosis

Aims Oxidized low-density lipoprotein (ox-LDL) can induce vascular smooth muscle cell (VSMC) proliferation and differentiation, which is the important mechanism of the pro-atherogenic effects of ox-LDL. Although miRNAs are crucial regulators of the ox-LDL effects on VSMC, the detailed mechanisms are not fully elucidated. So, we investigated the miRNAs changes in the proliferation of human coronary artery smooth muscle cells (hCASMCs) induced by ox-LDL and the functional significance of some miRNAs, which were regulated significantly.

Methods and results Using miRNA microarray, real-time PCR, and luciferase reporter assay, our study showed that miR-490-3p and insulin-like growth factor-1 (IGF1) expression were down-regulated, whereas pregnancy-associated plasma protein A (PAPP-A) and IGF2 expression were up-regulated significantly in hCASMC treated by ox-LDL and/or in human atherosclerotic plaque. Further studies indicated PAPP-A was the target gene of miR-490-3p. The miR-490-3p mimic could inhibit the up-regulation of PAPP-A induced by ox-LDL in hCASMC, which resulted in the suppression of the metalloprotease effect of PAPP-A on IGF-binding protein-4 (IGFBP-4). All these effects led to the inhibition of the proliferation of hCASMC induced by ox-LDL.

Conclusion Ox-LDL could inhibit the expression of miR-490-3p and IGF1, whereas increase IGF2 expression. The inhibition of miR0-490-3p up-regulated its target gene PAPP-A and then increased the proteolysis of IGFBP-4. The increased expression of IGF2 and proteolysis of IGFBP-4 might activate pathways independent or dependent on IGF axis by autocrine and paracrine mechanisms and resulted in the VSMC proliferation. Our results could help us to understand the mechanisms of the pro-atherogenic effects of ox-LDL and the effects of PAPP-A on atherosclerosis development.

MiR-490-3p modulates the proliferation of vascular smooth muscle cells induced by ox-LDL through targeting PAPP-A

Objective
To explore the effects of oral vitamin D supplementation on anthropometric parameters and insulin resistance (IR) in type 2 diabetes mellitus (T2DM).


Methods
A total of 164 subjects with T2DM, aged 30-75 years, were randomly divided into two groups of intervention and control. The intervention group received a daily dose of 0.50 μg calcitriol while the control group maintained the original treatment regimen. At the beginning and end of 12-week supplementation trial, the demographic and anthropometric data were recorded and the serum levels of glucose, insulin, HbA1C and 25(OH)D measured. IR was assessed by the homeostasis model approximation index.


Results
There was no significant inter-group difference at baseline. Compared with the baseline level, body mass index(BMI)((-0.7±1.7) vs (-0.4±1.4) kg/m2)(P 30 ng/ml group ((5±3)vs (4±3))(P<0.05). And BMI ((26±6) vs (26±4) kg/m2)(P<0.05), WC ((84±11) vs (82±12) cm) (P<0.05), FPG ((8±4) vs (6±4)mmol/L)(P<0.05), FPI ((17±4) vs (16±4)μU/ml)(P<0.05)and HbA1C((7.4±0.9)% vs(7.0±1.2)%)(P<0.05)decreased statistically significant only in 15-20 ng/ml group. Multivariate regression analysis showed that HOMA-IR was a significant independent risk factor for 25 (OH) D (OR=13, 95%CI=4-39, P<0.05).


Conclusion
There are significant improvements in BMI, WC, FPG, FPI, HbA1C and HOMA-IR after supplementation.Thus vitamin D supplementation may reduce insulin resistance in T2DM.


Key words: 
Type 2 diabetes; Insulin resistance; Vitamin D

Effects of vitamin D supplementation on insulin resistance in patients with type 2 diabetes mellitus

BACKGROUND: The effects of a high protein diet on insulin secretion and glucose metabolism have been quite controversial. The aim of this study was to evaluate the effects of long-term isocaloric high animal protein intake on insulin secretion in diet-induced obese rats.



RESULTS: After the experimental period (24 weeks), the high-fat diet-induced obese rats that were fed isocaloric high-protein diets (HP) had lower body weight gain (P < 0.01) and lower visceral fat (P < 0.05) than normal protein (NP) rats. Fasting plasma glucagon-like peptide-1 (GLP-1) was also reduced significantly (P < 0.05), as well as serum insulin levels at 5 min and 10 min by intravenous insulin releasing test. In addition, insulin mRNA and pancreatic duodenal homeodomain-1 (PDX-1), GLP-1 protein expression were both markedly lower in HP rats (P < 0.05), while PDX-1 mRNA in HP rats had no difference from NP rats.



CONCLUSION: These results suggest that long-term isocaloric high animal protein intake reduces the acute insulin response in obese rats and the decrease of insulin is associated with both reduced weight gain and inhibition of PDX-1 expression. GLP-1 might be a negative feedback for the balance of energy metabolism secondary to changes of body weight and visceral fat. Copyright © 2012 Society of Chemical Industry

Haiyan Chen

Papers

MiR-490-3p modulates the proliferation of vascular smooth muscle cells induced by ox-LDL through targeting PAPP-A

Effects of vitamin D supplementation on insulin resistance in patients with type 2 diabetes mellitus

Long-term high animal protein diet reduces body weight gain and insulin secretion in diet-induced obese rats