Significance of plasma free fatty acid level for assessing and diagnosing acute myocardial infarction.

Aim: To clarify the diagnostic value of the circulating free fatty acid (FFA) level for acute myocardial infarction (AMI) in coronary heart disease patients. Methods & results: A total of 1776 patients were screened by coronary angiography from October 2014 to February 2016. The plasma FFA level was significantly higher in coronary heart disease patients with lesions in three or more vessels than those with lesions in one or two vessels. Moreover, an elevated FFA level was identified as an independent risk factor for AMI on multivariate regression analysis and shown to be a sensitive and specific indicator for AMI diagnosis by receiver operating characteristic curve analysis. Conclusion: An elevated FFA level is an independent risk factor and independent diagnostic marker for AMI.

miR-93-5p-Containing Exosomes Treatment Attenuates Acute Myocardial Infarction-Induced Myocardial Damage.

Adipose-derived stromal cells (ADSCs) have been considered as an attractive therapeutic tool. Accumulating evidence indicates that the healing effects of ADSCs are mainly related to paracrine action rather than transdifferentiation. Data show that the expression of miR-93-5p has a cardio-protective effect after acute myocardial infarction (AMI). To identify whether miR-93-5p-encapsulating exosomes that form ADSCs have a better cardio-protective effect, we investigated the inflammatory factors and miR-30d-5p expression in clinical levels. A rat model of AMI and an in vitro model of hypoxic H9c2 cells were established to study the protective mechanism of miR-93-5p in ischemia-induced cardiac injury. The results show that the expression of inflammatory cytokines and miR-93-5p were increased following AMI in both patients and animal models. Moreover, treatment with ADSC-derived miR-93-5p-containing exosomes has a greater protective effect on infarction-induced myocardial damage than simple exosome processing. Furthermore, in vitro experiments confirmed that the expression of miR-93-5p can significantly suppress hypoxia-induced autophagy and inflammatory cytokine expression by targeting Atg7 and Toll-like receptor 4 (TLR4), respectively, and was confirmed with Atg7 or TLR4 overexpression. The results also show that autophagy activation can promote inflammatory cytokine expression indirectly. Taken together, these results suggest that the miR-93-5p-enhanced ADSC-derived exosomes prevent cardiac injury by inhibiting autophagy and the inflammatory response.

miR-146b-5p promotes VSMC proliferation and migration.

Vascular smooth muscle cells (VSMCs) play pivotal roles in the development of vascular diseases. While microRNAs are important in vascular pathologies, a few is known about their functional roles in VSMC phenotypes. We profiled microRNA expression in PDGF-BB treated VSMCs and found microRNA-146b-5p (miR-146b-5p) was upregulated. Inhibition of miR-146b-5p blocked in response to PDGF while reducing VSMC proliferation and migration. These studies implicate miR-146b-5p as necessary for PDGF-induced VSMC phenotype transition. Downstream miR-146b-5p targets modulating VSMC phenotypes will be further identified. Our study will help to understand the role of VSMCs in the pathology of vascular diseases.

Quantitative assessment of the influence of PSMA6 variant (rs1048990) on coronary artery disease risk.

The proteasome system is a proteolytic pathway that regulates the expression of genes involved in inflammation. Recently, an association of a functional sequence variation, -8C/G, in the human proteasome subunit a type 6 gene (PSMA6) with the susceptibility to coronary artery disease (CAD) was reported. After that, several validation studies have been conducted among various ethnic populations, but the results have been inconsistent. To investigate this inconsistency and derive a more precise estimation of the relationship, a meta-analysis of 15,991 cases and 16,784 controls from 10 case-control studies was performed. Potential sources of heterogeneity including ethnicity, sample size and HWE status of study were also assessed. In a combined analysis, the summary per-allele OR for CAD of the -8C/G polymorphism was 1.09 (95 % CI: 1.02-1.16; P = 0.006). In the subgroup analysis by ethnicity, significantly increased risks were found in East Asians for the polymorphism; while no significant associations were found among Caucasians and other ethnic population in all genetic models. When restricted to studies concerning myocardial infarction patients, significant associations were detected in all genetic models. Furthermore, significant difference of PSMA6 mRNA expression was found between genotypes. In conclusion, this meta-analysis suggests that G allele of PSMA6-8C/G polymorphism is a risk factor associated with increased CAD susceptibility, but these associations vary in different ethnic populations.

Intensive-dose atorvastatin regimen halts progression of atherosclerotic plaques in new-onset unstable angina with borderline vulnerable plaque lesions.

To compare the therapeutic effects of intensive versus moderate dosage of atorvastatin regimens in new-onset unstable angina with borderline lesions, 100 patients were randomized to receive either 80 mg/d or 20 mg/d atorvastatin for 9 months. Clinical symptoms, lipid profiles, and coronary stenosis (evaluated by coronary angiography and intravascular ultrasound) were compared to their corresponding baselines within each group and between the 2 groups after 9 months of treatment. The results showed that (1) when compared to their corresponding baselines, both groups exhibited improvement in clinical symptoms, a significant decrease in total cholesterol, triglyceride, low-density lipoprotein cholesterol (LDL-C), and high-sensitivity C-reactive protein (hs-CRP; P < .01) and a significant increase in high-density lipoprotein cholesterol (HDL-C); (2) the improvement in clinical symptoms and the decrease in LDL-C and hs-CRP were significantly greater (P < .01) in the intensive-dose group than in the moderate-dose group; (3) the mean plaque volume did not progress in the intensive-dose group but increased significantly (P < .05) in the moderate-dose group. We conclude that compared to the moderate dose, the intensive-dose regimen significantly improves clinical symptoms, lowers LDL-C and hs-CRP, and halts the progression of borderline atherosclerotic plaques in patients with new-onset unstable angina.

Is asthma related to choroidal neovascularization?

BACKGROUND: Age-related degeneration (AMD) and asthma are both diseases that are related to the activation of the complement system. The association between AMD and asthma has been debated in previous studies. The authors investigated the relationship between AMD and asthma systemically. PRINCIPAL FINDINGS: The epidemiological study showed that asthma was related to choroidal neovascularization (CNV) subtype (OR = 1.721, P = 0.023). However, the meta-analysis showed there was no association between AMD and asthma. In an animal model, we found more fluoresce in leakage of CNV lesions by FA analysis and more angiogenesis by histological analysis in rats with asthma. Western blot demonstrated an elevated level of C3α-chain, C3α'-chain and VEGF. After compstatin was intravitreally injected, CNV leakage decreased according to FA analysis, with the level of C3 and VEGF protein decreasing at the same time. SIGNIFICANCE: This study first investigated the relationship between AMD and asthma systematically, and it was found that asthma could be a risk factor for the development of AMD. The study may provide a better understanding of the disease, which may advance the potential for screening asthma patients in clinical practice.