Weak UVB Irradiation Promotes Macrophage M2 Polarization and Stabilizes Atherosclerosis.

Atherosclerosis (AS) is a chronic cardiovascular disease endangering human health and is one of the most common causes of myocardial infarction and stroke. Macrophage polarization plays a vital role in regulating plaque stability. As an important component of sunlight, ultraviolet B (UVB) has been proven to promote vitamin D and nitric oxide synthesis. This research used an AS model in ApoE-/- mice to study the effects of UVB on macrophage polarization and atherosclerotic plaque stability. In vitro, UVB irradiation increased arginase-I (Arg-I, M2 macrophage) and macrophage mannose receptor (CD206) expression, while the expression of inducible nitric oxide synthase (iNOS) (M1 macrophage) and CD86 was decreased. UVB promoted Akt phosphorylation in vitro. In vivo, UVB irradiation promoted the stabilization of atherosclerotic lesion plaques, while the phenotype of M2 macrophages increased. Our research provides new evidence for UVB in preventing and treating atherosclerosis.

Correction to: AVE0991, a nonpeptide angiotensin-(1-7) mimic, inhibits angiotensin II-induced abdominal aortic aneurysm formation in apolipoprotein E knockout mice.

The corrected Figure 7 image is presented in this paper.

AVE0991, a nonpeptide angiotensin-(1-7) mimic, inhibits angiotensin II-induced abdominal aortic aneurysm formation in apolipoprotein E knockout mice.

AVE0991, a nonpeptide angiotensin-(1-7) mimic, has similar protective effects for cardiovascular system to Ang-(1-7). In this article, we aimed to explore the effects of AVE0991 and Ang-(1-7) on abdominal aortic aneurysm (AAA) induced by Ang II in apolipoprotein E knockout mice. The mice AAA model was established by Ang II infusion, and then mice received different treatment with saline, Ang II (1.44 mg/kg/day), different dose AVE0991 (0.58 or 1.16 µmol/kg/day), or Ang-(1-7) (400 ng/kg/min). The incidence of AAA was 76%, 48%, 28%, and 24% in the vehicle, the low-dose AVE0991, high-dose AVE0991, and the Ang-(1-7) group, respectively. In comparison with control group, AVE0991 and Ang-(1-7) treatment significantly increased smooth muscle cells and decreased macrophage accumulation, the expression levels of monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor α (TNF-α), and the expression and activity of metalloproteinases 2 and 9 in mice AAA model or in human smooth muscle cells (hVSMCs). The therapeutic effects may be contributed to reduction of oxidative stress and downregulation of P38 and ERK1/2 signal pathways via Mas receptor activation, whereas the positive impacts were reversed by co-administration with the Mas antagonist A779 (400 ng/kg/min) and AVE0991 in Ang II-infused mice or in hVSMCs. Therefore, AVE0991 and Ang-(1-7) might be novel and promising interventions in the prevention and treatment of AAA. KEY MESSAGES: • AVE0991 dose-dependently inhibited Ang II-induced AAA formation in Apoe-/- mice. • Ang-(1-7) played the same protective role as high-dose AVE0991. • Inhibition of Mas receptor with A779 could reverse the protective effect of AVE0991. • The therapeutic effects may be contributed to reduction of oxidative stress and downregulation of P38 and ERK1/2 signal pathways via Mas receptor activation.

Period 2-Induced Activation of Autophagy Improves Cardiac Remodeling After Myocardial Infarction.

Accumulating evidence indicates that the onset of myocardial infarction (MI) shows obvious circadian rhythmicity. Clinical studies have shown that MIs that occur in the early morning have a poor prognosis, but the mechanisms involved are still unknown. In this study, we showed that the expression level of Period 2 (per2) in the heart of mice is lower in the early morning than at noon and that increasing the expression of per2 in H9C2 cells and rat cardiomyocytes increases autophagy levels. Further studies indicated that overexpression of per2 after an MI improved cardiac function by increasing autophagy. In summary, this study has shown that the circadian clock protein, per2, may be a regulator of MI.

Angiotensin-converting enzyme 2 overexpression protects against doxorubicin-induced cardiomyopathy by multiple mechanisms in rats.

Angiotensin-converting enzyme 2 (ACE2) is considered a potential therapeutic target of the renin-angiotensin system (RAS) for the treatment of cardiovascular diseases. We aimed to explore the effects of ACE2 overexpression on doxorubicin-induced cardiomyopathy in rats. Rats were randomly divided into treatment and control groups. The rats of treatment group were injected intraperitoneally with 6 doses of doxorubicin (2.5 mg/kg) within a period of two weeks. Two weeks after the initial injection of doxorubicin, these rats were randomly divided into Mock, Ad-EGFP, Ad-ACE2, and Cilazapril groups. The rats of Ad-EGFP and Ad-ACE2 groups received intramyocardial injection of Ad-EGFP and Ad-ACE2, respectively. The rats of Cilazapril group received cilazapril (10 mg/kg/day) via intragastric intubation. Apoptosis, inflammation, oxidative stress, cardiac function, the extent of myocardial fibrosis, and levels of ACE2, ACE, angiotensin II (AngII), and angiotensin (1-7) were evaluated. Four weeks after ACE2 gene transfer, the Ad-ACE2 group showed not only reduced apoptosis, inflammatory response, oxidative stress, left ventricular (LV) volume, extent of myocardial fibrosis and mortality of rats, but also increased LV ejection fraction and ACE2 expression level compared with the Mock and Ad-EGFP groups. ACE2 overexpression was superior to cilazapril in improving doxorubicin-induced cardiomyopathy. The putative mechanisms may involve activation of the AMPK and PI3K-AKT pathways, inhibition of the ERK pathway, decrease of TGF-ß1 expression, and interactions of shifting RAS components, such as decreased myocardium AngII levels, increased myocardium Ang (1-7) levels, and reduced ACE expression. Thus, ACE2 may be a novel therapeutic approach to prevent and treat doxorubicin-induced cardiomyopathy.

T cell immunoglobulin and mucin domain-containing molecule 3 on CD14+ monocytes serves as a novel biological marker for diabetes duration in type 2 diabetes mellitus.

AIMS/INTRODUCTION: Type 2 diabetes is a worldwide disease that is associated with increased rates of obesity and reduced physical activity. Obesity-associated insulin resistance in type 2 diabetes is a disorder in the balance between pro-inflammatory and anti-inflammatory signals. T cell immunoglobulin and mucin domain-containing molecule 3 (Tim-3) has been reported as an important regulatory inflammation molecule, and plays a pivotal role in several inflammation-related diseases. MATERIALS AND METHODS: Peripheral blood mononuclear cells were obtained from type 2 diabetes patients (n = 31) and healthy donors (n = 18), and Tim-3 expression on peripheral blood mononuclear cells was evaluated by flow cytometry. RESULTS: We showed the downregulated expression of Tim-3 on CD14+ monocytes from type 2 diabetes patients. In addition, the upregulated expression of Tim-3 on peripheral CD4+ T cells and CD8+ T cells was observed in the present study. The correlation analysis between Tim-3 expression on CD14+ monocytes and diabetes duration showed the longer diabetes duration time, the lower Tim-3 expression on CD14 monocytes. CONCLUSIONS: The present results suggest that Tim-3 might participate in the progression of type 2 diabetes by its negative regulation on these immune cells, and Tim-3 on CD14+ monocytes serves as a novel biological marker for diabetes duration in type 2 diabetes patients.