Diagnostic and prognostic significance of miR-451a in patients with atherosclerosis

Objectives Atherosclerosis (AS) is a chronic inflammatory vascular disease. This study aimed to detect the expression level of miR-451a and investigate the diagnostic and prognostic values of miR-451a for AS patients. Methods The relative expression of miR-451a was assessed by qRT-PCR. Comparison of groups was analyzed with the t-test and chi-squared test. Pearson analysis was used to validate the correlation of miR-451 with CRP and CIMT. The receiver operating characteristic (ROC) curves, K-M analysis, and Cox regression analysis were conducted to explore the roles of miR-451a in diagnosing AS patients and predicting outcomes of AS patients. Results The expression of miR-451a was significantly decreased in the serum of AS patients. The results of Pearson analysis showed the expression of miR-451a was negatively correlated with CRP and CIMT. The data of ROC proposed miR-451a could differentiate AS patients from healthy individuals with high sensitivity and specificity. K-M analysis and Cox regression showed miR-451a might be an independent biomarker of suffering cardiovascular endpoint diseases in AS patients. The expression of miR-451a was obviously inhibited in AS patients with cardiovascular endpoint events. Conclusion Deregulation of miR-451a might be associated with the development of AS. MiR-451a might be used as a promising diagnostic and prognostic biomarker for clinical treatment of AS patients.

FABP4 activates the JAK2/STAT2 pathway via Rap1a in the homocysteine-induced macrophage inflammatory response in ApoE−/− mice atherosclerosis

Atherosclerosis is a chronic inflammatory vascular disease, and inflammation plays a critical role in its formation and progression. Elevated serum homocysteine (Hcy) is an independent risk factor for atherosclerosis. Previous studies have shown that fatty acid binding protein 4 (FABP4) plays an important role in macrophage inflammation and lipid metabolism in atherosclerosis induced by Hcy. However, the underlying molecular mechanism of FABP4 in Hcy-induced macrophage inflammation remains unknown. In this study, we found that FABP4 activated the Janus kinase 2/signal transducer and activator of transcription 2 (JAK2/STAT2) pathway in macrophage inflammation induced by Hcy. Of note, we further observed that ras-related protein Rap-1a (Rap1a) induced the Tyr416 phosphorylation and membrane translocation of non-receptor tyrosine kinase (c-Src) to activate the JAK2/STAT2 pathway. In addition, the suppressor of cytokine signaling 1 (SOCS1)—a transcriptional target of signal transducer and activator of transcription (STATs) inhibited the JAK2/STAT2 pathway and Rap1a expression via a negative feedback loop. In summary, these results demonstrated that FABP4 promotes c-Src phosphorylation and membrane translocation via Rap1a to activate the JAK2/STAT2 pathway, contributing to Hcy-accelerated macrophage inflammation in ApoE−/− mice.

Macrophage-Based Therapies for Atherosclerosis Management

Atherosclerosis (AS), a typical chronic inflammatory vascular disease, is the main pathological basis of ischemic cardio/cerebrovascular disease (CVD). Long-term administration was characterized with low efficacy and serious side effects, while the macrophages with attractive intrinsic homing target have great potential in the efficient and safe management of AS. In this review, we focused on the systematical summary of the macrophage-based therapies in AS management, including macrophage autophagy, polarization, targeted delivery, microenvironment-triggered drug release, and macrophage- or macrophage membrane-based drug carrier. In conclusion, macrophage-based therapies have great promise to effectively manage AS in future research and clinic translation.

Changes in and significance of platelet function and parameters in Kawasaki disease

Kawasaki disease (KD) is a systemic febrile, inflammatory vascular disease of unknown etiology. The coronary artery abnormality (CAA) caused by KD has become the most commonly acquired heart disease in children. Initial treatment of intravenous immunoglobulin (IVIG) can reduce the incidence of CAA. Thrombocytosis is common during the course of KD, but changes in and significances of platelet function and parameters are unclear. In this study, we enrolled 120 patients, including 40 patients with KD, 40 febrile controls, and 40 afebrile controls. The platelet function was assessed using the platelet function analyzer (PFA)-200. Platelet parameters, including platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW), and platelet hematocrit (PCT) were measured. In the febrile period, the PDW and MPV were lower in KD patients (P < 0.05). The platelet function did not change significantly during the febrile period of KD but weakened in the defervescence phase. No significant differences between the CAA and normal groups, and between IVIG resistance and response groups. The diagnostic cutoff value of the PDW level for predicting KD was 10.85 fL with a sensitivity of 55% and a specificity of 77.5% (area under curve (AUC) = 0.690, 95% confidence interval (CI): 0.574–0.806, P < 0.01). Besides, the MPV level was 9.55 fL with sensitivity of 75% and specificity of 70% (AUC = 0.733, 95%CI: 0.620–0.846, P < 0.001). This is the first longitudinal study of platelet function changes in KD patients using PFA-200. Besides, lower PDW and MPV may be available markers for early diagnosis of KD.

Does Type 5 of Takayasu's Arteritis Require Subclassification?

Background Takayasu's arteritis (TA) is an inflammatory vascular disease of the young involving the large elastic arteries resulting in occlusive or ectatic changes, mainly in the aorta and its major branches as well as the pulmonary artery and its branches. Materials and Methods The authors reviewed the TA patients admitted over 2 years in their department and who underwent catheterization. They noted the clinical presentations, two-dimensional (2D) echocardiographic features, and angiogram details of all these patients. Results The study population constituted 24 patients with mean age of 28 years. Out of them, 21 (87.5%) were females. Most of the admitted TA patients presented with claudication complaints (79.2%), 37.5% patients had breathlessness, and 12.5% patients had typical stable angina symptoms. Five patients had 2D echo abnormalities, and rest of the patients had normal echocardiogram. Coronary angiogram (CAG) along with aortogram and selective peripheral arteriograms were performed of all these patients. Left main coronary artery (LMCA) disease was seen in three (12.5%) patients. Case details of two (8.3%) patients with multiple anomalous communications of the coronaries with pulmonary vasculature were described. Conclusion TA patients who came for catheterization were predominantly females, mainly involving the aorta and its main branches. In the authors’ TA series of patients, type 5 presentation was there in five (20.8%) patients (three cases of LMCA + two cases of coronary artery to pulmonary parenchymal fistulas). They propose to subclassify type 5 of TA, as they report coronary artery to pulmonary parenchymal fistulas along with the previous literature.

Immunology of the vessel wall

This chapter provides an overview of the vascular wall and its cells from an immunological point of view, discusses the capacity of vascular cells to promote and regulate immune responses, and outlines interactions between the vasculature and the immune system in health and disease. The role of immune mechanisms in vascular diseases is discussed, with a focus on atherosclerosis, a chronic inflammatory vascular disease.

Thromboangiitis obliterans (Buerger’s disease)

Thromboangiitis obliterans (TAO, Buerger`s disease) is an inflammatory vascular disease affecting small and medium sized arteries and veins. It is characterized by segmental thrombotic occlusions by highly mononuclear cellular thrombi. Its occurrence and re-occurrence is closely related to tobacco use. Immunohistological examinations and the detections of various autoantibodies led to the new paradigm of an immunopathogenesis of TAO. Clinically it is characterized by distal ischemia syndromes in young people and high amputation rates. This article summarizes the disease characteristics, clinical features, and diagnostic and therapeutic approaches and focuses on new therapeutic options, i.e. stem cell derived therapies, immunoadsorption, and the endothelin-receptor-blocking agent bosentan.