Aims The aim of the present paper was to provide an up-to-date view on epidemiology and risk factors of heart failure (HF) development after myocardial infarction. Methods and results Based on literature review, several clinical risk factors and biochemical, genetic, and imaging biomarkers were identified to predict the risk of HF development after myocardial infarction. Conclusions Heart failure is still a frequent complication of myocardial infarction. Timely identification of subjects at risk for HF development using a multimodality approach, and early initiation of guideline-directed HF therapy in these patients, can decrease the HF burden.

Heart failure after myocardial infarction: incidence and predictors.

Atherosclerosis, driven by chronic inflammation of the arteries and lipid accumulation on the blood vessel wall, underpins many cardiovascular diseases with high mortality rates globally, such as stroke and ischemic heart disease. Engineered bio-nanomaterials are now under active investigation as carriers of therapeutic and/or imaging agents to atherosclerotic plaques. This Review summarizes the latest bio-nanomaterial-based strategies for managing atherosclerosis published over the past five years, a period marked by a rapid surge in preclinical applications of bio-nanomaterials for imaging and/or treating atherosclerosis. To start, the biomarkers exploited by emerging bio-nanomaterials for targeting various components of atherosclerotic plaques are outlined. In addition, recent efforts to rationally design and screen for bio-nanomaterials with the optimal physicochemical properties for targeting plaques are presented. Moreover, the latest preclinical applications of bio-nanomaterials as carriers of imaging, therapeutic, or theranostic agents to atherosclerotic plaques are discussed. Finally, a mechanistic understanding of the interactions between bio-nanomaterials and the plaque ("athero-nano" interactions) is suggested, the opportunities and challenges in the clinical translation of bio-nanomaterials for managing atherosclerosis are discussed, and recent clinical trials for atherosclerotic nanomedicines are introduced.

Recent Advances in Managing Atherosclerosis via Nanomedicine.

Macrophages are highly heterogeneous and plastic cells. They were shown to play a critical role in all stages of atherogenesis, from the initiation to the necrotic core formation and plaque rupture. Lesional macrophages primarily derive from blood monocyte, but local macrophage proliferation as well as differentiation from smooth muscle cells have also been described. Within atherosclerotic plaques, macrophages rapidly respond to changes in the microenvironment, shifting between pro- (M1) or anti-inflammatory (M2) functional phenotypes. Furthermore, different stimuli have been associated with differentiation of newly discovered M2 subtypes: IL-4/IL-13 (M2a), immune-complex (M2b), IL-10/glucocorticoids (M2c), and adenosine receptor agonist (M2d). More recently, additional intraplaque macrophage phenotypes were also recognized in response to CXCL4 (M4), oxidized phospholipids (Mox), haemoglobin/haptoglobin complexes (HA-mac/M(Hb)), and heme (Mhem). Such macrophage polarization was described as a progression among multiple phenotypes, which reflect the activity of different transcriptional factors and the cross-talk between intracellular signalling. Finally, the distribution of macrophage subsets within different plaque areas was markedly associated with cardiovascular (CV) vulnerability. The aim of this review is to update the current knowledge on the role of macrophage subsets in atherogenesis. In addition, the molecular mechanisms underlying macrophage phenotypic shift will be summarised and discussed. Finally, the role of intraplaque macrophages as predictors of CV events and the therapeutic potential of these cells will be discussed.

Pathophysiological relevance of macrophage subsets in atherogenesis.

The endothelial cells (ECs) forming the inner wall of every blood vessel are constantly exposed to the mechanical forces generated by blood flow. The EC responses to these hemodynamic forces play a critical role in the homeostasis of the circulatory system. A variety of mechanosensors and transducers, locating on the EC surface, intra- and trans-EC membrane, and within the EC cytoskeleton, have thus been identified to ensure proper functions of ECs. Among them, the most recent candidate is the endothelial surface glycocalyx (ESG), which is a matrix-like thin layer covering the luminal surface of the EC. It consists of various proteoglycans, glycosaminoglycans, and plasma proteins and is close to other prominent EC mechanosensors and transducers. This chapter summarizes the ESG composition, thickness, and structure observed by different labeling and visualization techniques and in different types of vessels. It also presents the literature in determining the ESG mechanical properties by atomic force microscopy and optical tweezers. The molecular mechanisms by which the ESG plays the role in EC mechanosensing and transduction are described as well as the ESG remodeling by shear stress, the actin cytoskeleton, the membrane rafts, the angiogenic factors, and the sphingosine-1-phosphate.

The Role of Endothelial Surface Glycocalyx in Mechanosensing and Transduction.

Atherosclerosis is the root of approximately one-third of global mortalities. Nanotechnology exhibits splendid prospects to combat atherosclerosis at the molecular level by engineering smart nanoagents with versatile functionalizations. Significant advances in nanoengineering enable nanoagents to autonomously navigate in the bloodstream, escape from biological barriers, and assemble with their nanocohort at the targeted lesion. The assembly of nanoagents with endogenous and exogenous stimuli breaks down their shells, facilitates intracellular delivery, releases their cargo to kill the corrupt cells, and gives imaging reports. All these improvements pave the way toward personalized medicine for atherosclerosis. This review systematically summarizes the recent advances in stimuli-responsive nanoagents for atherosclerosis management and its progress in clinical trials.

Atherosclerosis Treatment with Stimuli-Responsive Nanoagents: Recent Advances and Future Perspectives

The neutrophil to lymphocyte ratio (NLR) is an indicator of systemic inflammation and a prognostic marker in patients with acute coronary syndrome (ACS). This study aims to investigate the value of NLR to predict the in-hospital and long-term prognosis in patients with ST segment elevation myocardial infarction (STEMI) after percutaneous coronary intervention (PCI) by meta-analysis. The studies related to the prognosis of NLR and STEMI patients published in the Pubmed, Embase, and Ovid databases before June 2017 were retrieved. The relevant data were extracted. Review Manager Version 5.3 was used for meta-analysis. A total of 14 studies of 10,245 patients with STEMI after PCI were included. A significant difference was observed for mortality (P < 0.001; relative risk (RR) 3.32; 95% confidence interval (CI) 2.45–4.49), hospital cardiac mortality(P < 0.001; RR 3.22; 95% CI 2.25–4.60), all mortality (P < 0.001; RR 3.23; 95% CI 2.28–4.57), major adverse cardiovascular events (MACE) (P < 0.001; RR 2.00; 95% CI 1.62–2.46), in-stent thrombosis (P < 0.001; RR 2.72 95% CI 1.66–4.44), nonfatal myocardial infarction(MI) (P < 0.001; RR 1.93; 95%CI 1.43–2.61), angina (P = 0.007; RR 1.67; 95%CI 1.15–2.41), advanced heart failure (AHF) (P < 0.001; RR 1.81; 95% CI 1.48–2.21), arrhythmia (P = 0.002; RR 1.38; 95% CI 1.13–1.69), no reflow (P < 0.001; RR 2.28; 95% CI 1.46–3.57), long-term all mortality (P < 0.001; RR 3.82; 95% CI 2.94–4.96), cardiac mortality (P = 0.004; RR 3.02; 95% CI 1.41–6.45), MACE (P < 0.001; RR 2.49; 95% CI 1.47–4.23), and nonfatal MI (P = 0.46; RR 1.32; 95% CI 0.63–2.75). Meta-analysis shows that NLR is a predictor of hospitalization and long-term prognosis in patients with STEMI after PCI, but requires further confirmation by large randomized clinical trials.

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Predictive value of neutrophil to lymphocyte ratio in patients with acute ST segment elevation myocardial infarction after percutaneous coronary intervention: a meta-analysis

Background
Rupture of an atherosclerotic plaque is the primary cause of acute cardiovascular and cerebrovascular syndromes. Early and non-invasive detection of vulnerable atherosclerotic plaques (VP) would be significant in preventing some aspects of these syndromes. As a new contrast agent, dimercaptosuccinic acid (DMSA) modified ultra-small super paramagnetic iron oxide (USPIO) was synthesized and used to identify VP and rupture plaque by magnetic resonance imaging (MRI).

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Identifying Vulnerable Atherosclerotic Plaque in Rabbits Using DMSA-USPIO Enhanced Magnetic Resonance Imaging to Investigate the Effect of Atorvastatin

Ultrasmall superparamagnetic iron oxide (USPIO) can identify atherosclerotic vulnerable plaque and atorvastatin can stabilize vulnerable plaque by inhibiting the inflammatory response. Using balloon injury in rabbit abdominal aortic endothelial cells and p53 gene transfecting the local plaque, we established an atherosclerotic vulnerable plaque model. In the treatment group, animals were treated with atorvastatin for 8 weeks. At the end of week 16, the animals in each group underwent medication trigger. USPIO-enhanced MRI was utilized to detect vulnerable plaque formation and the transformation of stable plaque in the treatment group. Pathological and serological studies were conducted in animal sera and tissues. The images from the USPIO-enhanced MRI, and the vulnerable plaque showed low signal, especially on T2*-weighted sequences (T2*WI). Plaque signal strength reached a negative enhancement peak at 96 h. Compared with the other groups, lipids, cell adhesion molecule-1 and vascular cell adhesion molecule-1 levels were significantly lower (P<0.05) in the treatment group. In conclusion, USPIO-enhanced MRI can identify vulnerable plaque formation by deposition in macrophages, while atorvastatin is able to inhibit the progression of atherosclerosis and promote plaque transformation to the stable form.

/pdf/experimental-study-of-uspio-enhanced-mri-in-the-detection-of-4usp014o58.pdf

Experimental study of USPIO-enhanced MRI in the detection of atherosclerotic plaque and the intervention of atorvastatin

This study's goal was to assess the diagnostic value of the USPIO-(ultra-small superparamagnetic iron oxide) enhanced magnetic resonance imaging (MRI) in detection of vulnerable atherosclerotic plaques in abdominal aorta in experimental atherosclerosis. Thirty New Zealand rabbits were randomly divided into two groups, Group A and Group B. Each group comprised 15 animals which were fed with high cholesterol diet for 8 weeks and then subjected to balloon-induced endothelial injury of the abdominal aorta. After another 8 weeks, animals in Group B received adenovirus carrying p53 gene that was injected through a catheter into the aortic segments rich in plaques. Two weeks later, all rabbits were challenged with the injection of Chinese Russell's viper venom and histamine. Pre-contrast images and USPIO-enhanced MRI images were obtained after pharmacological triggering with injection of USPIO for 5 days. Blood specimens were taken for biochemical and serological tests at 0 and 18 weeks. Abdominal aorta was histologically studied. The levels of serum ICAM-1 and VCAM-1 were quantified by ELISA. Vulnerable plaques appeared as a local hypo-intense signal on the USPIO-enhanced MRI, especially on T2*-weighted sequences. The signal strength of plaques reached the peak at 96 h. Lipid levels were significantly (p < 0.05) higher in both Group A and B compared with the levels before the high cholesterol diet. The ICAM-1 and VCAM-1 levels were significantly (p < 0.05) higher in Group B compared with Group A. The USPIO-enhanced MRI efficiently identifies vulnerable plaques due to accumulation of USPIO within macrophages in abdominal aorta plaques.

Detection of Vulnerable Atherosclerotic Plaques in Experimental Atherosclerosis with the USPIO-Enhanced MRI

Introduction The pathophysiological mechanisms linking the overweight and prothrombotic state of non-valvular atrial fibrillation (NVAF) are incompletely understood. Our objective was to evaluate the effect of platelet CD36 on the risk of stroke associated with overweight in NVAF patients. Methods A cross-sectional study enrolled 182 subjects with NVAF in two groups: normal weight (18.5 < body mass index(BMI) < 25.0 kg/m2) and overweight (BMI ≥ 25.0 kg/m2). Clinical data, medical history, vital signs, transthoracic echocardiography parameters, and medication were recorded. Biochemical characteristics including blood glucose and serum lipid were analyzed in the Laboratory. Results The expression of platelet CD36 and integrin αIIbβ3 was detected by flow cytometry. Among the 182 patients with NVAF, 68 (37.36%) were classified as normal weight, 114 (62.64%) as overweight. With an increase in BMI, waist-hip ratio, cholesterol, triglycerides, left atrium diameters, and the ratio of mitral inflow E velocity to myocardial e' velocity in the mitral annulus (E/e') increased significantly (P < 0.05). The mean fluorescent intensity of platelet CD36 increased significantly in overweight patients (P < 0.01), in line with platelet activation biomarkers (platelet integrin αIIbβ3). Platelet CD36 was positively correlated with BMI and platelet integrin αIIbβ3, respectively (P < 0.05). Additionally, platelet CD36 and BMI were independent risk factors for platelet activation in patients with NVAF. Conclusions Platelet CD36 is speculated to mediate the complex crosstalk between overweight and platelet hyperactivity, leading to the prothrombotic state in overweight patients with NVAF. Platelet CD36 could be a potential target for preventing the prothrombotic state in overweight patients with NVAF.

Lei Gong

Papers

Predictive value of neutrophil to lymphocyte ratio in patients with acute ST segment elevation myocardial infarction after percutaneous coronary intervention: a meta-analysis

Identifying Vulnerable Atherosclerotic Plaque in Rabbits Using DMSA-USPIO Enhanced Magnetic Resonance Imaging to Investigate the Effect of Atorvastatin

Experimental study of USPIO-enhanced MRI in the detection of atherosclerotic plaque and the intervention of atorvastatin

Detection of Vulnerable Atherosclerotic Plaques in Experimental Atherosclerosis with the USPIO-Enhanced MRI

Platelet CD36 links overweight and a prothrombotic phenotype in patients with non-valvular atrial fibrillation