Association of Soluble Suppression of Tumorigenesis-2 (ST2) with Endothelial Function in Patients with Ischemic Heart Failure.

Soluble suppression of tumorigenesis-2 (sST2) has been introduced as a marker associated with heart failure (HF) pathophysiology and status. Endothelial dysfunction is a component underlying HF pathophysiology. Therefore, we examined the association of arterial wall properties with sST2 levels in patients with HF of ischemic etiology. We enrolled 143 patients with stable HF of ischemic etiology and reduced left ventricular ejection fraction (LVEF) and 77 control subjects. Flow-mediated dilation (FMD) was used to evaluate endothelial function and pulse wave velocity (PWV) to assess arterial stiffness. Although there was no significant difference in baseline demographic characteristics, levels of sST2 were increased in HF compared to the control (15.8 (11.0, 21.8) ng/mL vs. 12.5 (10.4, 16.3) ng/mL; p < 0.001). In the HF group, there was a positive correlation of sST2 levels with age (rho = 0.22; p = 0.007) while there was no association of LVEF with sST2 (rho = -0.119; p = 0.17) nor with PWV (rho = 0.1; p = 0.23). Interestingly, sST2 was increased in NYHA III [20.0 (12.3, 25.7) ng/mL] compared to patients with NYHA II (15.0 (10.4, 18.2) ng/mL; p = 0.003) and inversely associated with FMD (rho = -0.44; p < 0.001) even after adjustment for possible confounders. In patients with chronic HF of ischemic etiology, sST2 levels are increased and are associated with functional capacity. There is an inverse association between FMD and sST2 levels, highlighting the interplay between the dysfunctional endothelium and HF pathophysiologic mechanisms.

Differential Expression of microRNAs in Acute and Chronic Heart Failure.

BACKGROUND: MicroRNAs modify protein expression at the post-transcriptional level, and their circulating levels may help identify the underlying molecular pathways. OBJECTIVE: The purpose of this study was to assess the differential expression of microRNAs related to myocardial cell energy substrate, autophagy, and ischaemia in chronic and acute heart failure (HF). METHODS: In this case-control study, we studied 19 patients with acute HF (AHF) and 19 patients with chronic HF (CHF). Basic demographic and clinical characteristics were collected from the patients upon arrival, at 48 hours, and at 120 hours. Blood samples for microRNAs measurements (miR-22, -92a, and -499), B-type natriuretic peptide (BNP), C reactive protein, and high sensitivity cardiac troponin I, were collected at all study points. In this study, we included subjects with a left ventricular ejection fraction of <40%. RESULTS: At baseline, circulating miR-22 levels were 1.9-fold higher (p<0.001), miR-92a levels were 1.25-fold higher (p=0.003), and miR-499 were 5-times lower (p<0.001) in AHF compared to CHF. Interestingly, circulating miR-499 was found to be associated with BNP levels (r=0.47, p=0.01). At follow-up, there was a stepwise increase in the levels of all three examined microRNAs (miR-22, p=0.001, miR-92a, p=0.001, and miR-499, p<0.001) for AHF but not for CHF subjects. CONCLUSION: MicroRNAs -22, -92a, and -499 are differentially expressed in chronic and acute HF subjects. MicroRNA signatures are also differentially expressed up to the discharge of the patients. These findings may have important implications for diagnosis, progression, and treatment of patients with chronic and acute heart failure.

MicroRNAs in the Management of Heart Failure.

BACKGROUND: In recent years much research has been devoted to the deployment of biomarkers in the field of heart failure. OBJECTIVES: To study the potential of post-transcriptional regulation by microRNAs on the diagnosis, management and therapy of heart failure. METHODS: Literature search focuses on the role of microRNAs in heart failure. RESULTS: MicroRNAs are expressed and regulated in the course of the pathological manifestations of heart failure (HF). This wide and uncharted area of genetic imprints consisting of small non-coding RNA molecule is upregulated and released into the bloodstream from organs under certain conditions and or stress. The use of genetically based strategies for the management of HF has gained great interest in the field of biomedical science because they can be used as biomarkers providing information regarding cardiac status and function. They also appear as promising tools with therapeutic potential because of their ability to induce changes at the cellular level without creating alterations in the gene sequence. In addition, with the advances in genomic sequencing, quantification and synthesis in technologies of microRNAs identification as well as the growing knowledge of the biology of miRNAs and their involvement in HF, it is expected to favorably affect the prognosis of HF patients. CONCLUSION: MicroRNAs are involved in the regulation of multibiological processes involved in the progress of heart failure. More studies are needed to achieve a clinical valuable implementation of microRNAs in the management of HF.

Basic Mechanisms in Atherosclerosis: The Role of Calcium.

In the beginning, atherosclerosis was considered to be the result of passive lipid accumulation in the vascular walls. After tremendous technological advancements in research, we are now able to almost admire the complexity of the atherosclerotic process. Atherosclerosis is a chronicinflammatory condition that begins with the formation of calcified plaque, influenced by a number of different factors inside the vascular wall in large and mid-sized arteries. Calcium mineralization of the lumen in the atherosclerotic artery promotes and solidifies plaque formation causing narrowing of the vessel. Soft tissue calcification associated with tissue denegation or necrosis is a passive precipitation event. The process of atherogenesis is mainly driven by CD4+ T cells, CD40L, macrophages, foam cells with elevated transcription of many matrix metalloproteinases, osteoblasts, cytokines, selectins, myeloperoxidases, vascular adhesion molecules (VCAM), and smooth muscle cells. Our knowledge in the genesis of atherosclerosis has changed dramatically in the last few years. New imaging techniques such as intravascular ultrasound or IVUS have made possible to investigate atherosclerosis in early stages. Arterial calcification emerges from two different types, the medial-elastin dependent and the intimal, both of which are directly related to atherosclerosis due to osteoblast differentiation of vascular smooth muscle cells. The deposition of minerals in the form of calcium (Ca(2+)) initially emerges from the inorganing mineral octacalcium phosphate [Ca8H2(PO4)6.5H2O] to the form of Hydroxylapatite [Ca10(PO4)6(OH)2]. This review is devoted to broaden the understanding regarding atherosclerosis and the central role of calcium in the development of the condition.

The Role of Endothelial Dysfunction in Aortic Aneurysms.

Abdominal aortic aneurysm is a vascular disease which, despite the fact that it shares common risk factors with atherosclerosis, develops in parallel but as a partly independent process, through different pathogenic mechanisms. The pathogenic mechanisms involve metalloproteinase and collagenase activation, median and adventitial degradation, elastin lysis, vascular smooth cells transformation and apoptosis, collagen production and lysis imbalance combined with excessive inflammatory infiltration. Endothelial cells respond to a number of stimulating factors, including smoking, hypertension and AT1 receptor stimulation and non-uniform distribution of wall stress. Their ability to produce NO is crucial in order to adapt. Endothelial cells contribute to AAA development due to increased oxidative stress which is partly mediated by impaired NO bioavailability due to endothelial dysfunction and NADPH oxidase overexpression. In addition, they express several molecules among which adherence molecules, selectins, endothelin-1, regulating inflammatory infiltration and oxidative stress. Inflammatory cells consist of monocytes, polymorphonuclear neutrophils and lymphocytes and they are involved in the degrading process in the aortic wall by secreting proteolytic enzymes or by releasing interleukins which mediate the inflammation response. Endothelial dysfunction and arterial stiffness reflect on indices like FMD, carotid-femoral PWV and augmentation index, sometimes with controversial results. At present, surgical treatment is the only option provided in patients with large AAA, in particular. Focusing on the emerging role of endothelial cells in AAA pathology may contribute in creating new therapeutic options in a disease which has not yet a well-accepted, implemented pharmaceutical treatment.