Neutrophil extracellular traps (NETs) have recently emerged as a newly recognized contributor to venous and arterial thrombosis. These strands of DNA extruded by activated or dying neutrophils, decorated with various protein mediators, become solid-state reactors that can localize at the critical interface of blood with the intimal surface of diseased arteries and propagate and amplify the regional injury. NETs thus furnish a previously unsuspected link between inflammation, innate immunity, thrombosis, oxidative stress, and cardiovascular diseases. In response to disease-relevant stimuli, neutrophils undergo a specialized series of reactions that culminate in NET formation. DNA derived from either nuclei or mitochondria can contribute to NET formation. The DNA liberated from neutrophils forms a reticular mesh that resembles morphologically a net, rendering the acronym NETs particularly appropriate. The DNA backbone of NETs not only presents intrinsic neutrophil proteins (eg, MPO [myeloperoxidase] and various proteinases) but can gather other proteins found in blood (eg, tissue factor procoagulant). This review presents current concepts of neutrophil biology, the triggers to and mechanisms of NET formation, and the contribution of NETs to atherosclerosis and to thrombosis. We consider the use of markers of NETs in clinical studies. We aim here to integrate critically the experimental literature with the growing body of clinical information regarding NETs.Adaptive as well as innate immune responses contribute to the development of atherosclerosis. Studies performed in experimental animals have revealed that some of these immune responses are protective while others contribute to the progression of disease. These observations suggest that it may be possible to develop novel therapies for cardiovascular disease by selectively modulating such atheroprotective and proatherogenic immunity. Recent advances in cancer treatment using immune check inhibitors and CAR (chimeric antigen receptor) T-cell therapy serve as excellent examples of the possibilities of targeting the immune system to combat disease. LDL (low-density lipoprotein) that has accumulated in the artery wall is a key autoantigen in atherosclerosis, and activation of antigen-specific T helper 1-type T cells is thought to fuel plaque inflammation. Studies aiming to prove this concept by immunizing experimental animals with oxidized LDL particles unexpectedly resulted in activation of atheroprotective immunity involving regulatory T cells. This prompted several research groups to try to develop vaccines against atherosclerosis.  https://www.selleckchem.com/products/mivebresib-abbv-075.html  In this review, we will discuss the experimental and clinical data supporting the possibility of developing immune-based therapies for lowering cardiovascular risk. We will also summarize ongoing clinical studies and discuss the challenges associated with developing an effective and safe atherosclerosis vaccine.Atherosclerosis is a chronic inflammatory vascular disease and the predominant cause of heart attack and ischemic stroke. Despite the well-known sexual dimorphism in the incidence and complications of atherosclerosis, there are relatively limited data in the clinical and preclinical literature to rigorously address mechanisms underlying sex as a biological variable in atherosclerosis. In multiple histological and imaging studies, overall plaque burden and markers of inflammation appear to be greater in men than women and are predictive of cardiovascular events. However, while younger women are relatively protected from cardiovascular disease, by the seventh decade, the incidence of myocardial infarction in women ultimately surpasses that of men, suggesting an interaction between sex and age. Most preclinical studies in animal atherosclerosis models do not examine both sexes, and even in those that do, well-powered direct statistical comparisons for sex as an independent variable remain rare. This article revitill the leading cause of death of men and women worldwide.The term phenotype is so commonly used that we often assume that we each mean the same thing. The general definition, the set of observable characteristics of an individual resulting from the interaction of their genotype with the environment, is often left to the eye of the beholder. Whether applied to the multiple levels of biological phenomena or the intact human being, our ability to characterize, classify, and analyze phenotype has been limited by measurement deficits, computing limitations, and a culture that avoids the generalizable. With the advent of modern technology, there is the potential for a revolution in phenotyping, which incorporates old and new in structured ways to dramatically advance basic understanding of biology and behavior and to lead to major improvements in clinical care and public health. This revolution in how we think about phenotypes will require a radical change in the scale at which biomedicine operates with significant changes in the unit of action, which will have far-reaching implications for how care, translation, and discovery are implemented.Epigenetic mechanisms involve the placing (writing) or removal (erasing) of histone modifications that allow heterochromatin to transition to the open, activated euchromatin state necessary for transcription. A third, less studied epigenetic pathway involves the reading of these specific histone marks once placed. The BETs (bromodomain and extraterminal-containing protein family), which includes BRD2, BRD3, and BRD4 and the testis-restricted BRDT, are epigenetic reader proteins that bind to specific acetylated lysine residues on histone tails where they facilitate the assembly of transcription complexes including transcription factors and transcriptional machinery like RNA Polymerase II. As reviewed here, considerable recent data establishes BETs as novel determinants of induced transcriptional programs in vascular cells, like endothelial cells and vascular smooth muscle cells, cardiac myocytes and inflammatory cells, like monocyte/macrophages, cellular settings where these epigenetic reader proteins couple proximal stimuli to chromatin, acting at super-enhancer regulatory regions to direct gene expression.