Harnessing CRISPR/Cas9 technology in cardiovascular disease

The CRISPR/Cas9 system is a precisely targeted bacterial defense system, used to control invading viruses. This technology has many potential applications including genetic changes in somatic and germ cells and the creation of knockout animals. Compared to other genome editing techniques such as zinc-finger nucleases and transcription activator-like effector nucleases (TALENS), the CRISPR/Cas9 system is much easier and more efficient. Most importantly, the multifunctional capacity of this technology allows simultaneous editing of several genes. The CRISPR/Cas9 system also potentially has the ability to prevent and treat human diseases. The present article addresses some key points related to the use of the CRISPR/Cas9 system as a powerful tool in cardiovascular research and as a new strategy for the treatment of cardiovascular disease (CVD)

Atherosclerosis and immunity: A perspective

Atherosclerosis is an inflammatory and multifaceted disorder resulting from the accumulation of lipid droplets and several types of immune cells, including macrophages, T and B lymphocytes in the arterial walls. A wide variety of macrophage subtypes with different functions is implicated in the development and progression of atherosclerotic lesions. The prevalence of specific macrophage subtypes, which is influenced by cytokines, mediators, and substances composing atherosclerotic lesions, has been suggested to be an appropriate indicator of transition from a stable to an unstable plaque phenotype. Thus, a better understanding of the mechanisms underlying the differentiation of macrophage subpopulations in relation to the plaque phenotype would help to develop novel approaches aiming at slowing-down the progression of atherosclerotic disease by modulating the polarization of these cells. In addition, many arms of the adaptative immune system, which are regulated by different subtypes of T and B lymphocytes, are involved in atherosclerosis progression and there is an increasing effort to identify immune-modulating therapies targeting either T or B cells with a potential anti-atherosclerotic impact. This paper summarizes the pathophysiology of atherosclerotic disease as it relates to the contribution from the immune system, reviewing the crucial role of macrophages, T and B lymphocytes. Keywords: Atherosclerosis,Macrophages, Atherosclerotic ,lesion,Plaque,Immunit

Wnt network: A brief review of pathways and multifunctional components

The Wnt signaling pathway appears to activate intracellular signaling transduction in embryonic development, cell migration, hematopoiesis, and several diseases. Wnt signaling is basically recognized as a canonical beta-catenindependent signaling pathway. However, in recent years, generally three Wnt-mediated pathways have been investigated, which operate independently of beta-catenin and include calcium/calmodulin-dependent kinase II and protein kinase C, planar cell polarity, and a third one recruits hetrotrimeric GTP-binding proteins to stimulate phospholipase C and phosphodiesterase. We provide an overview of the noncanonical Wnt signaling pathway and then will focus on canonical Wnt signaling components, Wnt ligands, agonists, and antagonist. This review will also discuss beta-catenin, both cytoplasmic and nuclear mechanisms, through signaling transduction, and, as a consequence, we have briefly highlighted potential implications of Wnt/beta-catenin in some cancers

The Role of Efferocytosis in Autoimmune Diseases

Apoptosis happens continuously for millions of cells along with the active removal of apoptotic debris in order to maintain tissue homeostasis. In this respect, efferocytosis, i.e., the process of dead cell clearance, is orchestrated through cell exposure of a set of “find me,” “eat me,” and “tolerate me” signals facilitating the engulfment of dying cells through phagocytosis by macrophages and dendritic cells. The clearance of dead cells via phagocytes is of utmost importance to maintain the immune system tolerance to self-antigens. Accordingly, this biological activity prevents the release of autoantigens by dead cells, thus potentially suppressing the undesirable autoreactivity of immune cells and the appearance of inflammatory autoimmune disorders as systemic lupus erythematous and rheumatoid arthritis. In the present study, the apoptosis pathways and their immune regulation were reviewed. Moreover, efferocytosis process and its impairment in association with some autoimmune diseases were discussed. Keywords: apoptosis, efferocytosis, autoimmune disease, phagocytosis, systemic lupus erythematou

The Role of Efferocytosis in Autoimmune Diseases

Apoptosis happens continuously for millions of cells along with the active removal of apoptotic debris in order to maintain tissue homeostasis. In this respect, efferocytosis, i.e., the process of dead cell clearance, is orchestrated through cell exposure of a set of “find me,” “eat me,” and “tolerate me” signals facilitating the engulfment of dying cells through phagocytosis by macrophages and dendritic cells. The clearance of dead cells via phagocytes is of utmost importance to maintain the immune system tolerance to self-antigens. Accordingly, this biological activity prevents the release of autoantigens by dead cells, thus potentially suppressing the undesirable autoreactivity of immune cells and the appearance of inflammatory autoimmune disorders as systemic lupus erythematous and rheumatoid arthritis. In the present study, the apoptosis pathways and their immune regulation were reviewed. Moreover, efferocytosis process and its impairment in association with some autoimmune diseases were discussed. Keywords: apoptosis, efferocytosis, autoimmune disease, phagocytosis, systemic lupus erythematou

The atherogenic role of immune cells in familial hypercholesterolemia

Familial hypercholesterolemia (FH) is an autosomal dominant disorder of lipoprotein metabolism that mainly occurs due to mutations in the low-density lipoprotein receptor gene and is characterized by increased levels of low-density lipoprotein cholesterol, leading to accelerated atherogenesis and premature coronary heart disease. Both innate and adaptive immune responses, which mainly include monocytes, macrophages, neutrophils, T lymphocytes, and B lymphocytes, have been shown to play a key role for the initiation and progression of atherogenesis in the general population. In FH patients, these immune cells have been suggested to play specific pro-atherosclerotic activities, from the initial leukocyte recruitment to plaque rupture. In fact, the accumulation of cholesterol crystals and oxLDL in the vessels in FH patients is particularly high, with consequent abnormal mobilization of immune cells and secretion of various pro-inflammatory and chemokines. In addition, cholesterol accumulation in immune cells is exaggerated with chronic exposure to relevant pro-atherosclerotic triggers. The topics considered in this review may provide a more specific focus on the immune system alterations in FH and open new insights toward immune cells as potential therapeutic targets in FH

The complex roles of efferocytosis in cancer development, metastasis, and treatment

When tumor cells are killed by targeted therapy, radiotherapy, or chemotherapy, they trigger their primary tumor by releasing pro-inflammatory cytokines. Microenvironmental interactions can also promote tumor heterogeneity and development. In this line, several immune cells within the tumor microenvironment, including macrophages, dendritic cells, regulatory T-cells, and CD8+ and CD4+ T cells, are involved in the clearance of apoptotic tumor cells through a process called efferocytosis. Although the efficiency of apoptotic tumor cell efferocytosis is positive under physiological conditions, there are controversies regarding its usefulness in treatment-induced apoptotic tumor cells (ATCs). Efferocytosis can show the limitation of cytotoxic treatments, such as chemotherapy and radiotherapy. Since cytotoxic treatments lead to extensive cell mortality, efferocytosis, and macrophage polarization toward an M2 phenotype, the immune response may get involved in tumor recurrence and metastasis. Tumor cells can use the anti-inflammatory effect of apoptotic tumor cell efferocytosis to induce an immunosuppressive condition that is tumor-tolerant. Since M2 polarization and efferocytosis are tumor-promoting processes, the receptors on macrophages act as potential targets for cancer therapy. Moreover, researchers have shown that efferocytosis-related molecules/pathways are potential targets for cancer therapy. These include phosphatidylserine and calreticulin, Tyro3, Axl, and Mer tyrosine kinase (MerTK), receptors of tyrosine kinase, indoleamine-2,3-dioxygenase 1, annexin V, CD47, TGF-β, IL-10, and macrophage phenotype switch are combined with conventional therapy, which can be more effective in cancer treatment. Thus, we set out to investigate the advantages and disadvantages of efferocytosis in treatment-induced apoptotic tumor cells