Statins Attenuate Fibrotic Manifestations of Cardiac Tissue Damage.

Cardiac fibrosis is a maladaptive condition secondary to cardiomyopathy caused by a wide spectrum of stimuli, including myocardial infarction (MI), pressure overload, hyperglycemia, aging, and other factors. Despite having been supposed to be a reparative mechanism, the development of cardiac fibrosis can result in undesirable outcomes like the disruption of excitation-contraction coupling and ventricular hypertrophy, leading finally to heart failure (HF). Statins are known as potent cardioprotective agents widely used to control dyslipidemia; these drugs have exhibited protective effects against manifestations of cardiac fibrosis and hypertrophy. Cumulative evidence has suggested that statins attenuate the severity of fibrotic and hypertrophic manifestations of cardiac damage by affecting a variety of mechanisms like differentiation of myofibroblasts and crosstalk between cells in cardiac tissue as well as altering the expression and function of different molecules involved in cardiac remodeling, including inflammatory cytokines and signaling molecules. It seems that statins can inhibit cardiac fibrosis and hypertrophy not only through their ability to inhibit hydroxymethylglutaryl-CoA reductase but also by their pleiotropic properties. This review aims to discuss the effects of statins on molecular pathways involved in the inhibition of fibrotic and hypertrophic remodeling in the heart, thereby potentially helping to recover proper cardiac size, plasticity, and functioning.

Implications of microRNAs in the Pathogenesis of Atherosclerosis and Prospects for Therapy.

MicroRNAs (miRNAs) are non-coding RNAs containing around 22 nucleotides, which are expressed in vertebrates and plants. They act as posttranscriptional gene expression regulators, fine-tuning various biological processes in different cell types. There is emerging evidence on their role in different stages of atherosclerosis. In addition to regulating the inflammatory cells involved in atherosclerosis, miRNAs play fundamental roles in the pathophysiology of atherosclerosis, such as endothelial cell (EC) dysfunction, the aberrant function of the vascular smooth muscle cell (VSMC) and cholesterol metabolism. Moreover, miRNAs participate in several pathogenic pathways of atherosclerotic plaque development, including their effects on immune cell signaling receptors and lipid uptake. In this study, we review our current knowledge of the regulatory role of miRNAs in various pathogenic pathways underlying atherosclerosis development and also outline potential clinical applications of miRNAs in atherosclerosis.

Antiviral effects of statins.

Introducing statins as possible widely-available drugs for the treatment of viral infections requires an in depth review of their antiviral properties. Despite some inconsistency, a large body of literature data from experimental and clinical studies suggest that statins may have a role in the treatment of viral infections due to their immunomodulatory properties as well as their ability to inhibit viral replication. In the present review, the role that statins may play while interacting with the immune system during viral infections and the possible inhibitory effects of statins on different stages of virus cell cycle (i.e., from fusion with host cell membranes to extracellular release) and subsequent virus transmission are described. Specifically, cholesterol-dependent and cholesterol-independent mechanisms of the antiviral effects of statins are reported.

Cell transfer-based immunotherapies in cancer: A review.

In cell transfer therapy (CTT), immune cells such as innate immune-derived natural killer cells and dendritic cells as well as acquired immune-related T lymphocytes such as tumor-infiltrating lymphocytes and cytokine-activated or genetically modified peripheral blood T cells are used in the management of cancer. These therapies are increasingly becoming the most used treatment modality in cancer after tumor resection, chemotherapy, and radiotherapy. In adoptive cell transfer, the lymphocytes isolated from either a donor or the patient are modified ex vivo and reinfused to target malignant cells. Transferring in vitro-manipulated immune cells produces a continuous antitumor immune response. In this review, we evaluate the recent advances in CTT for the management of various malignancies.

TBX18 transcription factor overexpression in human-induced pluripotent stem cells increases their differentiation into pacemaker-like cells.

BACKGROUND: The discovery of gene- and cell-based strategies has opened a new area to investigate novel approaches for the treatment of many conditions caused by cardiac cell failure. The TBX18 (T-box 18) transcription factor is considered as a prominent factor in the sinoatrial node (SAN) formation during the embryonic development. In this in vitro study, the effect of TBX18 gene expression on human-induced pluripotent-stem-cell-derived cardiomyocytes (hiPS-CMs) to induce pacemaker-like cells was examined. METHODS: The human-dermal-fibroblast-derived iPSCs were transfected using chemical, physical, and Lentiviral methods of TBX18 gene delivery during differentiation into cardiomyocytes (CMs). After the differentiation process through small-molecule-based temporal modulation of the Wnt signaling pathway, the hiPSC-CMs were analyzed using the real-time polymerase chain reaction, immunocytochemistry, immunofluorescence, whole-cell patch-clamp recording, and western blotting to investigate the accuracy of differentiation and identify the effect exerted by TBX18. RESULTS: The hiPS-CMs showed spontaneous beating and expressed specific markers of cardiac cells. The lentiviral-mediated TBX18 delivery was the most efficient method for transfection. The results showed the increment in Connexin 43 expression among untransfected hiPS-CMs, whereas this protein was significantly downregulated followed by TBX18 overexpression. TBX18-hiPSCMs were detected with pacemaker cell features. CONCLUSIONS: It was demonstrated that the TBX18 gene is able to conduct hiPSCs to differentiate into pacemaker-like cells. The TBX18 gene delivery seems to have the potential for the development of biological pacemakers; however, more investigations are still needed to assess its usefulness to fix arrhythmic conditions with SAN failure basis.

Stem Cell-Mediated Angiogenesis in Tissue Engineering Constructs.

Angiogenesis has always been a concern in the field of tissue engineering. Poor vascularization of engineered constructs is a problem for the clinical success of these structures. Among the various methods employed to induce angiogenesis, stem cells provide a promising tool for the future. The present review aims to present the application of stem cells in the induction of angiogenesis. Additionally, it summarizes recent advancements in stem cell-mediated angiogenesis of different tissue engineering constructs.

Gene therapy in cardiovascular diseases: A review of recent updates.

Gene therapy is considered as a promising approach for treating cardiac dysfunction. In this review, we evaluated the clinical trials assessing gene therapy in cardiovascular diseases (CVD) from 2000 to 2017. PubMed and ClinicalTrials.gov (only English language) were searched for clinical trials published between January 2000 and May 2017, using the search terms "gene transfer" OR "gene therapy" and "cardiovascular diseases" and related terms. The trials with sample size lower than 10 patients were excluded. Twenty-six clinical trials on human and animals, including 1543 patients were listed and evaluated. The sample size in 14 trials was lower than 100 patients and in seven trials lower than 20 patients. Eleven trials used plasmid DNA and eight trials used adenovirus, one study used plasmid DNA, adenovirus, and liposome. We detected that gene therapy was a safe approach and improved the symptoms of CVD; however, the effect of gene therapy on the cardiac dysfunction is controversial.