Roles of exosomal miRNA in vascular aging.

Aging is a major risk factor for human diseases. As global average life expectancy has lengthened, delaying or reducing aging and age-related diseases has become an urgent issue for improving the quality of life. The vascular aging process represents an important link between aging and age-related diseases. Exosomes are small extracellular vesicles (EV) that can be secreted by almost all eukaryotic cells, and they deliver characteristic biological information about donor cells to regulate the cellular microenvironment, mediate signal transmission between neighboring or distant cells, and affect the expression of target genes in recipient cells. Many recent studies have shown that exosomal microribonucleic acids (miRNA) are involved in the regulation of vascular aging by participating in the physiological functions of vascular cells and the destruction and remodeling of the extracellular matrix (ECM). This review summarizes the regulatory functions of exosomal miRNA in vascular aging because they interact with the ECM, and participate in vascular cell senescence, and the regulation of senescence-related functions such as proliferation, migration, apoptosis, inflammation, and differentiation.

Stem cell-derived exosomes: Role in the pathogenesis and treatment of atherosclerosis.

Atherosclerosis (AS) is a chronic inflammatory vascular disease characterized by the accumulation of lipids and inflammatory debris in large arteries, high morbidity, and AS-related disease mortality. AS is a complex process, involving endothelial cell dysfunction and inflammation, smooth muscle cell proliferation, and macrophage activation. However, the currently available therapies for AS are not ideal, thus requiring development of novel treatment strategies. Exosomes are bi-lipid membranous extracellular containing multifarious cargo, such as proteins, lipids, micro ribonucleic acid (miRNAs), messenger RNAs, and long non-coding RNAs. Moreover, exosomes reportedly participate in various AS processes. Specifically, stem cell-derived exosomes can regulate the occurrence and development of AS, exhibiting the ability to overcome the limitations associated with AS treatment and stem cell therapy. In this paper, we review the pathological mechanism of AS and discuss the role of exosomes and stem cell-derived exosomes in AS progression. We conclude by suggesting new therapeutic strategies for treating AS with stem cell-derived exosomes in the hope of improving the clinical treatment of AS.

Biogenesis, Features, Functions, and Disease Relationships of a Specific Circular RNA: CDR1as.

In 2011, Hansen discovered the natural antisense transcript (NAT) of the cerebellar degeneration-related protein 1 gene (CDR1), and further described CDR1 NAT as a circular RNA (CircRNA). CDR1 antisense RNA (CDR1as), which is the official name of CDR1 NAT, is conserved and extensively expressed in most eutherian mammal brains and other specialized tissues. Further studies have elucidated its biogenesis, features, functions, and relationships with diseases. CDR1as is involved in many disease processes as a microRNA (miR) sponge. Therefore, it seems that further research on CDR1as could facilitate the diagnosis and treatment of some diseases, such as cancer and diabetes. However, a detailed analysis of the results of studies on CDR1as revealed that they are inconsistent and make unclear conclusions. In this review, we gathered and analyzed the recent studies about CDR1as in detail and aimed to elucidate accurate conclusions from them.

Circular RNAs in the pathogenesis of atherosclerosis.

Atherosclerosis is a common cause of cardiovascular and cerebrovascular diseases. Noncoding RNAs (ncRNAs), including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs) have attracted substantial attention for their roles in various physiological and pathological processes. In recent years, research on the roles of circRNAs in atherosclerosis has progressed rapidly, and they have been implicated in the pathophysiological processes underlying the development of atherosclerosis, including changes in the functions of endothelial cells (ECs), vascular smooth muscle cells (VSMCs), and macrophages. In this review article, we summarize currently available data regarding the role of circRNAs in atherosclerosis and how circRNAs influence the development of atherosclerosis by regulating ECs, VSMCs, and macrophages. We also discuss their potential as diagnostic biomarkers for coronary artery disease.

Noncoding RNAs in Vascular Aging.

Increases in age are accompanied by vascular aging, which can lead to a variety of chronic diseases, including atherosclerosis and hypertension. Noncoding RNAs (ncRNAs) have become a research hotspot in different fields of life sciences in recent years. For example, these molecules have been found to have regulatory roles in many physiological and pathological processes. Many studies have shown that microRNAs (miRNAs) and long ncRNAs (lncRNAs) also play a regulatory role in vascular aging. Endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) are important components of blood vessels, and the senescence of both cell types promotes the occurrence of vascular aging. This review provides a contemporary update on the molecular mechanisms underlying the senescence of ECs and VSMCs and the regulatory role of miRNAs and lncRNAs in this process.

Exosomal long noncoding RNAs in aging and age-related diseases.

Molecules secreted by cells into the internal environment during aging, including those secreted in exosomes, have long been a matter of concern. Those cells that absorb exosomes, also known as recipient cells, exhibit certain phenotypic changes because of the regulatory role of functional molecules (including proteins and nucleic acids) released in exosomes. Involvement of noncoding RNAs (ncRNAs) in the regulation of aging has received increasing attention, and long ncRNAs (lncRNAs) have become one of the research hotspots in recent years. LncRNAs carried by exosomes play a role in intercellular communication between adjacent and distant cells. Moreover, exosomal lncRNAs promote the decline of organ functions and the development of age-related diseases, including atherosclerosis, Type 2 diabetes, osteoporosis, osteoarthritis, rheumatoid arthritis, Parkinson's disease, multiple sclerosis, and cancer. Here, we review the regulatory roles of exosomal lncRNAs in aging and age-related diseases.

Atorvastatin improves left ventricular remodeling and cardiac function in rats with congestive heart failure by inhibiting RhoA/Rho kinase-mediated endothelial nitric oxide synthase.

The aim of the present study was to investigate the effects and possible mechanisms of atorvastatin (Ato) against chronic heart failure (CHF). A rat model of CHF was established and cardiac functions were assessed using Echocardiography. The expression of RhoA/Rho kinase and endothelial nitric oxide synthase (eNOS) was assessed using western blotting and reverse transcription polymerase chain reaction following 4 weeks of treatment. The three groups assessed in the present study were as follows: The control group (no treatment), the Ato + isopropylnoradrenaline (ISO) group (subcutaneous injections of 340 mg/kg ISO + orally administered 50 mg/kg Ato dissolved in saline; administered once daily) and the ISO group (subcutaneous injections of 340 mg/kg ISO + orally administered with an equal volume of saline; administered once daily). Heart volume and weight in the ISO group were significantly increased compared with the control (C) group (P<0.01), whereas contractility was decreased. The results were reverse for the Ato group when compared with the ISO group (P<0.05). Levels of RhoA/Rho kinase protein and mRNA were significantly increased in the ISO group (P<0.01); however. The mRNA and protein expression of eNOS was significantly decreased (P<0.05) when compared with the C group. The mRNA and protein expression of RhoA/Rho kinase was significantly reduced in the Ato+ISO group compared with the ISO group (P<0.01), whereas the mRNA and protein expression of eNOS was significantly increased (P<0.05). RhoA protein expression was increased in the cytoplasm of the C group and on the cell membrane of the ISO group; however, in the Ato+ISO group, RhoA protein expression on the cell membrane was significantly downregulated when compared with the ISO group (P<0.05). The results of the present study suggest that Ato upregulates eNOS by inhibiting RhoA/Rho kinase overexpression in the myocardial tissue of rats with CHF, thus improving left ventricular remodeling and cardiac function.

[Experimental study on the inflammatory and immune responses of xenogenic acellular dermal matrix transplantation combined with thin split-thickness skin autograft].

OBJECTIVE: To investigate the dynamic process of the inflammatory response and the profile of Th1/Th2 cytokines after xenogenic acellular dermal matrix (ADM) transplantation with thin split-thickness skin autograft overlay. METHODS: SD rats were used in the study. In the control group, thin split-thickness skin autograft (STSG) was transplanted in the full-thickness skin defect of the SD rats; in the experimental group, the xenogenic acellular dermal matrix combined with thin split-thickness skin autograft was transplanted. The inflammatory response was examined histologically and Th1/Th2 cytokine mRNA expression in skin grafts was determined by reverse transcription-polymerase chain reaction. RESULTS: Inflammatory reaction was induced by ADM at the early stage of transplantation and decreased gradually. Th2 cytokine mRNA expression was higher in the ADM group than that of the control group whereas the Th1 cytokine mRNA expression was undetected in both groups. CONCLUSION: Xenogenic acellular dermal matrix is immunogenic. The increased expression of Th2 cytokines may be related to the humoral immune responses and the absence of ADM graft rejection.

[An experimental study on the influence of inhibition of postburn stress on inflammatory reaction in severely scalded rats].

OBJECTIVE: To investigate the influence of hibernation drugs on postburn stress and inflammatory reaction in severely scalded rats. METHODS: Sprague-Dawley rats inflicted with 30% TBSA deep partial thickness scalding were employed as the model. The rats were divided into A (scalding with immediate resuscitation), B (scalding with immediate resuscitation and lytic cocktail), C (scalding with delayed resuscitation), D (scalding with delayed resuscitation and lytic cocktail) and E (sham injury) groups. The rat plasma levels of NE (norepinephrine), E (epinephrine) and DA (dopamine) were determined by HPLC (high performance liquid chromatography) at 3, 6, 12, 24 and 48 postburn hours (PBHs), and the plasma IL-1alpha and PGE(2) levels were detected by ELISA (enzyme-linked immunosorbent assay) and RIA (radioimmunoassay) methods. The NF-kappaB activity in PBMCs (peripheral blood mononuclear cells) was determined by laser scanning confocal microscope. RESULTS: The plasma NE and E levels reached summit at 6 PBH, while those in B group were lowest. But the plasma DA level was similar among all groups at all time points. The plasma IL-1alpha and PGE(2) levels increased continuously, however, the levels were were lower in B than A groups at the same time points, and also that of D were lower than C groups. At the same time points, the levels in B group were lower than those in D group. The NF-kappaB was located in the cytoplasma of PBMCs in E group and in the nucleus in A group at 6 PBH. Furthermore, the NF-kappaB was concentrated more in the cytoplasm than that in the nucleus in B group, while it was more concentrated in the nucleus in C and D groups. CONCLUSION: The secretion of stress hormones could be attenuated by hibernation drugs. The plasma cytokine levels and the nuclear translocation of NF-kappaB in PBMCs could also be modulated by the drugs.

[An observation of the basement membrane remodeling after the combined grafting of xenogenic acellular dermal matrix with autoskin in rats].

OBJECTIVE: To observe the dynamic process of basement membrane remodeling after the combined grafting of xenogenic acellular dermal matrix with autoskin. METHODS: The rat skin wounds were covered with xenogenic porcine acellular dermal matrix overlaid with razor thin autoskin. The skin samples were collected at 1, 2, 3, 4, 8, 12 and 16 post-grafting weeks. The changes in laminin expression in the basement membrane and the ultrastructure of the basement membrane at 12 post-grafting weeks were observed by immunohistochemistry and transmission electron microscopy. The results were compared with those in simple thin autoskin grafting as the control. RESULTS: The laminin expression in the combined grafting was higher than that in control. At 12 post-grafting weeks, the basement membrane in combined grafting rats was clear and continuous and the hemidesmosome was relatively more in amount and distributed evenly. While in the autoskin group, the lamina densa in the basement membrane was blurred and discontinuous with a decrease in and uneven distribution of hemidesmosome. CONCLUSION: The increased expression of laminin in the basement membrane in the combined grafting rats might be beneficial to the remodeling of the basement membrane and to strengthening the connection of epithelium to the dermis, thus wound healing quality would be improved.