Vascular smooth muscle cells (SMCs), a major structural component of the vessel wall, not only play a key role in maintaining vascular structure but also perform various functions. During ...embryogenesis, SMC recruitment from their progenitors is an important step in the formation of the embryonic vascular system. SMCs in the arterial wall are mostly quiescent but can display a contractile phenotype in adults. Under pathophysiological conditions, i.e. vascular remodelling after endothelial dysfunction or damage, contractile SMCs found in the media switch to a secretory type, which will facilitate their ability to migrate to the intima and proliferate to contribute to neointimal lesions. However, recent evidence suggests that the mobilization and recruitment of abundant stem/progenitor cells present in the vessel wall are largely responsible for SMC accumulation in the intima during vascular remodelling such as neointimal hyperplasia and arteriosclerosis. Therefore, understanding the regulatory mechanisms that control SMC differentiation from vascular progenitors is essential for exploring therapeutic targets for potential clinical applications. In this article, we review the origin and differentiation of SMCs from stem/progenitor cells during cardiovascular development and in the adult, highlighting the environmental cues and signalling pathways that control phenotypic modulation within the vasculature.
Atherosclerosis is a highly prevalent disease that can significantly increase the risk of major vascular events, such as myocardial or cerebral infarctions. The anoxemia theory states that a ...disparity between oxygen supply and demand contributes to atherosclerosis. Hypoxia inducible factor-1 (HIF-1) is a heterodimeric protein, part of the basic helix-loop-helix family and one of the main regulators of cellular responses in a low‑oxygen environment. It plays a key role in the development of atherosclerosis through cell-specific responses, acting on endothelial cells, vascular smooth muscle cells (SMCs) and macrophages. Through the upregulation of VEGF, NO, ROS and PDGF, HIF-1 is able to cause endothelial cell dysfunction, proliferation, angiogenesis and inflammation. Activation of the NF-kB pathway in endothelial cells is an important contributor to inflammation and positively feedbacks to HIF-1. HIF-1 also plays a significant role in both the proliferation and migration of smooth muscle cells – two important features of atherosclerosis, while the formation of foam cells (lipid-laden macrophages) is also a critical step in atherosclerosis and mediated by HIF-1 through various mechanisms such as dysfunctional efflux pathways in macrophages. Overall, HIF-1 exerts its effect on the pathogenesis of atherosclerosis via a variety of molecular and cellular events in the process. In this review article, we examine the effects HIF-1 on vascular cells and macrophages in the development of atherosclerosis, highlighting the environmental cues and signalling pathways that control HIF-1 expression/activation within the vasculature. We will highlight the potential of HIF-1 as a therapeutic target on the disease development.
Development of efficient therapeutic strategy to incorporate ultrasound (US)-triggered sonodynamic therapy (SDT) and ferroptosis is highly promising in cancer therapy. However, the SDT efficacy is ...severely limited by the hypoxia and high glutathione (GSH) in the tumor microenvironment, and ferroptosis is highly associated with reactive oxygen species (ROS) and GSH depletion.
A manganese porphyrin-based metal-organic framework (Mn-MOF) was constructed as a nanosensitizer to self-supply oxygen (O
) and decrease GSH for enhanced SDT and ferroptosis.
and
analysis, including characterization, O
generation, GSH depletion, ROS generation, lipid peroxidation, antitumor efficacy and tumor immune microenvironment were systematically evaluated.
Mn-MOF exhibited catalase-like and GSH decreasing activity
. After efficient internalization into cancer cells, Mn-MOF persistently catalyzed tumor-overexpressed H
O
to
produce O
to relieve tumor hypoxia and decrease GSH and GPX4, which facilitated the formation of ROS and ferroptosis to kill cancer cells upon US irradiation in hypoxic tumors. Thus, strong anticancer and anti-metastatic activity was found in H22 and 4T1 tumor-bearing mice after a single administration of Mn-MOF upon a single US irradiation. In addition, Mn-MOF showed strong antitumor immunity and improved immunosuppressive microenvironment upon US irradiation by increasing the numbers of activated CD8
T cells and matured dendritic cells and decreaing the numbers of myeloid-derived suppressor cells in tumor tissues.
Mn-MOF holds great potential for hypoxic cancer therapy.
Recent studies showed that lipoprotein(a) Lp(a) is a causal risk factor for cardiovascular disease (CVD). However, whether Lp(a) modifies clinical risk assessment was not established.
This study was ...conducted to determine whether Lp(a) improves CVD risk prediction.
In 1995, Lp(a) was measured in 826 men and women (age range, 45 to 84 years) from the general community. Incidence of CVD was recorded over 15 years of follow-up.
In models adjusted for Framingham Risk Score (FRS) and Reynolds Risk Score (RRS) variables, the hazard ratio (HR) for incident CVD was 1.37 per 1-SD higher Lp(a) level (SD = 32 mg/dl) and 2.37 when comparing the top fifth quintile with other quintiles. The addition of Lp(a) to the RRS increased the C-index by 0.016. Of the 502 subjects who remained free of CVD, 82 were correctly reclassified to a lower risk category and 49 were reclassified to a higher risk category (predicted 15-year categories: <7.5%, 7.5% to <15%, 15% to <30%, ≥30%) (p < 0.001). Of the 148 subjects who developed CVD, 18 were correctly reclassified to a higher risk category and 17 were reclassified to a lower risk category. In subjects at intermediate risk (15% to <30%), the net reclassification improvement afforded by Lp(a) was 22.5% for noncases, 17.1% for cases, and 39.6% overall. Allele-specific Lp(a) levels did not add to the predictive ability of the FRS or RRS or to Lp(a).
Elevated Lp(a) predicts 15-year CVD outcomes and improves CVD risk prediction. These findings suggest that Lp(a) levels may be used in risk assessment of subjects in the general community, particularly in intermediate-risk groups.
Vascular, resident stem cells are present in all 3 layers of the vessel wall; they play a role in vascular formation under physiological conditions and in remodeling in pathological situations. ...Throughout development and adult early life, resident stem cells participate in vessel formation through vasculogenesis and angiogenesis. In adults, the vascular stem cells are mostly quiescent in their niches but can be activated in response to injury and participate in endothelial repair and smooth muscle cell accumulation to form neointima. However, delineation of the characteristics and of the migration and differentiation behaviors of these stem cells is an area of ongoing investigation. A set of genetic mouse models for cell lineage tracing has been developed to specifically address the nature of these cells and both migration and differentiation processes during physiological angiogenesis and in vascular diseases. This review summarizes the current knowledge on resident stem cells, which has become more defined and refined in vascular biology research, thus contributing to the development of new potential therapeutic strategies to promote endothelial regeneration and ameliorate vascular disease development.
Vascular smooth muscle cells (VSMCs) play a role in the development of vascular disease, for example, neointimal formation, arterial aneurysm, and Marfan syndrome caused by genetic mutations in ...VSMCs, but little is known about the mechanisms of the disease process. Advances in induced pluripotent stem cell technology have now made it possible to derive VSMCs from several different somatic cells using a selection of protocols. As such, researchers have set out to delineate key signaling processes involved in triggering VSMC gene expression to grasp the extent of gene regulatory networks involved in phenotype commitment. This technology has also paved the way for investigations into diseases affecting VSMC behavior and function, which may be treatable once an identifiable culprit molecule or gene has been repaired. Moreover, induced pluripotent stem cell-derived VSMCs are also being considered for their use in tissue-engineered blood vessels as they may prove more beneficial than using autologous vessels. Finally, while several issues remains to be clarified before induced pluripotent stem cell-derived VSMCs can become used in regenerative medicine, they do offer both clinicians and researchers hope for both treating and understanding vascular disease. In this review, we aim to update the recent progress on VSMC generation from stem cells and the underlying molecular mechanisms of VSMC differentiation. We will also explore how the use of induced pluripotent stem cell-derived VSMCs has changed the game for regenerative medicine by offering new therapeutic avenues to clinicians, as well as providing researchers with a new platform for modeling of vascular disease.
Accumulating evidence indicates the impact of endothelial progenitor cells (EPCs) in vascular repair. In patients, the number of EPCs is negatively correlated with the severity of atherosclerosis. In ...various animal models, transplantation of bone marrow-derived progenitor cells could sufficiently rescue organ function and enhance vascular repair and tissue regeneration. Increase in the number of circulating progenitors, induced by cell transfusion or enhanced mobilization, can also enhance restoration and integrity of the endothelial lining, suppress neointimal formation, and increase blood flow to ischaemic sites. However, the beneficial outcome of EPC infusion very much depends on the growth and differentiation factors within the tissue, cell-to-cell interactions, and the degree of injury. As highlighted by several studies, EPCs derive from different sources including bone marrow and non-bone marrow organs such as the spleen, the functional repair properties of which may vary with the maturation state of the cell. Thus, understanding the molecular mechanisms involved in EPC-repairing processes is essential. In the present review we focus on the role of EPCs in vascular diseases, and we provide an update on the mechanisms of EPC mobilization, homing, and differentiation.
Physiologically, endothelial integrity and smooth muscle homeostasis play key roles in the maintenance of vascular structure and functions. Under pathological conditions, endothelial and smooth ...muscle cells display great plasticity by transdifferentiating into other cell phenotypes. This review aims to update the progress in endothelial and smooth muscle cell transformation and to discuss their underlying mechanisms.
At the early stage of atherosclerosis, it was traditionally believed that smooth muscle cells from the media migrate into the intima in which they proliferate to form neointimal lesions. Recently, endothelial cells were shown to undergo transformation to form smooth muscle-like cells that contribute to neointimal formation. Furthermore, not only can medial smooth muscle cells migrate and proliferate, they also have the ability to differentiate into macrophages in the intima in which they form foam cells by uptaking lipids. Finally, the discovery of stem/progenitor cells in the vessel wall that can differentiate into all types of vascular cells has complicated the research field even further.
Based on the current progress in the research field, it is worthy to explore the contributions of cell transformation to the pathogenesis of atherosclerosis to understand the mechanisms on how they are regulated in order to develop novel therapeutic application targeting these processes to reverse the disease progression.
kImmobilizing inorganic particles such as zinc oxide (ZnO), titanium dioxide (TiO
2
), silver nanoparticles (Ag NPs) or grafting special biopolymer such as chitosan on cotton fabrics is the main ...method to prepare antibacterial and ultraviolet (UV) protective cotton fabrics. However, poor durability and complex finishing methods are still of the main defects of antibacterial and UV protective fabric samples. In the present work, the Ag/TiO
2
colloid solution was prepared with using the carboxymethyl chitosan (CMC) as a stabilizer, then the CMC and Ag/TiO
2
composite nanoparticles were coated on the fabric via finishing technology of pad-dry-cure. As a result, the modified fabric showed excellent antibacterial and UV protective properties, with the values of bacterial reduction (BR) and ultraviolet protection factor were reached at 99.5 % and 79.0, respectively. Moreover, even after 50 washing cycles, these properties of the finished fabrics were not obviously reduced. These results demonstrated that the finished fabric sample has durable antibacterial and UV protective properties which could has a great potential application in the field of medical and outdoor apparel.
Mesenchymal stem cells and vascular regeneration Gu, Wenduo; Hong, Xuechong; Potter, Claire ...
Microcirculation (New York, N.Y. 1994),
January 2017, 2017-01-00, 20170101, Letnik:
24, Številka:
1
Journal Article
Recenzirano
Odprti dostop
In recent years, MSCs have emerged as a promising therapeutic cell type in regenerative medicine. They hold great promise for treating cardiovascular diseases, such as myocardial infarction and limb ...ischemia. MSCs may be utilized in both cell‐based therapy and vascular graft engineering to restore vascular function, thereby providing therapeutic benefits to patients. The efficacy of MSCs lies in their multipotent differentiation ability toward vascular smooth muscle cells, endothelial cells and other cell types, as well as their capacity to secrete various trophic factors, which are potent in promoting angiogenesis, inhibiting apoptosis and modulating immunoreaction. Increasing our understanding of the mechanisms of MSC involvement in vascular regeneration will be beneficial in boosting present therapeutic approaches and developing novel ones to treat cardiovascular diseases. In this review, we aim to summarize current progress in characterizing the in vivo identity of MSCs, to discuss mechanisms involved in cell‐based therapy utilizing MSCs, and to explore current and future strategies for vascular regeneration.
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