However, AS region is pathologically featured with extreme hypoxia, which cause the up-regulation of hypoxia-inducible factor 1α (HIF-1α). Normally, the internalized lipid can be digested and then removed from macrophages by different transporters, such as ATP-binding cassette transporter A1 (ABCA1), and G1 (ABCG1). Meanwhile, the macrophages take up excess amount of oxidized low-density lipoprotein (ox-LDL) to form foam cells. The monocytes are recruited into AS site and differentiate into classical pro-inflammatory M1 macrophages, which create a pro-atherogenic local via different mechanisms, such as cytokines excretion and reactive oxygen species (ROS) generation. Therefore, intervention the plaques of AS at early stages is critically important to control the disease progress and save the patients’ lives.ĭuring the progress of AS, macrophages are the central cells in the development, progression, and stability of plaques. The early and steady plaques could exist for many years, while the major risk is the advance and vulnerable plaques that rupture to cause ischemic complications, such as sudden cardiac death, stroke, acute myocardial infraction, and other severe outcomes.
Image pro plus hematoxylin and eosin series#
It is generally accepted that the excessive intake and accumulation of lipid (mainly low-density lipoprotein, LDL) is the initial step of AS, which is internalized by macrophages to trigger a series of subsequent pathological processes, such as chronic inflammatory response, artery intima injury, foam cells formation, and finally, the development of plaques. AS is featured by dysfunction of lipoprotein cholesterol metabolism and the accumulation of plaques underneath the inner wall of the vessel, which is composed of lipids and inflammatory cells. Graphical AbstractĪrteriosclerosis (AS), a chronic and progressive vascular disease, is the major contributor of lethal cardiovascular diseases. As a result, a robust anti-AS efficacy was achieved as evidenced by the decrease of atherosclerotic lesion, plaque area, lipid level. In ApoE−/− mice model, the nanosystem could significantly prolong the circulation half-life of Cur by sixfold, and enhance drug accumulation in atherosclerotic lesion by 3.5-fold after intravenous injection by virtue of surface hyaluronic acid (HA) modification. Collectively, the nanocarrier and the payload drug functioned as an all-active nanoplatform to synergistically alleviate the syndromes of AS. Cur displayed a broad spectrum of anti-oxidant and anti-inflammatory capabilities to repolarize M1 macrophages into M2 phenotype, and the catalytic MnO 2 recovered the function of lipid efflux transporter to remove lipid from cells by suppressing HIF-1α. Moreover, the mesoporous structure as well as the abundant metal coordination sites in MnO 2 structure facilitated the loading of an anti-AS drug of curcumin (Cur), achieving extraordinarily high drug loading capacity of 54%. The MnO 2 was one-pot synthesized under mild condition, showing intrinsic catalase-mimic activity for self-oxygenation by using endogenous H 2O 2 as substrate. In this work, we developed a MnO 2-based nanomedicine to re-educate macrophages for targeting AS therapy. During the development and progress of AS, macrophages play critical roles, which are polarized into pro-inflammatory M1 phenotype to excrete abundant cytokines and overproduce reactive oxygen species (ROS), and take up excess amount of lipid to form foam cells. Atherosclerosis (AS) is a leading cause of vascular diseases that severely threats the human health due to the lack of efficient therapeutic methods.
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