PMID- 34593425 OWN - NLM STAT- MEDLINE DCOM- 20211008 LR - 20211008 IS - 1791-7530 (Electronic) IS - 0250-7005 (Linking) VI - 41 IP - 10 DP - 2021 Oct TI - Anti-inflammatory and Anti-thrombotic Efficacy of Targeted Ultrasound Microbubbles on LPS-induced HUVEC Cells. PG - 4761-4769 LID - 10.21873/anticanres.15291 [doi] AB - BACKGROUND/AIM: The early stage of atherosclerosis (AS) demonstrates a lipid-driven inflammatory cytokine increase. In the present study, we aimed to use ultrasound-targeted microbubble delivery (UTMD) therapy with the Endostar-loaded target microbubbles (MBs) to reduce AS-related inflammatory response. MATERIALS AND METHODS: Normal and lipopolysaccharide (LPS) induced human umbilical vein endothelial cells (HUVECs) were placed in a parallel-plate flow chamber. MBs were perfused through the parallel-plate flow chamber to mimic physiological blood flow. Five groups were set up: G1: Negative control (normal HUVECs); G2: LPS control (LPS induced HUVECs); G3: ICAM-1-loaded-MBs (MBi); G4: Endostar-loaded-MBs (MBe) and G5: Endostar-ICAM-1-loaded-MBs (MBei). mRNA expression of inflammatory factors and release of inflammatory cytokines were detected by RT-PCR and ELISA, respectively. RESULTS: After treatment with MBei, the mRNA expression of cell adhesion molecule-1 (CD31) (p=0.004), endothelin-1 (ET-1) (p=0.010), von willebrand factor (vWF) (p=0.018), extracellular regulated protein kinases (ERK) (p=0.046) and nuclear factor kappa B (NF-kappaB) (p=0.003) were significantly reduced compared to LPS-induced HUVECs. Release of inflammatory cytokines including tissue factor (TF) (p=0.033), tissue factor pathway inhibitor (TF-PI) (p=0.019), ET-1 (p=0.014), vWF (p=0.030) and blood-coagulation factor VIIalpha (FVIIalpha) (p=0.000) were also significantly reduced compared to LPS-induced HUVECs. CONCLUSION: UTMD therapy can inhibit the inflammatory response by reducing atherosclerotic-related inflammatory factors, suggesting a potential treatment at the early-stage of AS. CI - Copyright (c) 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved. FAU - Sun, Jindong AU - Sun J AD - First People's Hospital of Linping District, Hangzhou, P.R. China. FAU - Pan, Shijun AU - Pan S AD - Hangzhou Normal University, Hangzhou, P.R. China. FAU - Yu, Huamin AU - Yu H AD - First People's Hospital of Linping District, Hangzhou, P.R. China. FAU - Hu, Haiqiang AU - Hu H AD - First People's Hospital of Linping District, Hangzhou, P.R. China. FAU - Sun, Y U AU - Sun YU AD - Department of Surgery, UCSD, San Diego, CA, U.S.A. FAU - Yang, Zhijian AU - Yang Z AD - AntiCancer Inc., San Diego, CA, U.S.A. FAU - Hoffman, Robert M AU - Hoffman RM AD - AntiCancer Inc., San Diego, CA, U.S.A. FAU - Yuan, Hong AU - Yuan H AD - First People's Hospital of Linping District, Hangzhou, P.R. China; halloween0708@163.com. LA - eng PT - Journal Article PL - Greece TA - Anticancer Res JT - Anticancer research JID - 8102988 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Endostatins) RN - 0 (Fibrinolytic Agents) RN - 0 (Inflammation Mediators) RN - 0 (Lipopolysaccharides) RN - 0 (Recombinant Proteins) RN - 126547-89-5 (Intercellular Adhesion Molecule-1) RN - GVG18ZDN65 (endostar protein) SB - IM MH - Anti-Inflammatory Agents/chemistry/*pharmacology MH - Atherosclerosis/chemically induced/metabolism/therapy MH - Cell Adhesion MH - Endostatins/chemistry/pharmacology MH - Fibrinolytic Agents/chemistry/*pharmacology MH - Human Umbilical Vein Endothelial Cells/*drug effects/metabolism MH - Humans MH - Inflammation Mediators/metabolism MH - Intercellular Adhesion Molecule-1/immunology/metabolism MH - Lipopolysaccharides/toxicity MH - *Microbubbles MH - Recombinant Proteins/chemistry/pharmacology MH - Ultrasonics OTO - NOTNLM OT - Atherosclerosis OT - LPS-induced HUVECs OT - inflammatory cytokines OT - parallel-plate flow chamber OT - ultrasound microbubbles EDAT- 2021/10/02 06:00 MHDA- 2021/10/09 06:00 CRDT- 2021/10/01 06:10 PHST- 2021/04/23 00:00 [received] PHST- 2021/07/10 00:00 [revised] PHST- 2021/08/20 00:00 [accepted] PHST- 2021/10/01 06:10 [entrez] PHST- 2021/10/02 06:00 [pubmed] PHST- 2021/10/09 06:00 [medline] AID - 41/10/4761 [pii] AID - 10.21873/anticanres.15291 [doi] PST - ppublish SO - Anticancer Res. 2021 Oct;41(10):4761-4769. doi: 10.21873/anticanres.15291.