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Suppression of Cell Proliferation and Macrophage Infiltration with Localized siRNA Delivery in a Murine Model of Intimal Hyperplasia
Intimal hyperplasia limits the durability of peripheral vascular interventions and is associated with cell proliferation and macrophage infiltration. We use an in vivo rat carotid angioplasty model to evaluate inhibition of intimal hyperplasia with localized siRNA delivery targeting Thrombospondin-2 (TSP2) and evaluate its impact on cell proliferation (Ki-67) and macrophage infiltration (CD68).
Source: Journal of Vascular Surgery - May 19, 2022 Category: Surgery Authors: Jennifer R. Li, Max Zhu, Patric Liang, Kimberly Piper, Mauricio Contreras, Leena Pradhan-Nabzdyk, Frank LoGerfo Tags: PC: Poster Competition Source Type: research

Delivery of Thrombospondin-2 Small Interfering RNA for Suppression of Intimal Hyperplasia
Treatments of peripheral arterial disease, which affects>8.5 million individuals in the United States, include angioplasty and stenting and graft bypass. However, these have been limited by the pervasive development of intimal hyperplasia, which leads to in-stent restenosis and reduced graft patency. We propose a novel technique to suppress the progression of intimal hyperplasia using bioengineered hydrogels (ClickGels) for localized small interfering RNA (siRNA) delivery and suppression of thrombospondin-2 (TSP2), an upregulated gene of intimal hyperplasia, in an in vivo rat carotid angioplasty model.
Source: Journal of Vascular Surgery - August 24, 2021 Category: Surgery Authors: Jennifer R. Li, Kimberly Piper, Patric Liang, Max Zhu, Mauricio Contreras, Alexander Stafford, David Mooney, Leena Pradhan-Nabzdyk, Frank Logerfo Tags: PC: Poster Competition Source Type: research

Platelet-derived microvesicles induce calcium oscillations and promote VSMC migration via TRPV4
Conclusions: TRPV4 participated in the calcium oscillations and VSMC migration induced by PMVs. PMVs and the related molecules might be novel therapeutic targets for vascular remodeling during vascular injury.
Source: Theranostics - January 15, 2021 Category: Molecular Biology Authors: Shan-Shan Li, Shuang Gao, Yi Chen, Han Bao, Zi-Tong Li, Qing-Ping Yao, Ji-Ting Liu, Yingxiao Wang, Ying-Xin Qi Tags: Research Paper Source Type: research

TSPO ligands prevent the proliferation of vascular smooth muscle cells and attenuate neointima formation through AMPK activation.
In this study we investigated the role of endogenous TSPO in neointima formation after angioplasty in vitro and in vivo. We established a vascular injury model in vitro by using platelet-derived growth factor-BB (PDGF-BB) to stimulate rat thoracic aortic smooth muscle cells (A10 cells). We found that treatment with PDGF-BB (1-20 ng/mL) dose-dependently increased TSPO expression in A10 cells, which was blocked in the presence of PKC inhibitor or MAPK inhibitor. Overexpression of TSPO significantly promoted the proliferation and migration in A10 cells, whereas downregulation of TSPO expression by siRNA or treatment with TS...
Source: Acta Pharmacologica Sinica - September 11, 2019 Category: Drugs & Pharmacology Authors: Wu LP, Gong ZF, Wang H, Zhou ZS, Zhang MM, Liu C, Ren HM, Yang J, Han Y, Zeng CY Tags: Acta Pharmacol Sin Source Type: research

Translocator protein 18 kDa ligand alleviates neointimal hyperplasia in the diabetic rat artery injury model via activating PKG
This study suggests that TSPO inhibition suppresses the proliferation and migration of VSMCs induced by hyperglycemia, consequently, preventing atherosclerosis and restenosis after angioplasty in diabetic conditions. TSPO may be a potential therapeutic target to reduce arterial remodeling induced by angioplasty in diabetes.
Source: Life Sciences - February 9, 2019 Category: Biology Source Type: research

Intraluminal delivery of thrombospondin-2 small interfering RNA inhibits the vascular response to injury in a rat carotid balloon angioplasty model Research
In an effort to inhibit the response to vascular injury that leads to intimal hyperplasia, this study investigated the in vivo efficacy of intraluminal delivery of thrombospondin-2 (TSP-2) small interfering RNA (siRNA). Common carotid artery (CCA) balloon angioplasty injury was performed in rats. Immediately after denudation, CCA was transfected intraluminally (15 min) with one of the following: polyethylenimine (PEI)+TSP-2 siRNA, saline, PEI only, or PEI+control siRNA. CCA was analyzed at 24 h or 21 d by using quantitative real-time PCR and immunohistochemistry. TSP-2 gene and protein expression were significantly up-regu...
Source: FASEB Journal - January 2, 2017 Category: Biology Authors: Bodewes, T. C. F., Johnson, J. M., Auster, M., Huynh, C., Muralidharan, S., Contreras, M., LoGerfo, F. W., Pradhan-Nabzdyk, L. Tags: Research Source Type: research

Resveratrol promotes endothelial cell wound healing under laminar shear stress through an estrogen receptor α dependent pathway.
Abstract Restenosis is an adverse outcome of angioplasty, characterized by vascular smooth muscle cell (VSMC) hyperplasia. However, therapies targeting VSMC proliferation delay re-endothelialization, increasing the risk of thrombosis. Resveratrol (RESV) inhibits restenosis and promotes re-endothelialization after arterial injury, but in vitro studies assessing RESV-mediated effects on endothelial cell growth contradict these findings. We thus hypothesized that fluid shear stress, mimicking physiological blood flow, would recapitulate RESV-dependent endothelial cell wound healing. Since RESV is an estrogen receptor...
Source: American Journal of Physiology. Heart and Circulatory Physiology - January 24, 2014 Category: Physiology Authors: Yurdagul A, Kleinedler J, McInnis MC, Khandelwal AR, Spence A, Orr AW, Dugas TR Tags: Am J Physiol Heart Circ Physiol Source Type: research

Preferential Secretion of Collagen Type 3 versus Type 1 from Adventitial Fibroblasts Stimulated by TGF-β/Smad3-Treated Medial Smooth Muscle Cells.
Abstract Restenosis, or arterial lumen re-narrowing, occurs in 30-50 % of the patients undergoing angioplasty. Adaptive remodeling is compensatory enlargement of the vessel size, and has been reported to prevent the deleterious effects of restenosis. Our previous studies have shown that elevated transforming growth factor (TGF-β) and its signaling protein Smad3 in the media layer induce adaptive remodeling of angioplastied rat carotid artery accompanying an increase of total collagen in the adventitia. In order to gain insights into a possible role of collagen in Smad3-induced adaptive remodeling, here we have in...
Source: Cellular Signalling - December 29, 2012 Category: Cytology Authors: Goel SA, Guo LW, Shi XD, Kundi R, Sovinski G, Seedial S, Liu B, Kent KC Tags: Cell Signal Source Type: research