155 research outputs found
Fine-Tuning Endothelial Notch: SIRT-ainly an Unexpected Mechanism
No full textGuarani et al. (2011), reporting in Nature, identify a mechanism for fine-tuning endothelial Notch signaling by SIRT1-mediated deacetylation. This regulation is critical for vascular sprouting and raises intriguing questions about therapeutic targeting of SIRT1 in angiogenesis and the potential mechanisms that link vascular growth and energy homeostasis
"Large eaters" meet blood vessels: a new thematic series on macrophages and angiogenesis
No full textVascular Cell has launched a new series on macrophages and angiogenesis, a quickly evolving field critical to blood and lymphatic vessels during development, inflammation and tumorigenesis
A selective microRNA-based strategy inhibits restenosis while preserving endothelial function
No full textDrugs currently approved to coat stents used in percutaneous coronary interventions do not discriminate between proliferating vascular smooth muscle cells (VSMCs) and endothelial cells (ECs). This lack of discrimination delays reendothelialization and vascular healing, increasing the risk of late thrombosis following angioplasty. We developed a microRNA-based (miRNA-based) approach to inhibit proliferative VSMCs, thus preventing restenosis, while selectively promoting reendothelialization and preserving EC function. We used an adenoviral (Ad) vector that encodes cyclin-dependent kinase inhibitor p27(Kip1) (p27) with target sequences for EC-specific miR-126-3p at the 3' end (Ad-p27-126TS). Exogenous p27 overexpression was evaluated in vitro and in a rat arterial balloon injury model following transduction with Ad-p27-126TS, Ad-p27 (without miR-126 target sequences), or Ad-GFP (control). In vitro, Ad-p27-126TS protected the ability of ECs to proliferate, migrate, and form networks. At 2 and 4 weeks after injury, Ad-p27-126TS-treated animals exhibited reduced restenosis, complete reendothelialization, reduced hypercoagulability, and restoration of the vasodilatory response to acetylcholine to levels comparable to those in uninjured vessels. By incorporating miR-126-3p target sequences to leverage endogenous EC-specific miR-126, we overexpressed exogenous p27 in VSMCs, while selectively inhibiting p27 overexpression in ECs. Our proof-of-principle study demonstrates the potential of using a miRNA-based strategy as a therapeutic approach to specifically inhibit vascular restenosis while preserving EC function
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