Arteriosclerosis, thrombosis, and vascular biology
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Arterioscler. Thromb. Vasc. Biol. · Feb 2014
P21-dependent protective effects of a carbon monoxide-releasing molecule-3 in pulmonary hypertension.
Carbon monoxide-releasing molecules (CORMs) represent a pharmacological alternative to CO gas inhalation. Here, we questioned whether CORM-3, a well-characterized water-soluble CORM, could prevent and reverse pulmonary hypertension (PH) in chronically hypoxic mice and in smooth muscle promoter 22 serotonin transporter mice overexpressing the serotonin transporter in smooth muscle cells (SMCs). ⋯ CORM-3 inhibits pulmonary vascular remodeling via p21, which may represent a useful approach for treating PH.
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Arterioscler. Thromb. Vasc. Biol. · Jan 2014
Cyclic adenosine monophosphate-response element-binding protein mediates the proangiogenic or proinflammatory activity of gremlin.
Angiogenesis and inflammation are closely related processes. Gremlin is a novel noncanonical vascular endothelial growth factor receptor-2 (VEGFR2) ligand that induces a proangiogenic response in endothelial cells (ECs). Here, we investigated the role of the cyclic adenosine monophosphate-response element (CRE)-binding protein (CREB) in mediating the proinflammatory and proangiogenic responses of ECs to gremlin. ⋯ Together, the results underline the tight cross-talk between angiogenesis and inflammation and demonstrate a crucial role of CREB activation in the modulation of the VEGFR2-mediated proinflammatory/proangiogenic response of ECs to gremlin.
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Arterioscler. Thromb. Vasc. Biol. · Jan 2014
Modulation of protein C activation by histones, platelet factor 4, and heparinoids: new insights into activated protein C formation.
Histones are detrimental in late sepsis. Both activated protein C (aPC) and heparin can reverse their effect. Here, we investigated whether histones can modulate aPC generation in a manner similar to another positively charged molecule, platelet factor 4, and how heparinoids (unfractionated heparin or oxygen-desulfated unfractionated heparin with marked decrease anticoagulant activity) may modulate this effect. ⋯ Our data provide a new contextual model of how histones affect aPC generation, and how heparinoid therapy may be beneficial in sepsis. These studies provide new insights into the complex interactions controlling aPC formation and suggest a novel therapeutic interventional strategy.
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Arterioscler. Thromb. Vasc. Biol. · Dec 2013
Crucial role of ROCK2 in vascular smooth muscle cells for hypoxia-induced pulmonary hypertension in mice.
Rho/Rho-kinase (ROCK) pathway in vascular smooth muscle cells (VSMCs) plays an important role in the pathogenesis of cardiovascular diseases, including pulmonary arterial hypertension (PAH). Rho-kinase has 2 isoforms, ROCK1 and ROCK2, with different functions in different cells; ROCK1 for circulating inflammatory cells and ROCK2 for the vasculature. In the present study, we aimed to examine whether ROCK2 in VSMC is involved in the pathogenesis of PAH. ⋯ ROCK2 in VSMC contributes to the pathogenesis of PAH.
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Arterioscler. Thromb. Vasc. Biol. · Dec 2013
Soluble JAGGED1 inhibits pulmonary hypertension by attenuating notch signaling.
Notch signaling has been implicated in the development of pulmonary arterial hypertension (PH) as reflected by increased expression of Notch member proteins that induce the proliferation of pulmonary arterial smooth muscle cells (PASMCs). Soluble Jagged1 (sJag1) has been shown to inhibit Notch signaling in vitro and in vivo; however, its capacity to suppress PH remains unknown. ⋯ Our results demonstrated that the potential therapeutic use of the sJag1 may not only inhibit the proliferation of PASMCs but also restore the PH-PASMCs phenotype from the dedifferentiated to the differentiated state through interference with Notch-Herp2 signaling.