ArticleHypertension (Dallas, Tex. : 1979)2015
Adenosine Attenuates Human Coronary Artery Smooth Muscle Cell Proliferation by Inhibiting Multiple Signaling Pathways That Converge on Cyclin D.
Article in Hypertension (Dallas, Tex. : 1979), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 34 citations in OpenAlex.
- Adenosine receptor signaling in vascular diseases: from molecular mechanisms to targeted therapeutics.Acta pharmacologica Sinica · 2026Review
- Adenosine and adenosine receptors: a "double-edged sword" in cardiovascular system.Frontiers in pharmacology · 2025Review
- Article
- Dipyridamole and vascular healing following stent implantation.Frontiers in cardiovascular medicine · 2023Article
- NAADP-induced intracellular calcium ion is mediated by the TPCs (two-pore channels) in hypoxia-induced pulmonary arterial hypertension.Journal of cellular and molecular medicine · 2021Article
- Adenosine kinase is critical for neointima formation after vascular injury by inducing aberrant DNA hypermethylation.Cardiovascular research · 2021Article
- Deletion of TRPV4 enhances in vitro wound healing of murine esophageal keratinocytes.Scientific reports · 2020Article
- Characterization of the NPurinergic signalling · 2020Article
- Adenosine, Via AHypertension (Dallas, Tex. : 1979) · 2020Article
- Review
- Blood Platelet Adenosine Receptors as Potential Targets for Anti-Platelet Therapy.International journal of molecular sciences · 2019Review
- Adenosine and the Cardiovascular System.American journal of cardiovascular drugs : drugs, devices, and other interventions · 2019Review
- ENPP1-Fc prevents neointima formation in generalized arterial calcification of infancy through the generation of AMP.Experimental & molecular medicine · 2018Article
- Coordination of ENT2-dependent adenosine transport and signaling dampens mucosal inflammation.JCI insight · 2018Article
- On the G protein-coupling selectivity of the native ABiochemical pharmacology · 2018Article
- A genetic association study of carotid intima-media thickness (CIMT) and plaque in Mexican Americans and European Americans with rheumatoid arthritis.Atherosclerosis · 2018Article
- Involvement of RBP4 in all‑trans retinoic acid induced cleft palate.Molecular medicine reports · 2017Article
- Enhanced Proliferation of Porcine Bone Marrow Mesenchymal Stem Cells Induced by Extracellular Calcium is Associated with the Activation of the Calcium-Sensing Receptor and ERK Signaling Pathway.Stem cells international · 2016Article
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
The goal of this study was to determine whether and how adenosine affects the proliferation of human coronary artery smooth muscle cells (HCASMCs). In HCASMCs, 2-chloroadenosine (stable adenosine analogue), but not N(6)-cyclopentyladenosine, CGS21680, or N(6)-(3-iodobenzyl)-adenosine-5'-N-methyluronamide, inhibited HCASMC proliferation (A2B receptor profile). 2-Chloroadenosine increased cAMP, reduced phosphorylation (activation) of ERK and Akt (protein kinases known to increase cyclin D expression and activity, respectively), and reduced levels of cyclin D1 (cyclin that promotes cell-cycle progression in G1). Moreover, 2-chloroadenosine inhibited expression of S-phase kinase-associated protein-2 (Skp2; promotes proteolysis of p27(Kip1)) and upregulated levels of p27(Kip1) (cell-cycle regulator that impairs cyclin D function). 2-Chloroadenosine also inhibited signaling downstream of cyclin D, including hyperphosphorylation of retinoblastoma protein and expression of cyclin A (S phase cyclin). Knockdown of A2B receptors prevented the effects of 2-chloroadenosine on ERK1/2, Akt, Skp2, p27(Kip1), cyclin D1, cyclin A, and proliferation. Likewise, inhibition of adenylyl cyclase and protein kinase A abrogated 2-chloroadenosine's inhibitory effects on Skp2 and stimulatory effects on p27(Kip1) and rescued HCASMCs from 2-chloroadenosine-mediated inhibition. Knockdown of p27(Kip1) also reversed the inhibitory effects of 2-chloroadenosine on HCASMC proliferation. In vivo, peri-arterial (rat carotid artery) 2-chloroadenosine (20 μmol/L for 7 days) downregulated vascular expression of Skp2, upregulated vascular expression of p27(Kip1), and reduced neointima hyperplasia by 71% (P<0.05; neointimal thickness: control, 37 424±18 371 pixels; treated, 10 352±2824 pixels). In conclusion, the adenosine/A2B receptor/cAMP/protein kinase A axis inhibits HCASMC proliferation by blocking multiple signaling pathways (ERK1/2, Akt, and Skp2) that converge at cyclin D, a key G1 cyclin that controls cell-cycle progression.
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