Abstract 13082: Adiponectin and the Regulation of Vascular Smooth Muscle Cell Phenotype

• Published in: Circulation (New York, N.Y.) N.Y.), 2019-11, Vol.140 (Suppl_1 Suppl 1), p.A13082-A13082
• Main Authors: Cullen, Abigail, Ismaeel, Ahmed, Koutakis, Panagiotis, Salazar, Gloria
• Format: Article
• Language: English
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/circ.140.suppl_1.13082

Adiponectin (Adpn) is a powerful regulator of atheroprotective and anti-inflammatory mechanisms. Adipose tissue was believed to be the primary source of this adipokine, but a variety of cells, including skeletal muscle cells, and vascular smooth muscle cells (VSMCs), can also produce this hormone. The dominating presence of adiponectin in circulation and its beneficial roles in atherosclerosis and diabetes make it of prime interest for cardiovascular research. We hypothesize that adiponectin promotes the contractile phenotype of VSMCs by an AMPK/mitochondrial function-dependent mechanism. VSMCs isolated from aortas of wild type (WT) and Adpn mice were cultured up to passage 12 for the analysis of markers of cell differentiation, proliferation, and signaling through the AMPK pathway, as well as cellular respiration using an Oroboros Oxygraph System. Cell proliferation was assessed by measuring cell number in an haemocytometer chamber. To assess the role of AMPK, cells were treated with metformin, AICAR and AdipoRon, an activator of adiponectin receptors. Adpn cells showed increased cell proliferation and expression of markers of cell cycle progression including cyclin D1, compared with WT cells, which correlated with reduced expression of the differentiation genes smooth muscle actin, SM22, myosin heavy chain and calponin. Metformin, AICAR and AdipoRon induced upregulation of AMPK activity in both cell types reducing cyclin D1 expression and cell proliferation in Adpn cells. Similar effects were observed in Adipo cells treated with conditioned media from WT cells, suggesting that VSMCs secrete Adpn to maintain the differentiated state of these cells. Adpn cells also showed reduced oxidative phosphorylation (OXPHOS) and increased glycolysis. Whether the switch from OXPHOS to glycolysis mediates the phenotypic switch in Adpn cells remains to be investigated. These data showed that Adpn regulates cell metabolism and the expression of differentiation markers to reduce proliferation of VSMCs. This mechanism would be protective in conditions of vascular injury and in disease sates like atherosclerosis in which migration and proliferation of VSMCs contribute to neointima formation and plaque development, respectively.