Adeylyl cyclase 8 over-expression in vascular smooth muscle promotes the acquisition of inflammatory/migratory phenotype and development of pulmonary hypertension

• DOI: 10.1016/j.rmr.2015.02.058
• Publication Date: 2015-04-03T23:20:11Z
• Authors: B. Vallin; A. Houssaini; S. Abid; C. Rouxel; S. Adnot; G. Derumeaux; I. Limon; L. Lipskaia
• Keywords: 03 medical and health sciences; 0302 clinical medicine

Background Adenylyl cyclases (AC), the principal control of cyclic AMP (cAMP) signaling pathway, are differently expressed in quiescent and remodeled vascular smooth muscle cells (SMCs). Particularly, the induction of AC8 isoform was reported in the inflammatory/migratory phenotype together with induction of metalloproteinases (MMPs 2 and 9) (Keuylian et al., 2012). Here, we investigated whether selective AC8 expression in VSMCs was sufficient to induce pulmonary hypertension (PH) in mice. Methods Transgenic mice carrying human AC8 cDNA under a-MHC promoter (AC8TG) were used (Lipskaia et al., 2000). We studied three groups of mice aged 3, 7 and 12 months. Standard procedures were used to assess heart function and the morphologic characteristics of pulmonary muscular arteries. RNA expression was determined using real-time RT-PCR analysis. Results No difference in basal cardiac function was detected in young mice (2–6-month-old). Starting from 8 months echocardiographic analysis revealed progressive increase of contractile function evaluated by LVED and LVES diameters, ED and ES volumes; and decrease of EF (%) and FS (%) compared to their littermates. At the end point (12 months) AC8TM exhibited an increased heart weight/tibia length ratio (1.02 ± 0.13 vs. 0.77 ± 0.11, P P P Conclusion Adeylyl cyclase 8 over-expression in PA-SMC promotes the acquisition of inflammatory/migratory phenotype and development of pulmonary hypertension.