Alterations in phenotype and gene expression of adult human aneurysmal smooth muscle cells by exogenous nitric oxide

• Published in: Experimental cell research 2019-11, Vol.384 (1), p.111589-111589, Article 111589
• Main Authors: Farrell, Kurt, Simmers, Phillip, Mahajan, Gautam, Boytard, Ludovic, Camardo, Andrew, Joshi, Jyotsna, Ramamurthi, Anand, Pinet, Florence, Kothapalli, Chandrasekhar R.
• Format: Article
• Language: English
• Subjects: Abdominal aortic aneurysm; Biochemistry, Molecular Biology; Cell modulus; Elastin; Human health and pathology; Life Sciences; LILAS study; Matrix metalloproteinases; Matrix proteins; Nitric oxide
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1016/j.yexcr.2019.111589

Abdominal aortic aneurysms (AAA) are characterized by matrix remodeling, elastin degradation, absence of nitric oxide (NO) signaling, and inflammation, influencing smooth muscle cell (SMC) phenotype and gene expression. Little is known about the biomolecular release and intrinsic biomechanics of human AAA-SMCs. NO delivery could be an attractive therapeutic strategy to restore lost functionality of AAA-SMCs by inhibiting inflammation and cell stiffening. We aim to establish the differences in phenotype and gene expression of adult human AAA-SMCs from healthy SMCs. Based on our previous study which showed benefits of optimal NO dosage delivered via S-Nitrosoglutathione (GSNO) to healthy aortic SMCs, we tested whether such benefits would occur in AAA-SMCs. The mRNA expression of three genes involved in matrix degradation (ACE, ADAMTS5 and ADAMTS8) was significantly downregulated in AAA-SMCs. Total protein and glycosaminoglycans synthesis were higher in AAA-SMCs than healthy-SMCs (p