Extracellular matrix disorder and cellular phenotype transformation are the major histopathological features associated with ascending aortic aneurysms. Rare studies have investigated the relationship between cellular phenotype transformation and the abnormalities of the matrix constituents. In this study, we investigated whether the cellular phenotype transformation resulted in the extracellular matrix disorder.Aortic samples were obtained from 20 patients undergoing operations for ascending aortic aneurysms. Control aortic samples were obtained from 15 patients who underwent coronary artery bypass graft. The protein levels of osteopontin (OPN), collagen, and elastin were examined using Western blot, and quantitative reverse transcriptase-PCR was used to analyze the mRNA expression of collagen and elastin. In vitro experiment, vascular smooth muscle cells (VSMCs) were treated with recombinant human OPN (rh-OPN) or p38 MAPK inhibitor (SB203580) to investigate whether OPN and p38 MAPK regulated the expression of collagen and elastin.The protein level of OPN and collagen III increased in ascending aortic aneurysm samples, compared with controls (p < 0.05). There was no difference in the protein level of elastin between aneurysm tissues and the controls. VSMCs treated with rh-OPN increased the collagen III and elastin protein level and mRNA expression (p < 0.05). Cells treated with SB203580 decreased the collagen III and elastin protein level and mRNA expression (p < 0.05). Furthermore, VSMCs incubated with SB203580 reduced the rh-OPN-induced production of collagen III and elastin (p < 0.05).OPN, the proliferative VSMCs maker, increased the expression of extracellular matrix. OPN/p38 MAPK signaling pathways may protect against ascending aortic aneurysm progression.© 2021 S. Karger AG, Basel.