Enhanced embryonic nonmuscle myosin heavy chain isoform and matrix metalloproteinase expression in aortic abdominal aneurysm with rapid progression

Abdominal aortic aneurysms (AAAs) are characterized by structural deteriora tion of aortic wall leading to progressive dilatation. The histopathologica l changes in AAAs are particularly evident within the elastic media, which is normally comprised mainly of vascular smooth muscle cells (SMCs). There are vascular myosin heavy chain (MHC) isoforms; SM2 is specifically express ed in differentiated SMCs and SMemb is a nonmuscle-type MHC abundantly expr essed in SMCs of the fetal aorta with an immature phenotype. Although AAA a ltered expression of matrix metalloproteinases (MMPs) and their tissue inhi bitors (TIMPs), pathophysiological role of SMC phenotypic modulation in the AAA progression remains uncertain. To determine whether phenotypic modulat ion in vascular SMCs contributes to arterial medial degeneration, we examin ed MHC expression in SMCs of AAA. Aortic specimens were obtained from patie nts with slowly progressed AAA (n = 12) and rapidly progressed AAA (n = 5), and compared with normal aortic tissue (n = 3). Immunohistochemical staini ng was performed for detection of SMemb, SM2, MMP (types 2 and 9) and TIMP (types 1 and 2). Faint SMemb and abundant SM2 were observed in normal aorta , while the balance shifted to SMemb predominance in AAAs. Compared with sl owly progressed AAA tissue, rapidly expanded AAA tissue demonstrated marked increases in SMemb expression with suppressed SM2. Predominant SMemb expre ssion indicates presence of phenotypic modulated SMCs and enhanced MMP; whi le abundant TIMP was seen in mature SMCs expressing SM2. SMemb expression i s markedly increased in AAA with MMP enhancement, and a significant imbalan ce between SMemb and SM2 results in rapid progression of AAA. (C) 1999 by E lsevier Science Inc.