Human smooth muscle myosin heavy chain isoforms as molecular markers for vascular development and atherosclerosis

Masanori Aikawa, Palanisamy Nalla Sivam, Makoto Kuro-o, Kenjiro Kimura, Ken Ichi Nakahara, Shun Ichi Takewaki, Makiko Ueda, Hiroshi Yamaguchi, Yoshio Yazaki, Muthu Periasamy, Ryozo Nagai

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292 Scopus citations

Abstract

Smooth muscle myosin heavy chains (MHCs) exist in multiple isoforms. Rabbit smooth muscles contain at least three types of MHC isoforms: SM1 (204 kD), SM2 (200 kD), and SMemb (200 kD). SM1 and SM2 are specific to smooth muscles, but SMemb is a nonmuscle-type MHC abundantly expressed in the embryonic aorta. We recently reported that these three MHC isoforms are differentially expressed in rabbit during normal vascular development and in experimental arteriosclerosis and atherosclerosis. The purpose of this study was to clarify whether expression of human smooth muscle MHC isoforms is regulated in developing arteries and in atherosclerotic lesions. To accomplish this, we have isolated and characterized three cDNA clones from human smooth muscle: SMHC94 (SM1), SMHC93 (SM2), and HSME6 (SMemb). The expression of SM2 mRNA in the fetal aorta was significantly lower as compared with SM1 mRNA, but the ratio of SM2 to SM1 mRNA was increased after birth. SMemb mRNA in the aorta was decreased after birth but appeared to be increased in the aged. To further examine the MHC expression at the histological level, we have developed three antibodies against human SM1, SM2, and SMemb using the isoform-specific sequences of the carboxyl terminal end. Immunohistologically, SM1 was constitutively positive from the fetal stage to adulthood in the apparently normal media of the aorta and coronary arteries, whereas SM2 was negative in fetal arteries of the early gestational stage. In human, unlike rabbit, aorta or coronary arteries, SMemb was detected even in the adult. However, smaller-sized arteries, like the vasa vasorum of the aorta or intramyocardial coronary arterioles, were negative for SMemb. Diffuse intimai thickening in the major coronary arteries was found to be composed of smooth muscles, reacting equally to three antibodies for MHC isoforms, but reactivities with anti-SM2 antibody were reduced with aging. With progression of atherosclerosis, intimal smooth muscles diminished the expression of not only SM2 but also SM1, whereas α-smooth muscle actin was well preserved. We conclude from these results that smooth muscle MHC isoforms are important molecular markers for studying human vascular smooth muscle cell differentiation as well as the cellular mechanisms of atherosclerosis.

Original languageEnglish (US)
Pages (from-to)1000-1012
Number of pages13
JournalCirculation research
Volume73
Issue number6
DOIs
StatePublished - Dec 1993

Keywords

  • Atherosclerosis
  • Myosin heavy chains
  • Smooth muscle
  • Vascular development

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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    Aikawa, M., Sivam, P. N., Kuro-o, M., Kimura, K., Nakahara, K. I., Takewaki, S. I., Ueda, M., Yamaguchi, H., Yazaki, Y., Periasamy, M., & Nagai, R. (1993). Human smooth muscle myosin heavy chain isoforms as molecular markers for vascular development and atherosclerosis. Circulation research, 73(6), 1000-1012. https://doi.org/10.1161/01.RES.73.6.1000