Myosin Isoform Expression in Smooth Muscle Cells during Physiological and Pathological Vascular Remodeling

Abstract

There is substantial evidence indicating that the study of cytoskeletal and cytocontractile protein composition in vascular smooth muscle cells (SMCs) can be valuable in tracing structural changes during vascular remodeling. Recent nucleic acid and protein investigations suggest that myosin can be used as a new specific marker for the identification of SMC phenotypes in some pathological conditions affecting the vascular wall. In view of this new information, it would seem timely to review the structural bases of myosin isoform expression in the vascular smooth muscle system as well as the factors involved in its regulation. A puzzling feature has arisen in recent studies on this topic: the presence of non-muscle myosin variants in SMCs during physiological and pathological vascular remodeling. In the response to injury caused by mechanical, chemical and hormonal factors in animals, characterized by proliferation and migration of vascular SMCs from the media to the intima, there is a partial or complete recapitulation of a myosin isoform pattern pertinent to developing vascular smooth muscle tissue. Analysis of myosin isoform content in the vascular wall also demonstrates that: (1) changes in SMC composition may occur independent of medial SMC migration into intima, and (2) the presence of fetal-type SMCs in the neointima is not necessarily related to specific positional changes of medial SMCs.

Effects of Angiotensin II Type 1 Receptor Antagonist on Smooth Muscle Cell Phenotype in Intramyocardial Arteries from Spontaneously Hypertensive Rats

“…VSMCs express two contractile-type isoforms of SM-MHCs (SM1 and SM2) and two synthetic types of NMHC isoforms (NMHC-B/SMemb and NMHC-A) (9,13). Our findings on the localization of SM-MHCs and NMHCs in the hearts of WKY and SHR agreed with the previous results (15,16), indicating that neither NMHC-A nor NMHC-B/SMemb was a …”

“…Based on the results of the specific localization of SM1, SM2, and GATA-6 in the intramyocardial arteries, we demonstrated that 20-week-old SHR showed a significant phenotypic change of SMCs in the intramyocardial arteries towards the synthetic type compared with 20-week-old WKY. Our results for the phenotypic change of SMCs in the hearts were similar to those reported previously, since VSMCs have been shown to modulate their state of differentiation in response to the activation of the local reninAng system, and this plays a crucial role in proliferation and vascular remodeling in hypertension (4,5,9). In addition, VSMCs from SHR produce Ang II and express phenotypic change toward the synthetic type more than those from WKY, which are independent of hypertension (18,19).…”

“…First, the different effects on the phenotypic change of VSMCs in the intramyocardial arteries could be related to differences in the direct inhibition of Ang II stimulation through the AT1 receptor by FK-739 and enalapril, because it has been reported that Ang II might play an important role in the SMC phenotype change in SHR, but not WKY (9,13,(18)(19)(20), which is mainly controlled through the AT1 receptors (5,21), and an AT1 receptor antagonist has been shown to inhibit the Ang II-induced migration of coronary artery SMCs (22). In addition, the difference in the amount of stimulation through the Ang II type 2 (AT2) receptor may have contributed to the different results between FK-739 and enalapril (5).…”

“…In addition, phenotypic modulation of vascular smooth muscle (SM) cells (VSMCs) induced by Ang II contributes not only to vascular remodeling, but also to the contractile property of SM in hypertension (9). Although the intramyocardial arteries are known to be the major determinant factors of coronary flow reserve (2), the precise mechanisms involved in the beneficial effects of the ACE inhibitors or AT1 receptor antagonists on the phenotypic change of intramyocardial arteries in hypertension remain unclear.…”

Phenotypic diversity and molecular mechanisms of airway smooth muscle proliferation in asthma

“…Maintenance of this contractile phenotype in cultured smooth muscle cells is dependent upon a number of carefully controlled cell culture conditions, specifically cell density, avoidance of foetal bovine serum exposure and a requirement for heparin [14,33]. Although modulation of the contractile phenotype and its role in systemic vascular disease is the subject of intense research by vascular biologists [34,35], little attention has been paid so far to its occurrence in airway disease, although some investigators have drawn parallels in the mechanisms for vascular and airway remodelling [26,27,36]. Nevertheless, there is increasing acceptance that, in primary culture, exposure of airway smooth muscle cells to a mitogenic stimulus (e.g.…”