No abstract

Background-Rho-associated kinase (ROCK), an effector of small GTPase Rho, regulates vascular tone via a calcium sensitization mechanism and plays a key role in the pathogenesis of hypertension. However, its role in vascular growth remains unclear. Methods and Results-Y-27632, a specific ROCK inhibitor, and the overexpression of dominant-negative ROCK suppressed the mitogen-induced DNA synthesis of cultured vascular smooth muscle cells (VSMCs), which indicates the essential role of ROCK in the control of VSMC proliferation in vitro. Y-27632 also suppressed the chemotaxis of VSMCs. Male Wistar rats were systemically given Y-27632 (35 to 70 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 ) through an intraperitoneal infusion. The neointimal formation of balloon-injured carotid arteries was significantly suppressed in Y-27632-treated rats (intima/media ratio, 0.22Ϯ0.02) compared with vehicle-treated rats (intima/media ratio, 0.92Ϯ0.21) or hydralazine-treated rats with a similar blood pressure decrease (intima/media ratio, 1.03Ϯ0.15). The phosphorylation of myosin phosphatase and myosin light chain was elevated in injured arteries in a Y-27632-sensitive manner, indicating the augmentation of ROCK activity in neointimal formation. The downregulation of the cyclin-dependent kinase inhibitor p27 kip1 in injured vessels was reversed by Y-27632 treatment, reflecting the antiproliferative effect of ROCK inhibition in vivo. Conclusions-We conclude that ROCK plays a key role in the process of neointimal formation after balloon injury. Thus, the inhibition of ROCK may be a potential therapeutic strategy for treating vascular proliferative disorders and hypertension. Key Words: atherosclerosis Ⅲ muscle, smooth Ⅲ remodeling Ⅲ signal transduction Ⅲ hypertension E levated vascular tone contributes to the pathogenesis of hypertension. Rho-associated kinase (ROCK), 1 a target of small GTPase Rho, regulates vascular contractility by increasing the level of phosphorylated myosin light chain and thereby elevating the calcium sensitivity of vascular smooth muscle cells (VSMCs). 2 Recently, Uehata et al 3 developed a potent, specific, ROCK inhibitor, Y-27632. The administration of Y-27632 to several hypertensive rat models markedly reduced systolic blood pressure (SBP), implicating ROCK as a key mediator in the pathogenesis of hypertension. 3 We and others have reported that regulators of vascular tone, such as angiotensin II or natriuretic peptides, are also involved in vascular growth. 4 Thus, we postulated that intracellular mechanism(s) should exist that govern both vascular contraction and growth. Using Y-27632 and dominant-negative ROCK, the present study demonstrates that ROCK, the key regulator of vascular contraction, also controls vascular growth in vitro and in vivo. Methods MaterialsY-27632 was obtained from Yoshitomi Pharmaceutical Industries, Osaka, Japan. The pCAG-myc and pCAG-myc-KD-IA plasmids 1 were a gift from T. Ishizaki and S. Narumiya (Kyoto University). The pEXV-myc-N19RhoA was from M. Symons (the Picower Institute for Medical Research), and...

Abstract-Vascular endothelial growth factor

Background-Vein graft disease limits the late results of coronary revascularization. C-type natriuretic peptide (CNP) inhibits the growth of vascular smooth muscle cells. The method may potentially prevent vein graft disease in patients undergoing coronary artery revascularization.

Understanding the causes of the Sino-Japanese disjunctions in plant taxa has been a central question in eastern Asian biogeography, with vicariance or long-distance dispersal often invoked to explain such patterns. Diabelia Landrein (Caprifoliaceae; Linnaeoideae) comprises four shrubby species with a Sino-Japanese disjunct distribution. The species diversification time within Diabelia, covering a long geological history of the formation process of the Sino-Japanese flora, dated back to the middle Oligocene, therefore, Diabelia would be an ideal model to elucidate the biogeographic patterns of Sino-Japanese disjunctions with climate fluctuation. In this study, we analyzed complete plastome sequence data for 28 individuals representing all four species of Diabelia. These 28 plastomes were found to be highly similar in overall size (156 243-157 578 bp), structure, gene order, and content. Our phylogenomic analysis of the plastomes supported a close relationship between Diabelia ionostachya (Nakai) Landrein & R.L. Barrett var. wenzhouensis (S.L. Zhou ex Landrein) Landrein from eastern China and Diabelia spathulata (Siebold & Zucc.) Landrein var. spathulata from Japan. Diabelia serrata (Siebold & Zucc.) Landrein was identified as sister to a population of Diabelia sanguinea (Makino) Landrein from Tochigi in central Japan and D. spathulata Landrein, from Toyama, central Japan. Most Diabelia lineages were estimated to have differentiated 8-28 Mya. Our results indicate that two independent vicariance events could explain the disjunction between Japan and Korea in the mid to late Miocene, and between Zhejiang and Japan in the early Miocene.