Lysophosphatidylcholine Potentiates the Mitogenic Effect of Various Vasoactive Compounds on Rabbit Aortic Smooth Muscle Cells.

Abstract

SUMMARYWe examined the mechanism of action of lysophosphatidylcholine (lyso-PC), which is suggested to be involved in the pathogenesis of atherosclerosis and inflamatory disorders, and its interaction with well-known vasoactive compounds such as hydrogen peroxide (H 2 O 2 ), thromboxane A 2 (TX-A 2 ), serotonin (5-HT), angiotensin II (Ang-II), endothelin-1 (ET-1), or urotensin II (U-II) on VSMC proliferation. Growth-arrested rabbit VSMCs were incubated with given concentrations of lyso-PC with H 2 O 2 , TX-A 2 , 5-HT, Ang-II, ET-1, or U-II. [3 H]Thymidine incorporation into DNA was measured as an index of VSMC proliferation. Lyso-PC induced a maximal effect on [ 3 H]thymidine incorporation at a concentration of 15 µM (156%), and its effect was significantly inhibited by the phospholipase C inhibitor U73122 (10 µM), the intracellular antioxidant NAC (400 µM), and the NADPH oxidase inhibitor diphenylene iodonium (1 µM), but not by the MAPK kinase inhibitor (10 µM). Heart J 2002; 43: 409-416)

Urotensin-II and cardiovascular diseases

“…Interestingly, Watanabe et al [35] demonstrated a synergistic effect of U-II on proliferation of SMCs when administered with either serotonin or oxidized low-density lipoprotein (LDL). In support of the latter study, lysophosphatidylcholine, an oxidized phospholipid, also synergistically enhanced U-II-mediated SMC proliferation [36]. This finding has potentially serious pathologic implications because oxidized lipids are a major contributor to atherosclerotic lesion formation.…”

Identification and pharmacological characterization of native, functional human urotensin‐II receptors in rhabdomyosarcoma cell lines

“…[Ca 2+ ] i mobilization was insensitive to both blockade of L‐type Ca 2+ channels (with nifedipine) and inhibition of the Ca 2+ ‐sensitive Ca 2+ release (with ryanodine). [Ca 2+ ] i mobilization was phospholipase C‐dependent (U‐73122 sensitive) in agreement with observations made in frog sartorius muscle and rat and rabbit vascular preparations ( Gibson, 1987 ; Saetrum‐Opgaard et al ., 2000 ; Rossowski et al ., 2002 ; Watanabe et al ., 2002 ; Brailoiu et al ., 2003 ). Although phospholipase C‐mediated [Ca 2+ ] i mobilization is generally transduced by G i/o or G q ‐proteins (e.g.…”

“…U‐II exerts pronounced effects in cardiovascular tissue (vasoconstriction/dilation, cardiac inotropy, hypertrophy; Bottrill et al ., 2000 ; Douglas et al ., 2000 ; Stirrat et al ., 2001 ; Russell et al ., 2001 ; Sauzeau et al ., 2001 ; Watanabe et al ., 2002 ; Tzanidis et al ., 2003 ). Thus, [ 125 I]hU‐II binding was profiled in human coronary artery (hCoASMC, primary cells) and human (T/G HA‐SMC) and rat (SV40LT‐SMC, A‐10, A 7 r 5 ) aortic smooth muscle cells, human brain microvascular endothelial cells (hBMVEC, primary cells) and rat embryonic cardiomyocytes (H9c2 [2‐1]).…”

State-dependent calcium mobilization by urotensin-II in cultured human endothelial cells

“…For example, the effect of U-II was abolished by thapsigargin, indicating the participation of endoplasmic reticulum Ca 2+ pools in rhabdomyosarcoma cell line [27] as well as in frog motor nerve terminals [12]. In rat, rabbit and cat blood vessels [2,32,55,56,61] and in rat cultured astrocytes [16], the effect of U-II was inhibited by the phospholipase C inhibitor U-73122, indicating the involvement of phospholipase-C/IP 3 pathways. In contrast, U-II elevated [Ca 2+ ] i largely by facilitating Ca 2+ entry through plasmalemmal Ca 2+ channels in rat spinal motoneurons [30].…”