Objectives-We have previously reported that vascular injury or treatment of cultured vascular smooth muscle cells with platelet-derived growth factor-BB (PDGF-BB) or fibroblast growth factor-2 (FGF2) increases the levels of protein tyrosine phosphatase (PTP)1B. The current study was designed to test the hypothesis that PTP1B attenuates PDGF-or FGF-induced motility and proliferation of cultured cells, as well as neointima formation in injured rat carotid arteries. Methods and Results-Treatment of cultured cells with adenovirus expressing PTP1B decreased PDGF-BB-or FGF2-induced cell motility and blocked PDGF-BB-or FGF2-induced proliferation, whereas expression of dominant negative PTP1B (C215S-PTP1B) uncovered the motogenic effect of subthreshold levels of PDGF-BB or FGF2, increased neointimal and medial cell proliferation, and induced neointimal enlargement after balloon injury. The inhibitory effect of PTP1B directed against PDGF in cultured cells was associated with dephosphorylation of the PDGF␤ receptor. Conclusions-PTP1B suppresses cell proliferation and motility in cultured smooth muscle cells treated with PDGF-BB or FGF2, and the phosphatase plays a counter-regulatory role in vascular injury-induced cell proliferation and neointima formation. Taken together with previous studies indicating increased PTP1B levels in cells treated with growth factors, the current findings are the first to report the existence of an inhibitory feedback loop involving PDGF or FGF, and PTP1B in blood vessels. Key Words: PTP1B Ⅲ growth factors Ⅲ neointima formation Ⅲ cell motility Ⅲ cell proliferation M igration and proliferation of smooth muscle cells are of critical importance in neointima formation and remodeling occurring in response to vascular injury. 1 Increased release of platelet-derived growth factor (PDGF) and/or fibroblast growth factor-2 (FGF2), followed by activation of PDGF and/or FGF2 receptor tyrosine kinase activities, are thought to be major events contributing to vascular remodeling. 2 Several reports indicate that injury-induced movement of smooth muscle cells from media to intima and the proliferation of smooth muscle cells in intima are significantly reduced by pharmacological antagonists of the function or availability of PDGF or FGF2. [3][4][5][6][7] Conversely, administration of PDGF-BB or FGF2 has been reported to enhance smooth muscle cell movement from media to intima, followed by cell proliferation in vessels with minimal endothelial damage. 7,8 These studies indicate that PDGF and FGF are important mediators of neointima formation in models of vascular injury. Tyrosyl phosphorylation of growth factor receptors via their intrinsic tyrosine kinase activities is a pivotal event for activation of downstream signaling that mediates increased motility and proliferation in cultured cells. Furthermore, balloon injury or treatment in vivo with PDGF also induces PDGF receptor tyrosyl phosphorylation in vascular smooth muscle, 6,9 a finding consistent with experiments in vitro.Protein tyrosine phosphatases ...

Substance P and neurokinin A are tachykinins that are co-localized with calcitonin gene-related peptide (CGRP) in a unique subpopulation of cardiac afferent nerve fibers. These neurons are activated by nociceptive stimuli and exhibit both sensory and motor functions that are mediated by the tachykinins and/or CGRP. Sensory signals (e.g., cardiac pain) are transmitted by peptides released at central processes of these neurons, whereas motor functions are produced by the same peptides released from peripheral nerve processes. This review summarizes our current understanding of intracardiac actions of the tachykinins. The major targets for the tachykinins within the heart are the intrinsic cardiac ganglia and coronary arteries. Intrinsic cardiac ganglia contain cholinergic neurons that innervate the heart and coronary vasculature. Tachykinins can stimulate NK3 receptors on these neurons to increase their excitability and evoke spontaneous firing of action potentials. This action provides a mechanism whereby tachykinins can indirectly influence cardiac function and coronary tone. Tachykinins also have direct effects on coronary arteries to decrease or increase tone. Stimulation of NK1 receptors on the endothelium causes vasodilation mediated by nitric oxide. This effect is normally dominant, but NK2 receptor-mediated vasoconstriction can also occur and is augmented when NK1 receptors are blocked. It is proposed that these ganglion stimulant and vascular actions are manifest by endogenous tachykinins during myocardial ischemia.

Background: It is unclear how stress granule (SG) formation and cellular apoptosis are coordinately regulated. Results: Monocyte chemotactic protein-induced protein 1 (MCPIP1) inhibited the assembly of SGs and promoted cellular apoptosis under stress. Conclusion: MCPIP1 coordinately regulates SG formation and apoptosis during cellular stress. Significance: MCPIP1 may play a critical role in immune homeostasis and resolution of macrophage inflammation through this mechanism.

Migration and proliferation of vascular smooth muscle cells are key events in injury-induced neointima formation. Several growth factors and ANG II are thought to be involved in neointima formation. A recent report indicated that vascular injury is associated with increased mRNA levels of protein tyrosine phosphatase (PTP)-1B (PTP-1B). In the present study, we tested the following hypotheses: 1) rat carotid artery injury induces the expression of PTP-1B, Src homology-2 domain phosphatase (SHP-2), and PTP-proline, glutamate, serine, and threonine sequence (PEST) protein; and 2) polypeptide growth factors as well as ANG II increase the levels of tyrosine phosphatases in cultured rat aortic smooth muscle cells. We found that vascular injury induced by balloon catheter increases the protein levels of aforementioned phosphatases and that these effects occur in a PTP specific, as well as temporally and regionally specific, manner. Moreover, treatment of cultured primary rat aortic smooth muscle cells with PDGF or bFGF, but not with IGF1, EGF, or ANG II, increases PTP-1B, SHP-2, and PTP-PEST protein levels. These results suggest that increased PDGF and bFGF levels, occurring after vascular injury, may induce expression of several PTPs.

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