title: JE mRNA accumulates rapidly in aortic injury and in platelet-derived growth factor-stimulated vascular smooth muscle cells.
abstract: The early response to vascular injury is characterized by migration of inflammatory cells, including monocytes, and platelets to the damaged vessel wall. These inflammatory cells may serve as a source of growth factors and cytokines that stimulate vascular smooth muscle cell (VSMC) migration and proliferation associated with intimal hyperplasia. JE is a platelet-derived growth factor (PDGF)-inducible "early" gene that encodes a monocyte chemoattractant and, as such, could play an important role in inflammation. We now report that JE mRNA levels are increased in intact aorta after balloon injury. The time course of this increase, with maximal levels at 4 hours, is similar to that seen in PDGF-treated cultured rat aortic VSMCs. The accumulation of JE mRNA in cultured VSMCs is accompanied by a marked increase in the secretion of JE protein. The elevation of JE mRNA levels in VSMCs shows specificity for PDGF, because angiotensin II, alpha-thrombin, and epidermal growth factor fail to increase JE mRNA levels. In contrast to 3T3 fibroblasts, the accumulation of JE mRNA in VSMCs in response to PDGF is predominantly due to an increase in JE mRNA stability. The accumulation of JE mRNA in VSMCs stimulated by PDGF appears to occur via a novel pathway(s) independent of Ca2+ mobilization, Na(+)-H+ exchange, protein kinase C activation, or elevation in cAMP levels. These findings suggest that VSMCs may take part in the early inflammatory response after injury through the production of JE, a potent monocyte chemoattractant. Finally, our data suggest that JE may be a marker for PDGF-specific effects on VSMCs, both in vitro and in vivo. Thus, in addition to direct effects on VSMC growth and migration, PDGF may play a role in the early inflammatory response after vascular injury by inducing chemoattractants, such as that encoded by JE.
authors.affiliation: Brookdale Center for Molecular Biology, Mount Sinai School of Medicine, New York, N.Y. 10029.
authors.forename: M B
authors.initials: MB
authors.lastname: Taubman
authors.forename: B J
authors.initials: BJ
authors.lastname: Rollins
authors.forename: M
authors.initials: M
authors.lastname: Poon
authors.forename: J
authors.initials: J
authors.lastname: Marmur
authors.forename: R S
authors.initials: RS
authors.lastname: Green
authors.forename: B C
authors.initials: BC
authors.lastname: Berk
authors.forename: B
authors.initials: B
authors.lastname: Nadal-Ginard
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000293:injuries* / Q000503:physiopathology; D002478:Cells, Cultured; D018932:Chemokine CCL2; D002630:Chemotactic Factors / Q000235:genetics*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D015398:Signal Transduction; D014947:Wounds and Injuries / Q000378:metabolism*
chemical_list: D018932:Chemokine CCL2; D002630:Chemotactic Factors; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D000804:Angiotensin II