SELECTIVE EXPRESSION OF PLATELET-DERIVED GROWTH FACTOR B-CHAIN mRNA BY HUMAN ENDOTHELIAL CELLS AND BY HUMAN PERIPHERAL BLOOD MONOCYTES, BUT NOT BY HUMAN SMOOTH MUSCLE CELLS

Vascular injury may occur by a variety of mechanisms. Episodes of local hypoxia or conditions leading to local generation of thrombin may influence local cells to release growthregulatory molecules such as platelet-derivedgrowth factor (PDGF) in the surrounding connective tissue. The roles of the cells and of PDGF in these processes are not entirely understood, and this prompted us to investigate effects of hypoxia (5% O₂) on cultured human saphenous vein endothelial cells andhuman thoracic aorta smooth muscle cells. Freshly isolated human peripheral blood monocytes were exposed to 3.0 U/ml a-thrombin. PDGF-A and PDGF-B mRNAs were analyzed by Northern blots, and their levels were assessed by dot blots utilizing ³²P nick-translated c^DNA probes. Selective expressionof PDGF-B mRNA occurred in endothelial cells during hypoxia and in monocytes exposed to thrombin. Genes coding for PDGF-A and PDGF-B are expressed cons tit utively, in endothelium, and after 48 hr of hypoxia a nine-fold increase of PDGF-B mRNA is detected (9 pg mRNA/ug total RNA). No detectable levels of mRNA encoding PDGF-A and PDGF-B were observed in freshly isolated monocytes; however, a 4-hr exposure to a-thrombin resulted in a selective and transitory increase in PDGF-B mRNA, amountingto 1 pg mRNA/ug toted RNA. No PDGF-B mRNA wasdetected after 20 hr. Hypoxic conditions did not trigger any selective expression of PDGF-B mRNA in smooth muscle, including arterialsmooth muscle derived from 1-day- and 3-month-old individuals, or from adult venous smoot muscle. However, constitutive expression of PDGF-A mRNA was observed in each of these, amounting to 0.4 pg mRNA/ug total RNA in the 1-day- and 3-month-old cells, and 0.2 pg mRNA/ugtotal RNA in the venous smooth muscle. Our datashow that endothelium and monocytes selectively express PDGF-B mRNA in vitro in response to conditions mimicking those encountered during vascular injury in some in-vivo situation.The data imply that both endothelial cells and monocyte/macrophages may be sources for mitogens that induce intimal hyperplasia and eventually plaque formation.