OBJECTIVE: The molecular basis of vascular response to hypertension is largely unknown. Both cellular and extracellular components are critical. In the current study we tested the hypothesis that there is a balance between vascular cell proliferation and cell death during vessel remodeling in response to hypertension. METHODS: A midthoracic aortic coarctation was created in rats to induce an elevation of blood pressure proximal to the coarctation. The time course was 1 and 3 days and 1, 2, and 4 weeks for the study of the proximal aorta. Ribonuclease protection assay and Western blot analysis were used to evaluate gene expression of growth and apoptosis-related cytokines with two sets of multiple probes, rCK-3 and rAPO-1. Cell proliferation was determined with BrdU (5-bromo-2'-deoxyuridine) incorporation. Apoptosis was examined with TUNEL (transferase-mediated dUTP nick end-labeling). Morphometry was performed on histologic sections. RESULTS: Coarctation produced hypertension in the proximal aorta, 118 +/- 9 mm Hg versus 94 +/- 6 mm Hg in controls (P <.002). Both messenger RNA and protein levels of transforming growth factor (TGF)-beta1 and TGF-beta3 were increased (P <.005 vs controls). Messenger RNA and protein of Bcl-xS and Fas ligand, known as proapoptotic factors, were both reduced after coarctation (P <.005 vs controls). There was increased BrdU incorporation at 3 days and 1 and 2 weeks (P <.001 vs controls). There were no remarkable changes in the apoptosis rate until 4 weeks later. CONCLUSION: Cell proliferation was stimulated at 3 days, and apoptosis was halted until 4 weeks. These changes were associated with upregulation of TGF-beta and downregulation of Bcl-xS and Fas ligand gene expression. These findings suggest that a coordinated regulation of cell proliferation and cell death contributes to arterial remodeling in response to acute sustained elevation of blood pressure. Cell proliferation precedes apoptosis by 2 weeks in this procedure.
OBJECTIVE: The molecular basis of vascular response to hypertension is largely unknown. Both cellular and extracellular components are critical. In the current study we tested the hypothesis that there is a balance between vascular cell proliferation and cell death during vessel remodeling in response to hypertension. METHODS: A midthoracic aortic coarctation was created in rats to induce an elevation of blood pressure proximal to the coarctation. The time course was 1 and 3 days and 1, 2, and 4 weeks for the study of the proximal aorta. Ribonuclease protection assay and Western blot analysis were used to evaluate gene expression of growth and apoptosis-related cytokines with two sets of multiple probes, rCK-3 and rAPO-1. Cell proliferation was determined with BrdU (5-bromo-2'-deoxyuridine) incorporation. Apoptosis was examined with TUNEL (transferase-mediated dUTP nick end-labeling). Morphometry was performed on histologic sections. RESULTS:Coarctation produced hypertension in the proximal aorta, 118 +/- 9 mm Hg versus 94 +/- 6 mm Hg in controls (P <.002). Both messenger RNA and protein levels of transforming growth factor (TGF)-beta1 and TGF-beta3 were increased (P <.005 vs controls). Messenger RNA and protein of Bcl-xS and Fas ligand, known as proapoptotic factors, were both reduced after coarctation (P <.005 vs controls). There was increased BrdU incorporation at 3 days and 1 and 2 weeks (P <.001 vs controls). There were no remarkable changes in the apoptosis rate until 4 weeks later. CONCLUSION: Cell proliferation was stimulated at 3 days, and apoptosis was halted until 4 weeks. These changes were associated with upregulation of TGF-beta and downregulation of Bcl-xS and Fas ligand gene expression. These findings suggest that a coordinated regulation of cell proliferation and cell death contributes to arterial remodeling in response to acute sustained elevation of blood pressure. Cell proliferation precedes apoptosis by 2 weeks in this procedure.
Authors: M Guzmán-Fulgencio; J Berenguer; M García-Álvarez; D Micheloud; J C López; J Cosín; I Fernández de Castro; P Catalán; P Miralles; S Resino Journal: Eur J Clin Microbiol Infect Dis Date: 2011-03-26 Impact factor: 3.267
Authors: Jin-Jia Hu; Andy Ambrus; Theresa W Fossum; Matthew W Miller; Jay D Humphrey; Emily Wilson Journal: J Histochem Cytochem Date: 2007-12-10 Impact factor: 2.479
Authors: Mohamad Azhar; Jo El J Schultz; Ingrid Grupp; Gerald W Dorn; Pierre Meneton; Daniel G M Molin; Adriana C Gittenberger-de Groot; Thomas Doetschman Journal: Cytokine Growth Factor Rev Date: 2003-10 Impact factor: 7.638