Paracrine endothelial actions of B-type natriuretic peptide (BNP) and its guanylyl cyclase receptor (GC-A) are critically involved in vascular regeneration (SFB 688)
Christine Siegl, Mirja Hünerberg, Heike Oberwinker, Katharina Völker, Anja Rahaus and Michaela Kuhn
The endothelial GC-A receptor is activated by ANP and BNP. Whereas ANP is mainly produced in cardiac myocytes, BNP additionally is produced in other cell types in response to stressors such as hypoxia. In particular, we observe that satellite cells, which are activated within ischemic skeletal muscle, display BNP immunoreactivity. Our studies in vivo and with cultured endothelial cells indicate that BNP produced by satellite cells proliferating in the postischemic regenerating muscle stimulates the regeneration and migration of neighboring endothelia.
Within the heart, BNP is mainly expressed when pressure overload induces hypertrophy. Cardiac hypertrophy and angiogenesis are coordinately regulated during adaptive cardiac growth, and disruption of the balanced myocyte growth and angiogenesis contributes to heart failure. This coordination is at least partly achieved by the secretion of angiogenic factors from myocytes in response to hypertrophic stimuli. Our experimental studies indicate that BNP is among the proangiogenic genes induced in the early phase of pressure load-induced cardiac hypertrophy.
Kuhn M, Völker K, Schwarz K, Flögel U, Jacoby C, Stypmann J, van Eickels M, Gambaryan S, et al. (2009) The natriuretic peptide / guanylyl cyclase-A system functions as a stress-responsive regulator of angiogenesis in mice. J Clin Invest 119:2019-2030.