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In renovascular hypertension, angiotensin II leads to an elevation of blood pressure and to cardiac hypertrophy. The fibroblast growth factor-2 (FGF-2) has been implicated in cardiomyocyte growth. Therefore, we investigated whether FGF-2 could control the development of angiotensin II-induced cardiac hypertrophy. Mice deficient for the expression of FGF-2 were created, and the role of FGF-2 was investigated in the two kidney-one clip (2K1C) model of renin-dependent hypertension. The activation of the MAPK pathways were shown to be crucial in the intracellular signaling leading to cardiac hypertrophy. Therefore, we followed also the cardiac activation of JNK, ERK and the p38 kinase in these animals. Both wild-type and FGF-2 deficient (FGF-2 -/-) mice showed similar elevation of blood pressure in the 2K1C model. Interestingly, 2K1C FGF-2 -/- mice developed markedly reduced hypertrophy as compared to wild-types. Moreover, in 2K1C wild-types, cardiac hypertrophy developed in association with a concomitant stimulation of JNK, ERK and p38. In contrast, JNK activation was strongly decreased in hypertensive mice deficient for FGF-2, while p38 and ERK were less affected. These data suggest that FGF-2 is important in mediating angiotensin II-induced cardiac hypertrophy in renovascular hypertension via autocrine/paracrine mechanisms.
Membrane-Type 1 Matrix Metalloproteinase Downregulates Fibroblast Growth Factor-2 Binding to the Cell Surface and Intracellular Signaling