Murine cardiac growth, TRPC channels, and cGMP kinase I

作者：Domes Katrin; Patrucco Enrico; Loga Florian; Dietrich Alexander; Birnbaumer Lutz; Wegener Joerg W; Hofmann Franz^*

来源：Pflugers Archiv-European Journal of Physiology, 2015, 467(10): 2229-2234.

DOI：10.1007/s00424-014-1682-0

• Cardiac myocytes
• Endothelium/fibrocytes
• Nitric oxide/PKG-I
• Signal transduction
• TRPC channels

Signaling via cGMP-dependent protein kinase I (cGKI) and canonical transient receptor potential (TRPC) channels appears to be involved in the regulation of cardiac hypertrophy. Recent evidence suggests that TRPC channels are targets for cGKI, and phosphorylation of these channels may mediate the antihypertrophic effects of cGMP signaling. We tested this concept by investigating the role of cGMP/cGKI signaling on angiotensin II (A II)-induced cardiac hypertrophy using a control group (Ctr), trpc6(-/-), trpc3(-/-), trpc3(-/-)/6(-/-), beta RM mice, and trpc3(-/-)/6(-/-) x beta RM mice. beta RM mice express cGKI beta only in the smooth muscle on a cGKI(-/-) background. The control group was composed of littermate mice that contained at least one wild type gene of the respective genotype. A II was infused by minipumps (7 days; 2 mg/kg/day) in Ctr, trpc6(-/-), trpc3(-/-), trpc3(-/-)/6(-/-), beta RM, and trpc3(-/-)/6(-/-) x beta RM mice. Hypertrophy was assessed by measuring heart weight per tibia length (HW/TL) and fibrosis by staining of heart slices. A II-induced increase in HW/TL and fibrosis was absent in trpc3 (-/-) mice, whereas an increase in HW/TL and fibrosis was evident in Ctr and trpc6(-/-), minimal or absent in trpc3(-/-), moderate in beta RM, and dramatic in trpc3(-/-)/6(-/-) beta RM mice. These results suggest that TRPC3 may be necessary for A II-induced cardiac hypertrophy. On the other hand, hypertrophy and fibrosis were massively increased in beta RM mice on a TRPC3/6 x cGKI(-/-)KO background, indicating an "additive" coupling between both signaling pathways.

• 出版日期2015-10
• 单位NIH