Differential role of g protein-coupled receptor Kinase 5 in physiological versus pathological cardiac hypertrophy

RATIONALE: G protein-coupled receptor (GPCR) kinases (GRKs) are dynamic regulators of cellular signaling. GRK5 is highly expressed within myocardium and is up-regulated in heart failure (HF). Although GRK5 is a critical regulator of cardiac GPCR signaling, recent data has uncovered non-canonical activity of GRK5 within nuclei that plays a key role in pathological hypertrophy. Targeted cardiac elevation of GRK5 in mice leads to exaggerated hypertrophy and early HF after transverse aortic constriction (TAC) due to GRK5 nuclear accumulation. OBJECTIVE: In this study we investigated the role of GRK5 in physiological, swimming induced hypertrophy (SIH). METHODS AND RESULTS: Cardiac-specific GRK5 transgenic mice (TgGRK5) and non-transgenic littermate control (NLC) mice were subjected to a 21-day high intensity swim protocol (or no swim sham controls). SIH and specific molecular and genetic indices of physiological hypertrophy were assessed including nuclear localization of GRK5 and compared to TAC. Unlike after TAC, swim-trained TgGRK5 and NLC mice exhibited similar increases in cardiac growth. Mechanistically, SIH did not lead to GRK5 nuclear accumulation, which was confirmed in vitro as insulin-like growth factor-1, a known mediator of physiological hypertrophy, was unable to induce GRK5 nuclear translocation in myocytes. We found specific patterns of altered gene expression between TAC and SIH with GRK5 overexpression. Further, SIH in post-TAC TgGRK5 mice was able to preserve cardiac function. CONCLUSIONS: These data suggest that while nuclear-localized GRK5 is a pathological mediator after stress, this non-canonical nuclear activity of GRK5 is not induced during physiological hypertrophy

Differential role of g protein-coupled receptor Kinase 5 in physiological versus pathological cardiac hypertrophy

Corals in the Eastern Pacific extend south from the Gulf of California to Ecuador and oceanic Chile, and west from Colombia to Clipperton Atoll. Nevertheless, large stretches of the Mexican Pacific remain fundamentally unstudied. Therefore, to assess the current conditions of coral communities, a coastal fringe ?300km long (17�40?N, 101�39?W to 16�46?N, 99�49?W) was surveyed within the Southern Mexican Pacific, between 2005 and 2009. Fifteen stony coral species were identified at 13 coral communities and six Pocillopora-dominated fringing reefs, with Pocillopora verrucosa and Pocillopora damicornis the primary contributing taxa. Reef development was identified in embayments or behind rocks or islands that offered shelter from northern and northwestern winds. Observations of Pocillopora effusus, Pocillopora inflata, Porites lobata, Pavona clavus, and Pavonavarians expanded the species known geographic ranges by several degrees of latitude, suggesting reef building fauna comprised a mixture of widespread and relatively rare Eastern Pacific corals. Results indicated greater live coral cover in the Ixtapa-Zihuatanejo area (15-73%) than in the Acapulco localities, which had high algal dominance; the reefs in the latter region exhibited high erosion. Regional differences are likely the result of long-standing anthropogenic pressures around Acapulco since 1950, when it became an important tourist destination. This paper is the first detailed report of ecologically stressed corals and coral reefs from the state of Guerrero on the Mexican Southern Pacific coast. � 2012 Blackwell Verlag GmbH