Role of Pin1 in Cardiac Hypertrophy (p 1244)
Ramping up, or reducing, Pin1 activity attenuates cardiac hypertrophy, report Toko et al.
The Ser-Pro and Thr-Pro motifs in proteins are recognized and phosphorylated by proline-directed kinases such as Akt and MEK. These phosphorylation events are like light switches that can turn the target proteins on or off. But, the lights can also be dimmed or brightened by Pin1, a small protein that binds to phosphorylated Ser-Pro and Thr-Pro and adjusts the intensity of activation or repression. Pin-1 thus fine tunes a variety of cellular signaling pathways. However, little is known of the protein's activity in cardiomyocytes. Toko and colleagues discovered that Pin1 is highly expressed in the newborn mouse heart, but that its expression decreases by almost half as mice age. An exception to this phenomenon was pressure overload, when the expression of Pin1 was increased dramatically. Investigating, how different levels of Pin1 affected pressure-induced hypertrophy, the team found that mice lacking Pin1 maintained better cardiac function, exhibited fewer signs of hypertrophy and were more likely to survive following pressure overload than their wild type counterparts. Surprisingly over-expression of Pin1 also attenuated hypertrophy. The team deciphered that both under and over-expression of Pin1, via different pathways, reduced the activity of MEK—a known instigator of hypertrophy. Tweaking Pin1 balance in either direction might be beneficial in treating hypertrophy, say the authors.
Relationship Among Cardiogenic Progenitor Cells (p 1253)
Dey et al identify differences between cardiogenic progenitor cells.
Accumulating evidence suggests that the heart does not solely consist of terminally differentiated cells, but that it could also undergo regeneration. Indeed, a number of cardiogenic cell types have been discovered in the heart and in the bone marrow. The existence of these cells has sparked excitement regarding their potential use in reparative therapies. But whether these cardiogenic cells are in anyway related to one another has not been established. Dey et al isolated three populations of mouse progenitor cells from the heart—ckit+, Sca1+ and SP—and two from the bone marrow—ckit+ and MSCs. They extracted RNA from each and compared their transcriptional profiles. They found that cardiac-derived progenitors and bone marrow-derived progenitors were very different from each other, with the cardiac-derived cells tending to express higher levels of matrix and cell-to-cell attachment factors, and the bone marrow cells expressing higher levels of cell cycle factors. Even the two ckit+ populations differed substantially. Of the three cardiac populations, the team determined that Sca1+ cells were the most closely related to differentiated cardiomyocytes, while the ckit+ cells were the most primitive, suggesting the three progenitor types might represent distinct differentiation stages. The improved understanding progenitor population relatedness should help in designing future cardiac repair strategies, say the authors.
Adiponectin and Muscle Insulin Delivery/Action (p 1263)
Zhao et al figure out how adiponectin improves the action of insulin in muscle.
The hormone adiponectin circulates in the blood and is known to enhance insulin action. Indeed, low plasma levels of adiponection are associated with insulin resistance and diabetes in humans and mice, while replenishing adiponectin levels in mice improves insulin sensitivity. Adiponectin also promotes nitric oxide production in endothelial cells, and thus induces vasodilation. Now Zhao and colleagues show that it is this vasodilatory activity that enables adiponectin to improve insulin sensitivity. They found that injecting rats with adiponectin increases plasma nitric oxide levels, consequently increasing blood volume in the hindlimb skeletal muscle. Insulin uptake into the muscle also increased as did the rate of whole-body glucose disposal in response to insulin administration. These effects of adiponectin were blocked by inhibiting nitric oxide synthase—the enzyme responsible for producing nitric oxide—confirming that vasodilation was required for the increased insulin sensitivity. The authors explained that vasodilation expands the endothelial exchange surface for uptake of insulin, and suggest that targeting the muscle vasculature and hypoadiponectinemia could be important for the prevention and treatment of insulin-resistance and type 2 diabetes.
- © 2013 American Heart Association, Inc.