Background: The mechanisms involved in the biggest remodeling caused by the post-infarct beta-carotene are unknown.

Radiolabeled CRIP allows for noninvasive visualization of interstitial alterations during cardiac remodeling, and is responsive to antiangiotensin treatment. If proven clinically feasible, such a strategy would help identify post-MI patients likely to develop heart failure.

The outcome of infarct healing in mice strongly depends on genetic background. On the basis of our results, we suggest that for studies on infarct rupture, the 129S6 mouse is the background of choice, whereas BalbC and Swiss mice are the preferred models to study infarct thinning post-MI.

No abstract

Abstract-The hypertrophic response of the heart has been recognized recently as the net result of activation of prohypertrophic and antihypertrophic pathways. Here we report the involvement of the Wnt/Frizzled pathway in the onset of cardiac hypertrophy development. Stimulation of the Wnt/Frizzled pathway activates the disheveled (Dvl) protein. Disheveled subsequently can inhibit glycogen synthase kinase-3␤, a protein with potent antihypertrophic actions through diverse molecular mechanisms. In the Wnt/Frizzled pathway, inhibition of glycogen synthase kinase-3␤ leads to an increased amount of ␤-catenin, which can act as a transcription factor for several hypertrophy-associated target genes. In this study we subjected mice lacking the Dvl-1 gene and their wild-type littermates to thoracic aortic constriction for 7, 14, and 35 days. In mice lacking the Dvl-1 gene, 7 days of pressure overload-induced increases in left ventricular posterior wall thickness and expression of atrial natriuretic factor and brain natriuretic protein were attenuated compared with their wild-type littermates. ␤-Catenin protein amount was reduced in the group lacking the Dvl-1 gene, and an increased glycogen synthase kinase-3␤ activity was observed. Moreover, the increase in the amount of Ser 473 -phosphorylated Akt, a stimulator of cardiac hypertrophy, was lower in the group lacking the Dvl-1 gene.In conclusion, we have demonstrated that interruption of Wnt signaling in the mice lacking the Dvl-1 gene attenuates the onset of pressure overload-induced cardiac hypertrophy through mechanisms involving glycogen synthase kinase-3␤ and Akt. Therefore, the Wnt/Frizzled pathway may provide novel therapeutic targets for antihypertrophic therapy. Key Words: hypertrophy Ⅲ Wnt Ⅲ cell signaling Ⅲ glycogen synthase kinase-3␤ Ⅲ Akt C ardiac hypertrophy is an adaptive response of the heart to an increased workload, caused by a variety of pathological stimuli, including hypertension, myocardial infarction, and valvular disease. Because cardiomyocytes are terminally differentiated, these cells can only respond by hypertrophic growth. 1 This growth is initially beneficial but a sustained hypertrophic response often leads to heart failure. 2 In this hypertrophic response, extracellular stimulation is translated into a cellular response, leading to changes in the contractile apparatus and to an activation of many signaling pathways. 3 Several of these signaling pathways transduce prohypertrophic signals, but it has been shown that a number of endogenous molecules can regulate the hypertrophic response negatively. 4 One of the most powerful negative regulators that can antagonize the hypertrophic response is glycogen synthase kinase-3␤ (GSK-3␤), a ubiquitous serine/threonine protein kinase. 4,5 GSK-3␤ is a downstream regulatory switch of multiple signaling pathways that regulates a wide range of cellular functions. 6 Dysregulation of GSK-3␤ plays a role in many human diseases, including diabetes, Alzheimer's disease, bipolar disorder, cancer, 7 and heart failur...

Radiolabeled CRIP allows for the evaluation of the efficacy of neurohumoral antagonists after MI and reconfirms superiority of combination therapy. If proven clinically, molecular imaging of the myocardial healing process may help plan an optimal treatment for patients susceptible to heart failure.

The data show a reduced expression and defective localization of alphaE-catenin in the intercalated disc region in patients dying of infarct rupture. The mechanism of lower expression of alphaE-catenin remains to be elucidated.

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