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The Contribution of Phosphodiesterases to Cardiac Dysfunction in High Carbohydrate Diet-Induced Metabolic Syndrome Rats.

08:00 EDT 12th July 2019 | BioPortfolio

Summary of "The Contribution of Phosphodiesterases to Cardiac Dysfunction in High Carbohydrate Diet-Induced Metabolic Syndrome Rats."

Metabolic syndrome (MetS) is a cluster of risk factors such as insulin resistance among others, underlying the development of diabetes and/or cardiovascular diseases. Studies show a close relationship between cardiac dysfunction and abnormal cAMP catabolism, contributing to pathological-remodeling. Taken into consideration the importance of therapeutic enhancement of cAMP by stimulating its synthesis via suppression of PDEs, we examined their roles on cardiac dysfunction in high carbohydrate diet-induced MetS-rats. We first demonstrated significantly high expression levels of PDE3 and PDE4, the most highly expressed subtypes, together with the depressed cAMP-level in heart-tissue from MetS-rats. Second, we demonstrated these PDEs activities by using either their basal or PDE inhibitor-induced intracellular levels of cAMP and Ca2+, the transient intracellular Ca2+ changes under electrical-stimulation, isometric contractions in papillary muscle strips and some key signaling proteins (such as RyR2, PLN, PP1A and PKA) responsible for the Ca2+ homeostasis in isolated cardiomyocytes from MetS-rats. Overall, our present data demonstrated that the clear recovery in decreased basal cAMP level, increased protein expression levels of PDE3 and PDE4 as well as positive responses in the altered Ca2+ homeostasis to PDEs inhibitors can provide important insights on the roles of activated PDEs in depressed contractile activity of hearts from MetS-rats.

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This article was published in the following journal.

Name: Canadian journal of physiology and pharmacology
ISSN: 1205-7541
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