title: Phosphodiesterase 3A1 protects the heart against angiotensin II-induced cardiac remodeling through regulation of transforming growth factor-β expression.
abstract: Accumulating evidence suggests that there are direct interactions between β-adrenergic and angiotensin II signaling pathways, and β-blockers protect the heart against angiotensin II-induced cardiac remodeling. Phosphodiesterase 3A (PDE3A) regulates β-adrenergic receptor/protein kinase A signaling by metabolizing cAMP. Therefore, we hypothesized that overexpressed PDE3A has cardioprotective effects against angiotensin II-induced cardiac remodeling by regulating angiotensin II signaling. In the present study, we used transgenic mice with cardiac-specific overexpressed PDE3A1. We showed that continuous administration of angiotensin II caused cardiac hypertrophy in the wild-type mouse heart, but not in the transgenic mouse heart. Angiotensin II induced cardiac fibrosis in both wild-type and transgenic mice, but the extent of fibrosis was less in transgenic mice compared to wild-type mice. Moreover, basal expression levels of transforming growth factor-β were lower in transgenic mouse hearts, and it remained at lower levels after angiotensin II stimulation. These findings suggest that PDE3A protects the heart from angiotensin II-induced cardiac remodeling through its modulation of the functional connection between angiotensin II and transforming growth factor-β.
authors.affiliation: Department of Cardiology and Hematology, Fukushima Medical University.
authors.forename: Shoji
authors.initials: S
authors.lastname: Iwaya
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Oikawa
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.forename: Yasuchika
authors.initials: Y
authors.lastname: Takeishi
mesh_terms: D000804:Angiotensin II / Q000633:toxicity*; D000818:Animals; D015153:Blotting, Western; D002312:Cardiomyopathy, Hypertrophic / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3 / Q000096:biosynthesis*; D004195:Disease Models, Animal; D004452:Echocardiography; D006352:Heart Ventricles / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*; D014662:Vasoconstrictor Agents / Q000633:toxicity; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D016212:Transforming Growth Factor beta; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3