The cAMP/PKA signaling pathway conditions cardiac performance in experimental animals with metabolic syndrome.

Autor: Pizzo E; Department of Physiology, New York Medical College, Valhalla, NY, USA., Cervantes DO; Department of Physiology, New York Medical College, Valhalla, NY, USA., Ripa V; Department of Physiology, New York Medical College, Valhalla, NY, USA., Filardo A; Department of Physiology, New York Medical College, Valhalla, NY, USA., Berrettoni S; Department of Physiology, New York Medical College, Valhalla, NY, USA., Ketkar H; Department of Pathology, Microbiology and Immunology, New York Medical College, Valhalla, NY, USA., Jagana V; Department of Cell Biology and Anatomy, New York Medical College, Valhalla, NY, USA., Di Stefano V; Department of Physiology, New York Medical College, Valhalla, NY, USA., Singh K; Department of Physiology, New York Medical College, Valhalla, NY, USA., Ezzati A; Department of Physiology, New York Medical College, Valhalla, NY, USA., Ghadirian K; Department of Physiology, New York Medical College, Valhalla, NY, USA., Kouril A; Department of Physiology, New York Medical College, Valhalla, NY, USA., Jacobson JT; Department of Physiology, New York Medical College, Valhalla, NY, USA; Department of Cardiology, Westchester Medical Center, Valhalla, NY, USA., Bisserier M; Department of Physiology, New York Medical College, Valhalla, NY, USA; Department of Cell Biology and Anatomy, New York Medical College, Valhalla, NY, USA., Jain S; Department of Pathology, Microbiology and Immunology, New York Medical College, Valhalla, NY, USA., Rota M; Department of Physiology, New York Medical College, Valhalla, NY, USA. Electronic address: marcello_rota@nymc.edu.
Jazyk: angličtina
Zdroj: Journal of molecular and cellular cardiology [J Mol Cell Cardiol] 2024 Nov; Vol. 196, pp. 35-51. Date of Electronic Publication: 2024 Sep 07.
DOI: 10.1016/j.yjmcc.2024.09.002
Abstrakt: Metabolic syndrome (MetS) increases the risk of coronary artery disease, but effects of this condition on the working myocardium remain to be fully elucidated. In the present study we evaluated the consequences of diet-induced metabolic disorders on cardiac function and myocyte performance using female mice fed with Western diet. Animals maintained on regular chow were used as control (Ctrl). Mice on the Western diet (WesD) had increased body weight, impaired glucose metabolism, preserved diastolic and systolic function, but increased left ventricular (LV) mass, with respect to Ctrl animals. Moreover, WesD mice had reduced heart rate variability (HRV), indicative of altered cardiac sympathovagal balance. Myocytes from WesD mice had increased volume, enhanced cell mechanics, and faster kinetics of contraction and relaxation. Moreover, levels of cAMP and protein kinase A (PKA) activity were enhanced in WesD myocytes, and interventions aimed at stabilizing cAMP/PKA abrogated functional differences between Ctrl and WesD cells. Interestingly, in vivo β-adrenergic receptor (β-AR) blockade normalized the mechanical properties of WesD myocytes and revealed defective cardiac function in WesD mice, with respect to Ctrl. Collectively, these results indicate that metabolic disorders induced by Western diet enhance the cAMP/PKA signaling pathway, a possible adaptation required to maintain cardiac function.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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