NYMC Faculty Publications

The Camp/PKA Signaling Pathway Conditions Cardiac Performance in Experimental Animals With Metabolic Syndrome

Author Type(s)

Student, Faculty

DOI

10.1016/j.yjmcc.2024.09.002

Journal Title

Journal of Molecular and Cellular Cardiology

First Page

35

Last Page

51

Document Type

Article

Publication Date

11-1-2024

Department

Medicine

Second Department

Cell Biology and Anatomy

Third Department

Pathology, Microbiology and Immunology

Keywords

Cell mechanics, Metabolic syndrome, Myocytes, Obesity

Disciplines

Medicine and Health Sciences

Abstract

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.

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